Early Diagnosis of Familial Nephropathy

in English Cocker Spaniels

Two litters of English cocker spaniels (ECSs) produced by familial nephropathy (FN)
carriers were evaluated to characterize the early features of this disease. Three
puppies developed FN. Proteinuria, which began when these puppies were five-to-
eight months old, was the first abnormality detected. Proteinuria persisted while each
puppy’s growth rate slowed, and renal function gradually deteriorated. The interval
from onset of proteinuria to development of azotemia was two-to-nine months.
Characteristic glomerular capillary basement membrane (GCBM) lesions were seen
with transmission electron microscopy (TEM) of renal biopsy specimens obtained
during this interval. Ultrastructural GCBM lesions progressed substantially during the
interval from biopsy to necropsy. However, routine light microscopic findings did not
allow definitive diagnosis of FN in either biopsy or necropsy specimens.
Detection of FN can be accomplished by screening at-risk ECSs for
proteinuria. Renal biopsies are required to confirm the diagnosis in dogs for which
proteinuria cannot be explained otherwise. Percutaneous needle biopsy specimens
sufficient for TEM must be used to examine the GCBM to make a definitive
diagnosis. J Am Anim Hosp Assoc 1998;34:189–95.

George E. Lees, DVM, MS Introduction

R. Gayman Helman, DVM, PhD
Linda D. Homco, DVM
Nicholas J. Millichamp,
BVet Med, PhD
Jon F. Hunter, DVM, MS
Miles S. Frey, BS
O and one female) ECSs; they were the first well-documented cases
An inherited renal disease, first called renal cortical hypoplasia, has
been recognized in English cocker spaniels (ECSs) for more than 40
years. 1–3 When investigators recognized that the primary renal lesion
was not cortical hypoplasia, familial nephropathy (FN) became the
preferred name for the disorder. 4–7 In ECSs, FN is inherited as an
autosomal recessive trait. 6 The age at onset of illness in most dogs is
six-to-24 months.8,9 Clinical signs may include polyuria, polydipsia,
weight loss, inappetence, vomiting, or diarrhea. However, affected
dogs may have few signs before the onset of severe renal failure.8 The
disease is progressive and invariably fatal.8,9
Familial nephropathy was diagnosed recently in four (three male
identified in ECSs from North America.10 These FN-affected dogs
were 11-to-27 months old when they were euthanized because of
advanced, chronic renal failure. Renal disease generally was not
detected until it had progressed to a near-terminal stage; a diagnosis
of FN was not confirmed until postmortem studies were performed.

From the Departments of Small Animal Medicine and Surgery (Lees,

Millichamp), Veterinary Pathobiology (Helman, Frey), Large Animal Medicine
and Surgery (Homco), and Veterinary Physiology and Pharmacology (Hunter),
Texas Veterinary Medical Center, Texas A&M University, College Station,
Texas 77843.

Doctor Helman’s current address is Oklahoma Animal Disease Diag-

nostic Laboratory, Oklahoma State University, Stillwater, Oklahoma 74078.

Address reprint requests to Dr. George E. Lees, Department of Small Animal

Medicine and Surgery, College of Veterinary Medicine, Texas A&M University,
College Station, Texas 77843-4474.

JOURNAL of the American Animal Hospital Association 189

190 JOURNAL of the American Animal Hospital Association
Figure 1—Pedigrees of two litters of English cocker spaniels
(dogs designated A–D) produced by familial nephropathy (FN)
carriers. Parents of each litter produced at least one FN-
affected puppy in a previous litter.
Using transmission electron microscopy (TEM),
distinctive ultrastructural changes were observed in
the glomerular capillary basement membranes (GCBMs)
of FN-affected ECSs. 10 Similar GCBM lesions are
used to identify hereditary nephritis (HN) in hu-
mans, 11,12 Samoyeds, 13,14 and bull terriers. 15 There-
fore, the authors concluded that FN in ECSs also is a
form of canine HN.10 Hereditary nephritis refers to a
group of genetic disorders of basement membrane
(type IV) collagen that cause progressive glomerular
disease. 12
In this report, the early features and progression of
FN in ECSs are described. Detection of persistent
proteinuria should prompt evaluation of renal biopsy
samples to confirm FN in young ECSs, because pro-
teinuria is an early abnormality in ECSs with FN 2,8,9
and other dogs with other forms of HN. 16,17
Materials and Methods
The authors evaluated two litters produced by
rebreeding pairs of ECSs that previously produced at
least one FN-affected dog. One litter consisted of a
single male puppy (dog A), and the other litter con-
sisted of two female (dogs B and C) puppies and one
male (dog D) puppy. Thus, four puppies (two males,
two females) that were the progeny of known carriers
of FN [Figure 1] were subjects of this study.
The puppies lived in private homes as pets of their
original or adoptive owners. The original owner of
May/June 1998, Vol. 34
dog A became so attached to the puppy that she kept
it. Puppies from the other litter were donated for
study shortly after they were weaned. Each puppy
was placed in a different local home. New owners
were employees of the College of Veterinary Medi-
cine; they adopted the puppies after being informed
of the planned evaluation schedule, the procedures to
be performed, and the risk (25%) that the puppies
might have FN. Breeders and owners were advised
that affected dogs would be euthanized for postmor-
tem studies before their renal disease became so ad-
vanced that it might cause clinical illness.
The socialization and husbandry of each puppy
were typical of pets kept in its respective household.
Puppies were fed appropriate rations for growing dogs
until renal disease was identified in affected dogs or
until unaffected dogs were one year of age. Dietary
modifications were made when certain illnesses were
discovered. Normal dogs older than one year were fed
a maintenance ration. Routine preventive veterinary
care was provided. A conventional schedule of vacci-
nations was followed, intestinal and external parasite
infestations were treated as needed, and a monthly
heartworm preventative a was given. Additionally, ap-
propriate veterinary care was provided for spontane-
ous illness.
Evaluations were initiated when the puppies were
three months old and were repeated at monthly inter-
vals until each dog was euthanized or reached at least
two years of age. Every month, a physical examina-
tion was performed, and urine was obtained by
cystocentesis for laboratory tests. At three-month in-
tervals, a battery of routine hematological and serum
chemistry tests were performed, and renal ultrasono-
graphic examinations were conducted. Ophthalmic
examinations, indirect blood pressure determinations,
and brain stem auditory-evoked response (BAER)
tests were evaluated every six months. Renal biopsies
also were performed when the dogs were six months,
12-to-13 months, and 24-to-30 months of age. The
age at which affected dogs were euthanized depended
on the rate of deterioration of their renal function;
euthanasia was performed when mild, persistent
azotemia (i.e., serum creatinine greater than 2.0 mg/dl)
developed.
All special clinical evaluations were performed by
qualified investigators. One individual (Lees) per-
formed all physical examinations and provided gen-
eral veterinary care. A veterinary ophthalmologist
(Millichamp) performed ocular examinations using a
slit-lamp biomicroscope and an indirect ophthalmo-
scope following dilatation of the pupils. Arterial blood
pressures were measured indirectly using the oscillo-
metric technique. b Renal ultrasonographic examina-
tions were performed (Homco) using a 7.5-MHZ
mechanical sector transducer. c The BAER test re-
May/June 1998, Vol. 34
Figure 2—Urine protein:creatinine (UP:C) ratios during the first
year of life of four English cocker spaniels at risk for develop-
ment of familial nephropathy (FN). Three FN-affected puppies
(dogs A–C) developed proteinuria, while one unaffected puppy
(dog D) did not (N.R.=normal range, UP:C of 1.0 or less).
cordings were obtained from awake dogs using a stan-
dard protocol.18
Hematological and serum chemistry tests were per-
formed using standard methods. Urinalyses included
standard macroscopic and microscopic tests. Urine
protein:creatinine (UP:C) ratios also were determined.
For UP:C ratios, protein concentrations were deter-
mined by a turbidometric method, d and creatinine
concentrations were measured by an enzymatic
method. e For quantitative aerobic cultures, urine
specimens were inoculated routinely on cystine lac-
tose electrolyte-deficient agar and blood agar plates
using volume-calibrated loops.
Renal specimens were obtained using an ultra-
sonographic-guided, percutaneous needle biopsy
technique during general anesthesia (induced by in-
travenous injection of thiopental sodium and main-
tained with halothane and oxygen). An 18-gauge,
automated biopsy device f with an 11-mm specimen
notch was used. This instrument’s relatively short
depth of penetration aided efforts to keep the entire
biopsy tract in the renal cortex, which was the site of
interest; however, a single biopsy with this device did
not provide sufficient tissue for all intended patho-
logical studies. Therefore, on each occasion when a
renal biopsy was performed, three-to-six samples were
obtained. Using different aspects (i.e., lateral cortex
and both poles) of both kidneys, as needed, serial
needle biopsy samples were obtained at new sites.
Renal biopsy samples were fixed immediately.
When postmortem studies were performed, renal
specimens were fixed within 15 minutes. For light
microscopy, tissues were fixed in 10% buffered for-
malin and embedded in paraffin, sectioned at approxi-
mately 3 µm, and stained with hematoxylin and eosin
(H&E), periodic-acid Schiff (PAS), and trichrome stains.
Postmortem studies included a comprehensive necropsy
performed by a veterinary pathologist (Helman).
Familial Nephropathy 191
For TEM, minced samples of renal cortex were
fixed overnight at 4˚ C in 4% paraformaldehyde and
6.25% glutaraldehyde in 0.1 M sodium cacodylate
buffer with 0.05% calcium chloride (pH, 7.4). Tis-
sues then were washed three times with 0.1 M sodium
cacodylate buffer and further fixed for two hours at 4˚
C in 1% osmium tetroxide with 0.1 M sodium cac-
odylate buffer. Tissues again were washed three times
with 0.1 M sodium cacodylate buffer and then three
times with distilled water before en bloc staining by
overnight immersion at 4˚ C in a saturated uranyl
acetate solution. Tissues were dehydrated in a graded
ethanol series and propylene oxide and were embed-
ded in epoxy resin. g Thick (0.5 µm) sections stained
with toluidine blue were examined to identify por-
tions containing glomerular structures of interest, and
blocks were trimmed accordingly. Thin (60-to-90 nm)
sections then were cut, mounted on copper grids,
stained with uranyl acetate and lead citrate (12 min
each), and examined with a transmission electron
microscope.h
Results
Three of the four puppies in this study eventually
developed FN. They were euthanized shortly after
becoming azotemic. Renal function of the fourth dog
remained normal throughout the study period, which
ended when he was 30 months old.
Proteinuria was the first abnormality detected in
affected puppies. At three months of age, two of the
four puppies had small amounts of protein in their
urine (UP:C, 1.6). However, because proteinuria was
not detected in these two puppies at the next evalua-
tion, the initial finding of mild proteinuria was inter-
preted as not significant. During the remainder of the
study, proteinuria was considered to be clinically in-
significant in young puppies unless it was both sub-
stantial (i.e., UP:C, greater than 2.0) and sustained
(i.e., found subsequently in additional specimens). In
two (dogs A, B) of three affected puppies, sustained
proteinuria first was observed at five months of age.
Onset of proteinuria was recognized in the third puppy
(dog C) when she was eight months old [Figure 2].
A similar pattern of abnormalities was observed in
all affected puppies once they developed proteinuria,
although the timing and rate of subsequent changes
differed in individual puppies. Dog A [Figure 3] had
adequate urine concentrating ability when proteinuria
first was observed at five months of age. However,
during the next two months, urine specific gravity
values decreased progressively while serum creati-
nine values increased gradually. The puppy’s growth
rate slowed following onset of persistent proteinuria.
Proteinuria also began at five months of age in dog
B [Figure 4]; however, the magnitude of proteinuria
did not increase as quickly as it did in dog A. The
192 JOURNAL of the American Animal Hospital Association
Figure 3—Urine protein:creatinine (U-Prot) ratios, body weights,
urine specific gravity values (U-Conc), and serum creatinine
concentrations in an English cocker spaniel puppy (dog A) with
familial nephropathy (N.R.=normal range [UP:C of 1.0 or less;
serum creatinine of 2.0 or less]; good concentration=urine
specific gravity of 1.035 or greater).
Figure 4—Urine protein:creatinine (U-Prot) ratios, body weights,
urine specific gravity values (U-Conc), and serum creatinine
concentrations in an English cocker spaniel puppy (dog B) with
familial nephropathy (N.R.=normal range [UP:C of 1.0 or less;
serum creatinine of 2.0 or less]; good concentration=urine
specific gravity of 1.035 or greater).
peak UP:C ratio in dog B occurred at eight months of
age, whereas the peak UP:C ratio noted in dog A
occurred at six months of age. Emergence of pro-
teinuria in dog B also was associated with subopti-
mum growth. During subsequent months, urine
specific gravity values diminished and serum creati-
nine values increased. However, serum creatinine did
not increase as quickly in dog B as it did in dog A.
Azotemia (serum creatinine, greater than 2.0 mg/dl)
did not develop in dog B until she was 12 months old.
In dog C [Figure 5], both onset and the peak mag-
nitude of proteinuria occurred several months later
than in dog B. However, as with the other proteinuric
ECS puppies, onset of proteinuria was associated with
reduced rate of growth. Adequate urine concentrating
ability was observed initially, but urine specific grav-
ity values decreased while proteinuria persisted.
Azotemia gradually developed at 17 months of age.
Thus, affected puppies had persistent proteinuria
associated with slowing of growth rate, followed by
May/June 1998, Vol. 34
Figure 5—Urine protein:creatinine (U-Prot) ratios, body weights,
urine specific gravity values (U-Conc), and serum creatinine
concentrations in an English cocker spaniel puppy (dog C) with
familial nephropathy (N.R.=normal range [UP:C of 1.0 or less;
serum creatinine of 2.0 or less]; good concentration=urine
specific gravity of 1.035 or greater).
Figure 6—Urine protein:creatinine (U-Prot) ratios, body weights,
urine specific gravity values (U-Conc), and serum creatinine
concentrations in a normal English cocker spaniel puppy (dog
D) (N.R.=normal range [UP:C of 1.0 or less; serum creatinine of
2.0 or less]; good concentration=urine specific gravity of 1.035
or greater).
progressive deterioration of renal function, manifested
first by diminishing urine concentration and then by
azotemia. The unaffected dog (dog D) [Figure 6] con-
tinued to grow, had good urine concentrating ability,
and was not azotemic.
Intervals between development of proteinuria and
onset of azotemia were two months (dog A), seven
months (dog B), and nine months (dog C). These inter-
vals provided an opportunity to obtain renal biopsy
specimens for definitive diagnosis of the disease be-
fore azotemia developed. Biopsies taken from six-
month-old proteinuric puppies yielded diagnoses of
FN one month (in dog A) and six months (in dog
B) before onset of azotemia. For dog C, the renal
biopsy taken when she was 13 months old con-
firmed FN four months before she became azo-
temic. Following diagnosis of FN, the diet of each
affected dog was changed to a modified ration con-
taining reduced quantities of protein, sodium, cal-
cium, and phosphorus. i
May/June 1998, Vol. 34
Figure 7—Transmission electron photomicrograph of glomeru-
lar structures in a renal biopsy sample obtained from a six-
month-old English cocker spaniel puppy (dog B) with familial
nephropathy. The glomerular capillary wall separates the cap-
illary lumen (CL) from the urinary space (US). Note mild splitting
and irregular thickening of the glomerular membrane (compare
with Figure 8) (Saturated uranyl acetate and Sato’s lead citrate
stain, 4,660X; bar=1 µm).
Renal biopsies were taken on seven occasions.
Each puppy was biopsied at six months of age, dogs C
and D were biopsied a second time at 13 months of
age, and the unaffected dog (dog D) was biopsied a
third time at 30 months of age. Renal specimens also
were obtained for evaluations when each affected dog
was necropsied. All renal biopsy specimens were ad-
equate for light microscopic examinations; however,
light microscopy did not permit definitive diagnosis
of FN. In two affected puppies (dogs B, C), renal tissues
obtained after they developed proteinuria but before
they developed azotemia were found to be normal. In
the puppy (dog A) with the most rapidly progressive
disease, diffuse glomerular disease was detected by
light microscopy of the biopsy specimen obtained at
six months of age. Glomerular capillary basement
membranes were irregular and segmentally thickened,
but glomerular fibrosis was minimal. Patchy accu-
mulations of lymphocytes, monocytes, and plasma
cells along with a few neutrophils were observed
in the cortical interstitium. Focal areas of fibrosis
were associated with larger areas of interstitial
inflammatory cell infiltrate. Tubular protein casts
were not observed.
Two of seven renal biopsy samples processed for
TEM evaluation did not contain glomeruli. The other
five samples contained glomeruli. In specimens ob-
tained from nonazotemic dogs with proteinuria, thick-
ening and multilaminar splitting of the GCBM were
diffuse [Figure 7]. At this stage of the disease, ultra-
structural GCBM changes were mild but clearly ap-
parent compared with findings for the nonproteinuric
dog [Figure 8]. Renal biopsy samples obtained after
dogs became proteinuric always had ultrastructural
GCBM changes that were typical of FN.
Familial Nephropathy 193
Figure 8—Transmission electron photomicrograph of glomeru-
lar structures in a renal biopsy sample obtained from a normal,
six-month-old English cocker spaniel puppy (dog D). The
glomerular capillary wall separates the capillary lumen (CL)
from the urinary space (US). Thickness of the glomerular
capillary basement membrane is normal, and component layers
of the membrane are uniform (Saturated uranyl acetate and
Sato’s lead citrate stain, 4,660X; bar=1 µm).
Ultrasonographic changes in renal architecture or
echogenicity were not observed before proteinuria
developed in affected dogs. However, the renal cortices
eventually became mildly hyperechoic as the disease
progressed. Increases in renal cortical echogenicity
were not observed until several months after FN was
diagnosed. Thus, although sonography was essential
for renal biopsy, it did not aid early diagnosis of FN.
Affected dogs did not have ocular abnormalities
analogous to those sometimes found in humans with
HN. 12 Each dog’s hearing, tested on at least two occa-
sions, was not impaired. Systemic blood pressures
measured once in dog A, twice each in dogs B and C,
and three times in dog D, were normal.
Early diagnosis of FN helped owners to adapt and
plan for subsequent events. The owner of dog A was
interested in renal transplantation; after FN was diag-
nosed at six months of age, dog A was withdrawn
from the study and taken to another veterinary center.j
Kidney transplantation was performed when he was
seven months old. An episode of acute graft rejection
began 29 days after the transplant was performed.
Treatment of graft rejection was unsuccessful. When
this puppy was eight months old, he was returned to
the authors for euthanasia and necropsy.
Dog B was euthanized and necropsied when she
was 13 months old; dog C was euthanized and necrop-
sied when she was 17 months old. Owners had four-
to-six months to adjust to their dogs’ terminal disease.
Owners participated in selection of the date of eutha-
nasia; this helped them cope with their grief.
At necropsy, the kidneys of affected dogs were
reduced slightly in size. Their cortices were slightly
but uniformly thinned; their cortical to medullary ra-
tios were 0.33 to 0.5. The renal cortices were dif-
194 JOURNAL of the American Animal Hospital Association
Figure 9—Transmission electron photomicrograph of glomeru-
lar structures in a renal sample obtained at necropsy from a 13-
month-old, familial nephropathy-affected English cocker spaniel
(dog B). The glomerular capillary wall separates the capillary
lumen (CL) from the urinary space (US). The degree of glomeru-
lar capillary basement membrane splitting and thickening is
more severe than that observed in the previous biopsy sample
(see Figure 7) (Saturated uranyl acetate and Sato’s lead citrate
stain, 4,660X; bar=1 µm).
fusely pale tan. The renal capsules adhered to the
cortical surfaces at multifocal sites, and the cortical
surfaces were finely pitted. The grafted kidney of dog
A was swollen and diffusely red-black. This puppy
also had hemorrhagic gastroenteritis attributed to
acute uremia that developed after failure of the trans-
planted kidney. In the other two dogs, gross lesions
were observed only in the kidneys.
Sections of kidneys obtained at necropsy had glo-
merular and tubulointerstitial lesions observed by
light microscopy. Lesions observed in dogs B and C
were similar to those seen in dog A at six months of
age; however, the changes were more severe in dogs
B and C. Cortical interstitial disease, especially fi-
brosis, was more diffuse compared with biopsy
samples. Glomerular disease progressed to glomeru-
lar fibrosis with sclerosis and complete obliteration of
some glomeruli. Periglomerular fibrosis also was
present. Proximal tubules contained protein casts. Renal
specimens obtained at necropsy for TEM examination
had diffuse GCBM thickening and splitting that were
more severe than similar changes observed in renal
biopsy specimens obtained two-to-seven months pre-
viously [Figure 9].
An episode of sterile struvite urolithiasis, similar
to that previously described in ECSs,19 occurred in
the unaffected dog (dog D). Urocystoliths were dis-
covered by sonography and radiography when he was
21 months old. Microscopic hematuria first was de-
tected by urinalysis one month previously. On two
occasions, cultures of urine for aerobic bacteria were
sterile. Presumptive diagnosis of sterile struvite uroli-
thiasis was made, and the dog’s diet was changed to a
ration formulated to promote dissolution of such
uroliths. k Uroliths were not detected by ultraso-
May/June 1998, Vol. 34
nograpy one month later. The dog was fed the stone
dissolution diet for one additional month, then the
diet was changed to a maintenance ration. Another
dog living in that household was being fed a specific
diet to control obesity, so both dogs were fed the
same ration. l The dog had no signs of urolithiasis for
the remainder of the study, and uroliths were not
found by ultrasonography when the dog was 30
months old.
Discussion
Two ECS puppies with FN developed proteinuria
when they were five months of age; however, pro-
teinuria was not detected in one affected ECS puppy
until she was eight months of age. Unfortunately, too
few ECSs with FN have been evaluated to state confi-
dently when detectable proteinuria is most likely to
begin. Onset of proteinuria heralds a predictable se-
quence of additional changes (i.e., decreased growth,
diminishing urine concentrating ability, and increas-
ing blood urea nitrogen and serum creatinine values)
during the next few months. Although renal lesions
progress and renal function declines during this pe-
riod, clinical signs of illness are subtle and easily
overlooked, even by attentive owners.
In this study, ECSs with FN lived three-to-nine
months after onset of proteinuria and two-to-seven
months after definitive diagnosis of FN by TEM ex-
amination of renal biopsy specimens. Survival times
would have been longer if the authors had waited
until onset of clinical signs (e.g., reduced appetite,
vomiting) before performing euthanasia. Conversely,
survival times might have been shorter if the diets of
affected dogs had not been changed; a similar dietary
modification prolonged survival times of Samoyeds
with X-linked HN.20
Based on results of this study, ECSs suspected to
be at risk for FN should be screened for proteinuria
beginning when they are four-to-five months old. A
renal biopsy should not be performed solely because
a screening test was positive for proteinuria; how-
ever, proteinuria that is substantial and persistent is a
compelling reason to consider further evaluation by
renal biopsy. The authors recommend the use of UP:C
ratios to evaluate the magnitude of proteinuria.
Routine light microscopic evaluation of renal bi-
opsy samples is not sufficient for definitive diagnosis
of FN. A portion of the specimen containing glomer-
uli must be examined by TEM to detect characteristic
GCBM changes. Transmission electron microscopy
of suitably preserved samples can be obtained at sev-
eral centers. Personnel at local medical centers or
colleges of veterinary medicine should be contacted
several days prior to obtaining renal biopsy samples
to obtain proper fixative solutions. The volume of
TEM fixative needed is small and inexpensive and
May/June 1998, Vol. 34 Familial Nephropathy 195

can be obtained from the center accepting samples for 12. Kashtan CE, Michael AF. Perspectives in clinical nephrology: Alport
syndrome. Kidney Int 1996;50:1445–63.
TEM evaluation. Costs involved in obtaining TEM 13. Jansen B, Thorner P, Baumal R, et al. Samoyed hereditary glomerulopathy
are primarily for packaging, shipping, sample pro- (SHG): evolution of splitting of glomerular capillary basement mem-
branes. Am J Path 1986;125:536–45.
cessing, and use of the electron microscope.
14. Thorner P, Jansen B, Baumal R, et al. Samoyed hereditary glomer-
Wedge biopsy of the kidney, which requires ce- ulopathy: immunohistochemical staining of basement membranes of
liotomy, has been recommended to enhance collec- kidney for laminin, collagen type IV, fibronectin, and Goodpasture
antigen, and correlation with electron microscopy of glomerular capil-
tion of representative portions of renal tissue, lary basement membranes. Lab Invest 1987;56:435–43.
especially for diagnosis of renal dysplasia.21 How- 15. Hood JC, Savige J, Hendtlass A, et al. Bull terrier hereditary nephritis:
ever, in the authors’ hands, less invasive percutane- a model for autosomal dominant Alport syndrome. Kidney Int
1995;47:758–65.
ous needle biopsies are satisfactory for reliable 16. Jansen B, Valli VEO, Thorner P, et al. Samoyed hereditary
diagnosis of FN in ECSs. glomerulopathy: serial clinical and laboratory (urine, serum biochemis-
try, and hematology) studies. Can J Vet Res 1987;51:387–93.
17. Hood JC, Robinson WF, Clark WT, et al. Proteinuria as an indicator of
a
Heartgard 30; Merck & Co., Inc., Rahway, NJ early renal disease in bull terriers with hereditary nephritis. J Sm Anim
b Pract 1991;32:241–8.
Dinamap Blood Pressure Monitor 8300; Critikon Corp., Tampa, FL
c 18. Bodenhamer RD, Hunter JF, Luttgen PJ. Brain stem auditory-evoked
ATL Ultramark 4; Advanced Technology Laboratories, Bothell, WA
d responses in the dog. Am J Vet Res 1985;46:1787–92.
DuPont Discrete Clinical Analyzer; Medical Products Division, DuPont
Co., Wilmington, DE 19. Bartges JW, Osborne CA, Polzin DJ. Recurrent sterile struvite
e urocystolithiasis in three related English cocker spaniels. J Am Anim
Kodak Ektachem creatinine (single-slide method), two-point rate test; Hosp Assoc 1992;28:459–69.
Clinical Chemistry Products Division, Eastman Kodak Co., Rochester, NY
f 20. Valli VEO, Baumal R, Thorner P, et al. Dietary modification reduces
Monopty; CR Bard, Inc., Covington, GA splitting of glomerular basement membranes and delays death due to
g renal failure in canine X-linked hereditary nephritis. Lab Invest
EMbed 812 and Araldite 502; Electron Microscopy Sciences, Fort Wash-
ington, PA 1991;65:67–73.
h 21. Picut CA, Lewis RM. Microscopic features of canine renal dysplasia.
Zeiss 10C; Carl Zeiss, Inc., New York, NY
i Vet Path 1987;24:156–63.
Canine k/d; Hill’s Pet Nutrition, Topeka, KS
j
Clare Gregory, Davis, CA, personal communication, 1995
k
Canine s/d; Hill’s Pet Nutrition, Topeka, KS
l
Canine r/d; Hill’s Pet Nutrition, Topeka, KS

Acknowledgments
Supported by a grant from the American Animal Hos-
pital Association Foundation and by donations from
the English Cocker Spaniel Club of America and sev-
eral English Cocker Spaniel Clubs in the United States
and Canada.

References
1. Krook L. The pathology of renal cortical hypoplasia in the dog.
Nordisk Veterinärmedicin 1957;9:161–76.
2. Persson F, Persson S, Asheim A. Renal cortical hypoplasia in dogs: a
clinical study on uraemia and secondary hyperparathyroidism.
Acta Vet Scand 1961;2:68–84.
3. Freudiger U. Die kongenitale nierenrindenhypoplasie beim bunten cocker-
spaniel. Schweizer Arch Tierheilk 1965;107:547–66.
4. Steward AP, Macdougall DF. Familial nephropathy in the cocker span-
iel. J Sm Anim Pract 1984;25:15–24.
5. Robinson WF, Huxtable CR, Gooding JP. Familial nephropathy in
cocker spaniels. Aust Vet J 1985;62:109–12.
6. Macdougall DF, Nash AS, Cattanach BM. Control scheme for familial
nephropathy in cocker spaniels (letter). Vet Rec 1987;121:134.
7. Koeman JP, Ezilius JW, Biewenga WJ, et al. Zur familiaren nephropathie
der cockerspaniel. Dtsch Tierarzti Wschr 1989;96:174–9.
8. Nash AS. Familial renal disease in dogs. J Sm Anim Pract 1989;
30:178–83.
9. Kelly DF. Renal dysplasia in the dog. In: Grunsell CSG, Hill FWG, eds.
Veterinary annual. 13th ed. Bristol: John Wright, 1972:141–7.
10. Lees GE, Wilson PD, Helman GH, et al. Glomerular ultrastructural
findings similar to hereditary nephritis in 4 English cocker spaniels.
J Vet Int Med 1997;11:80–5.
11. Adler SG, Cohen AH, Glassock RJ. Secondary glomerular diseases. In:
Brenner BM, ed. The kidney. 5th ed. Philadelphia:WB Saunders,
1996:1498–596.
Financial and Productivity Pulsepoints
4C Ad
New

p. 196
 Essential Thrombocythemia in a Dog:
Case Report and Literature Review
A 10.5-year-old, castrated male shih tzu was presented for evaluation of weakness,
pica, and pallor of the mucous membranes. A hemogram indicated an inflammatory
leukogram and a regenerative anemia with spherocytosis and thrombocytosis. The
dog responded well to conservative therapy for immune-mediated hemolytic anemia
(IMHA). However, the thrombocytosis did not resolve. Serial hemograms were
characterized by persistent thrombocytosis (platelet count, 577,000 to 1,200,000/µl)
with abnormal platelet morphology. A systematic investigation ruled out causes of
physiological and reactive thrombocytoses. A diagnosis of essential
thrombocythemia was made by fulfilling the criteria of the Polycythemia Vera Study
Group of the National Cancer Institute. The marked thrombocytosis was
nonresponsive to hydroxyurea therapy. The dog remains healthy despite the marked
increase in the number of circulating platelets. A review of causes of thrombocytoses
in humans and animals is presented, and the criteria for diagnosis of essential
thrombocythemia are examined. J Am Anim Hosp Assoc 1998;34:197–203.

Mili C. Bass, DVM Introduction

A. Eric Schultze, DVM, PhD,
Diplomate ACVP
C cause, a diagnosis of essential thrombocythemia should be pursued.
An increased number of circulating platelets may be a transient find-
ing in an otherwise normal complete blood count (CBC) or may occur
as a secondary complication of various acute or chronic disease pro-
cesses. If thrombocytosis persists with no discernable underlying
Humans with essential thrombocythemia may experience thrombotic
complications related to an increased number of platelets and un-
dergo myelosuppressive therapy to minimize bleeding episodes. There
has been no study in which human patients with essential thrombo-
cythemia simply have been followed without treatment.
Reports of animals with essential thrombocythemia are very rare.
No definitive treatment regimen for essential thrombocythemia has
been established for animals. This report suggests that treatment may
not be warranted in individual cases.

From the Village Veterinary Clinic (Bass),
11249 Kingston Pike,
Farragut, Tennessee 37922 and the
Department of Pathology (Schultze),
College of Veterinary Medicine,
The University of Tennessee,
P.O. Box 1071,
Knoxville, Tennessee 37901-1071.
Address all correspondence and reprint
requests to Dr. A. E. Schultze.
Case Report
A 10.5-year-old, castrated male shih tzu was presented to a private
veterinary hospital for episodic weakness and pica of three weeks’
duration. Pallor of the mucous membranes had been noted by the
owner on the day of presentation. The only abnormality noted on
physical examination was pale, jaundiced mucous membranes. Vacci-
nations for distemper, adenovirus, leptospirosis, parainfluenza,
parvovirus, coronavirus, and rabies were current. Filter and occult
heartworm tests were negative. Fecal samples examined by direct and
flotation methods were negative for parasites. Milbemycin oxime a
(0.5 mg/kg body weight) was administered per os (PO) on a monthly
basis as a heartworm preventative.
The patient had an inflammatory leukogram and a regenerative
anemia with spherocytosis and thrombocytosis [see Table]. A direct
antiglobulin test (Coombs’ test) was strongly positive at 4˚ C and 37˚ C.

JOURNAL of the American Animal Hospital Association 197

198 JOURNAL of the American Animal Hospital Association
Figure 1—Photomicrograph of a blood smear from a dog with
essential thrombocythemia. The arrow points to a platelet with
serpentine shape. A megaplatelet (arrowhead) indicates in-
creased platelet production (Modified Wright’s stains, 100X oil
immersion; bar=4.5 µm).
The only serum biochemical abnormality was an in-
crease in alkaline phosphatase ([ALP], 1,746 IU/L;
reference range, 0 to 400 IU/L). A diagnosis of im-
mune-mediated hemolytic anemia (IMHA) was made,
and treatment was initiated with prednisoneb (1.25
mg/kg body weight, PO q 12 hrs). Amoxicillin-
clavulanic acid c (15.6 mg/kg body weight, PO q 12
hrs) was administered concurrently.
The prednisone dosage was reduced gradually, and
the dog appeared to recover from the hemolytic epi-
sode. A CBC obtained seven weeks after the initial
presentation was considered essentially normal [see
Table], although platelet numbers remained slightly
increased; prednisone administration was stopped.
Abnormalities in the dog’s serum biochemistry pro-
file were consistent with long-term administration of
corticosteroids and included markedly increased ALP
(3,130 IU/L; reference range, 0 to 400 IU/L), in-
creased alanine aminotransferase (ALT) activity (273
IU/L; reference range, 0 to 77 IU/L), and hyperlipi-
demia (serum cholesterol, 520 mg/dl; reference range,
135 to 281 mg/dl; serum triglycerides, 242 mg/dl; ref-
erence range, 7.7 to 53.2 mg/dl). A moderate hyper-
kalemia (serum potassium [K+], 6.46 mmol/L; reference
range, 3.60 to 5.80 mmol/L) also was noted. The
owner was instructed to watch for melena, a renewal
of pica, and to check gum color daily.
One month after cessation of prednisone therapy
(week 11), the dog was presented for hematochezia of
two days’ duration. No other clinical signs had been
observed. Sheather’s sugar solution flotation exami-
nation of the feces was negative for parasitic ova.
Thrombocytosis and a mild, regenerative anemia were
detected by CBC [see Table]. An exploratory laparot-
omy for gastrointestinal biopsy was performed. The
May/June 1998, Vol. 34
liver was pale and reticulated, and the jejunal walls
were thickened. Histopathological analysis of biopsy
specimens indicated a vacuolar hepatopathy consis-
tent with corticosteroid administration and an ex-
tremely mild, acute, eosinophilic enteritis.
Thrombocytosis (platelet count, 577,000/µl to
1,200,000/µl) with abnormal platelet morphology
[Figure 1] persisted in weekly CBCs. A bone-marrow
aspirate biopsy showed myeloid hyperplasia, mild
erythroid hypoplasia, and adequate iron stores. Mega-
karyocytic cells appeared adequate in number and a
differential count indicated 8% Stage I (i.e., mega-
karyoblasts), 17% Stage II (i.e., promegakaryocytes),
and 75% Stage III (i.e., megakaryocytes). This distri-
bution of megakaryopoietic cells was deemed normal
for the dog.1 Serum iron concentration (138 µg/dl;
reference range, 45 to 210 µg/dl) was within normal
limits. Plasma thrombopoietin (77% normal canine
pooled plasma), measured by the immunothrom-
bocythemic mouse assay, was normal. Direct anti-
globulin tests were repeatedly negative. A low-dose
dexamethasone suppression test indicated a slightly
elevated baseline plasma cortisol level with normal
suppression. Based on these results, a diagnosis was
made of probable essential thrombocythemia.
Treatment was begun with hydroxyurea d (25 mg/
kg body weight, PO q 12 hrs for seven days; mainte-
nance dose, 16.25 mg/kg body weight, PO q 24 hrs).
At initiation of treatment, the patient’s platelet count
was 925,000/µl [see Table]. After three weeks of
maintenance therapy (week 23), the platelet count
had fallen only to 747,000/µl, with the rest of the
CBC remaining essentially stable [see Table]. At this
time, the hydroxyurea maintenance dosage was in-
creased to 16.25 mg/kg body weight, PO every 12
hours. Complete blood counts were repeated at weekly
intervals. The patient’s thrombocytosis was only par-
tially responsive to hydroxyurea, with platelet counts
ranging from 639,000/µl to 1,015,000/µl [see Table].
In contrast, the erythron was very sensitive to hy-
droxyurea treatment. A potentially life-threatening
anemia developed after 2.5 months (week 27) of therapy
[see Table], and hydroxyurea therapy was stopped.
Supplementation with irone (5 ml, PO q 12 hrs) and
vitamin B-12f (1 ml administered subcutaneously once a
week) was initiated as a potential stimulus to the eryth-
ron. A thyroid profile was characterized by low serum
concentrations of triiodothyronine (T3) and thyroxine
(T 4), as well as free T3 and T 4, but normal serum thyroid
stimulating hormone concentrations were present. An
additional low serum concentration of total T4 was found
upon review of the patient’s medical records from years
past, and thyroid replacement was started on a trial
basis. The anemia resolved gradually over four weeks
(week 31); however, the thrombocytosis continued
[see Table]. Biweekly CBCs have remained stable,
May/June 1998, Vol. 34
Appendix 1
Causes of Physiological and Reactive
Thrombocytosis in Humans and Animals
Cushing’s disease
Drug therapy: glucocorticoids, epinephrine, vincristine
Exercise
Fractures
Hepatic cirrhosis/hepatopathy
Hemorrhage, acute
Immune-mediated disease
Infections, acute or chronic
Inflammatory conditions, acute or chronic
Iron deficiency
Low infant birth weight
Malignancies
Osteoporosis
Rebound from thrombocytopenia
Splenectomy; asplenic or hyposplenic state
Surgery
Trauma
with a persistent thrombocythemia [see Table]. The
patient remains clinically normal.
Discussion
Essential thrombocythemia is a rare myeloprolifera-
tive disorder, characterized by a sustained increase in
the number of circulating platelets.1,2 The term essen-
tial thrombocythemia is synonymous with idiopathic
thrombocythemia, primary thrombocythemia, primary
hemorrhagic thrombocythemia, primary thrombohem-
orrhagic thrombocythemia, thromboblasthemia, and
piastrinemia. 3 Humans with essential thrombocy-
themia are predisposed to recurrent hemorrhage (par-
ticularly gastrointestinal bleeding) and to thrombosis,
due to thrombocytosis. 3 Thrombocytosis in dogs and
cats has been defined as platelet counts greater than
500x10 9 platelets/L4 or greater than 600x10 9 plate-
lets/L. 5 Essential thrombocythemia may be character-
ized by a pseudohyperkalemia, presumably due to a
portion of the measured serum K + concentration being
released from platelets during the clotting process. 1,5
The shih tzu had a normal serum K+ concentration
upon initial presentation when IMHA was diagnosed.
The serum K + was elevated later in the course of his
illness. Reimann, et al.5 found that serum K + concen-
trations were significantly higher than plasma K+
concentrations in normal dogs and in dogs with throm-
bocytosis, with no differences in serum-plasma con-
centrations of sodium or chloride.
A diagnosis of essential thrombocythemia is estab-
lished by eliminating other causes of thrombocytosis,
Essential Thrombocythemia 199
which can be either physiological, reactive, or myelo-
proliferative in origin. Physiological thrombocytosis
is transient and occurs with excitement or exercise,
due to splenic contraction or increased blood flow.
Reactive thrombocytosis also is a transient phenom-
enon, which may accompany chronic inflammatory
disorders, especially those involving the intestines,
kidneys, or joints. Reactive thrombocytosis is associ-
ated with various clinical diseases, including iron
deficiency (usually from chronic blood loss), endo-
crine disorders (especially hyperadrenocorticism),
acute infections, hemorrhage or trauma, surgery, certain
solid tumors, and antineoplastic agents [Appendix
1]. 4,7 Essential thrombocythemia is a myeloprolifera-
tive disease which must be differentiated from
megakaryoblastic leukemia, 2 the latter of which is
characterized by massive proliferation of megakaryo-
cytes in bone marrow, infiltration of megakaryocytes
into other tissues, and a variable number of circulat-
ing platelets and megakaryoblasts. 2,7,8 These two dis-
orders may be the same disease process seen at
different stages of progression.2
In humans, essential thrombocythemia is consid-
ered a clonal disorder involving a multipotent stem
cell, 9 and as such may be a preneoplastic condition
with risk of leukemic transformation. A report by
Degen, et al. suggests such an evolution from essen-
tial thrombocythemia to chronic myelogenous leuke-
mia over an 18-month period in a standard poodle. 10
In homeostasis, megakaryocytopoiesis is depen-
dent upon a balance between circulating platelet mass
and production of thrombopoietin (i.e., thrombocyto-
sis-stimulating factor).1 Thrombocytopenia would be
expected to cause compensatory thrombopoietin pro-
duction. In conditions that cause physiological or reac-
tive thrombocytosis, thrombopoietin should decrease.
In essential thrombocythemia, thrombocytosis may
occur in the face of normal thrombopoietin activity.
Approximately 30% of humans diagnosed with es-
sential thrombocythemia are clinically asymptomatic
when thrombocytosis is detected on routine blood
testing.3 Symptomatic human patients present with
venous or arterial thromboses or both, bleeding, or
anemia. Veterinary reports of essential thrombo-
cythemia are very rare. Lethargy and weight loss were
the common presenting complaints in three previ-
ously reported canine cases 6,10–12 as well as in one
feline case report of essential thrombocythemia. 13
Varying degrees of anemia were seen in the veteri-
nary patients, either upon presentation or shortly
thereafter. Pica was reported in the history of the cat,
along with polyphagia and intermittent vomiting.
Strict criteria for the diagnosis of essential throm-
bocythemia in humans were established in 1986 by
the Polycythemia Vera Study Group of the National
Cancer Institute [Appendix 2].5,13,14 Criterion I sets
200 JOURNAL of the American Animal Hospital Association May/June 1998, Vol. 34

Table
Hemograms from a Dog with Essential Thrombocythemia

Date
Week 20
Initial (Hydroxyurea
Hematological Findings Presentation Week 7 Week 11 Started) Week 23
†
Total protein (g/dl) 6.8 7.3 ND ND ND
Erythrocyte count ND ND ND 5.22 ND
(x106 /µl)
Hemoglobin (g/dl) 3.9 11.8 10.9 12.3 10.6
Hematocrit (%) 13.4 36.2 32.8 34.8 32.3
Mean corpuscular ND ND ND 66.7 ND
volume (fl)
Mean corpuscular 29 32.6 33.2 35.3 32.8
hemoglobin
concentration (g/dl)
Leukocyte count (/µl) 34,952 14,100 15,600 14,300 10,500
Segmented neutrophils 25,165 11,139 12,792 11,154 7,035
(/µl) (%) (72%) (79%) (82%) (78%) (67%)
Band neutrophils 3,495 282 312 0 105
(/µl) (%) (10%) (2%) (2%) (1%)
Lymphocytes (/µl) (%) 5,243 1,974 780 1,562 2,625
(15%) (14%) (5%) (14%) (25%)
Monocytes (/µl) (%) 699 282 1,404 223 0
(2%) (2%) (9%) (2%)
Eosinophils (/µl) (%) 350 423 312 669 735
(1%) (3%) (2%) (6%) (7%)
Basophils (/µl) (%) 0 0 0 0 0
Platelets (/µl) 752,000 577,000 757,000 925,000 747,000
Comments‡ 1+ sphero; —— 2+ aniso; —— 1+ aniso;
2+ polychro; 2+ poik; 1+ poik;
4+ aniso; few large 1+
few Howell- platelets polychro
Jolly bodies;
5 nRBCs/
100 WBCs
* Duncan JR, Prasse KW, Mahaffey EA. Veterinary laboratory medicine clinical pathology. 3rd ed. Ames: Iowa State Univ Press, 1994:235–8.
†
ND=test not done
‡
Sphero=spherocytes; polychro=polychromasia; aniso=anisocytosis; nRBCs=nucleated red blood cells; WBCs=white blood cells; poik=poikilocytosis
 May/June 1998, Vol. 34 Essential Thrombocythemia 201

Week 25 Week 27 Week 31 Week 65 Week 72 Reference Ranges*

8.2 6.7 7.6 6.9 7.9 6.0–7.5
4.66 ND ND ND 7.22 4.95–7.87

11.2 4.9 12.1 13.7 16.2 11.9–18.9

31.5 15.2 39.4 43.3 45.3 35–57
67.6 ND ND ND 62.7 66–77

35.5 32.2 30.7 31.6 35.8 32–36

11,900 30,500 17,400 18,800 12,500 5,000–14,000

8.806 21,960 14,616 15,040 10,250 2,900–12,000
(74%) (72%) (84%) (80%) (82%)
0 3,050 0 188 125 0–450
(10%) (1%) (1%)
1,428 4,270 1,218 2,256 1,000 400–2,900
(12%) (14%) (7%) (12%) (8%)
595 0 348 564 125 100–1,400
(5%) (2%) (3%) (1%)
1,071 1,220 1,218 752 1,000 0–1,300
(9%) (4%) (7%) (4%) (8%)
0 0 0 0 0 0–140
1,015,000 905,000 960,000 815,000 639,000 211,000–500,000
Few large 2+ aniso; 2 nRBCs/ —— 1 nRBC/ ——
platelets 2+ polychro; 100 WBCs 100 WBCs
19 nRBCs/
100 WBCs

is
202 JOURNAL of the American Animal Hospital Association
Appendix 2
Criteria for the Diagnosis of Essential
Thrombocythemia in Humans
I. Platelet count >600,000/µl
II. Hemoglobin <13 g/dl
III. Stainable iron in bone marrow or failure of iron
trial
IV. No Philadelphia chromosome
V. Absence of collagen fibrosis on bone-marrow
examination
VI. No known cause of reactive thrombocytosis
the lower limit for the platelet count at 600,000/µl,
although much higher counts are noted commonly.
Criteria II and III are utilized to exclude a diagnosis
of polycythemia vera in which thrombocytosis also
can be seen. Criterion IV, absence of Philadelphia
chromosome on karyotypic examination of the mar-
row, excludes chronic myelogenous leukemia and is
used prognostically in humans. Leukemic transfor-
mation appears to be less likely in human patients
with essential thrombocythemia in whom the Phila-
delphia chromosome is not detected. Such chromo-
somal markers have not been documented in domestic
animals. Absence of bone-marrow collagen fibrosis
(Criterion V) excludes those patients having myelofi-
brosis with myeloid metaplasia; a marked thrombo-
cytosis can accompany this condition occasionally.
Criterion VI excludes those patients in whom a condi-
tion (e.g., malignancy, chronic inflammatory disease,
history of splenectomy) is identified as producing
thrombocytosis.
In the shih tzu, the thrombocytosis was persistent
and of extreme magnitude; therefore, physiological
thrombocytosis was eliminated from the differential
diagnosis. The physical examination, results of surgi-
cal biopsies, and bone-marrow cytology including
stainable iron, failure of iron trial to resolve thrombo-
cytosis, normal plasma thrombopoietin, and normal
suppression of plasma cortisol with low-dose dexa-
methasone administration were used to rule out po-
tential causes of reactive thrombocytoses. The
magnitude of thrombocytosis coupled with variation
in platelet morphology [Figure 1] and poor response
to hydroxyurea suggest that essential thrombocythemia
is the more appropriate diagnosis in this case.
Treatment of human patients with essential throm-
bocythemia has included administering hydroxyurea,
busulfan, melphalan, radioactive phosphorus, recom-
binant interferon alpha, or antiplatelet aggregation
agents, and performing plateletpheresis. 1,3,7 Hydroxy-
urea currently is considered to be the most effica-
cious therapy with the least number of deleterious
May/June 1998, Vol. 34
side effects. 3 Simpson, et al. utilized vincristine,
cytosine arabinoside, cyclophosphamide, and pred-
nisolone as combination chemotherapy in an eight-
year-old, female Irish setter with suspected essential
thrombocythemia.12 Unlike the shih tzu, the Irish
setter’s blood smears contained a large number of
blast cells originating from the bone marrow; her
marrow also contained many megakaryocytes with
immature and mature platelets. No necropsy was per-
mitted, so tissue infiltration of megakaryocytes could
not be evaluated. However, it could be argued that
this patient exhibited megakaryoblastic leukemia
rather than essential thrombocythemia. In contrast,
the shih tzu had no circulating blast cells. The bone
marrow contained megakaryocytes normal in num-
ber, appearance, and maturation sequence. Mega-
karyocytes were not seen in surgical biopsies of
several other tissues. A diagnosis of essential throm-
bocythemia was made based upon the criteria of the
Polycythemia Vera Study Group.
The shih tzu is doing well at this time. The current
treatment of thyroid supplementation has controlled
the anemia but has had no effect on the persistent
thrombocythemia. Despite having persistent throm-
bocythemia, which in humans is associated often with
thrombosis and death, this dog appears clinically nor-
mal. More cases of this disease will have to be stud-
ied in dogs before effective treatment regimens can
be developed or indeed before it can be determined
whether or not treatment is required.
Conclusion
Essential thrombocythemia should be included in the
differential diagnoses of dogs with persistently in-
creased platelet counts. A systematic investigation is
necessary to rule out causes of physiological and re-
active thrombocytoses. Diagnosis of essential throm-
bocythemia is dependent upon fulfilling the criteria
of the Polycythemia Vera Study Group of the Na-
tional Cancer Institute. Treatment for animals with
this unusual myeloproliferative disease is controver-
sial, and more cases will need to be studied before
definitive therapeutic recommendations can be made.
a
Interceptor; Ciba, Greensboro, NC
b
Vedco; Danbury, Inc., Danbury, CT
c
Clavamox; SmithKline Beecham, West Chester, PA
d
Professional Compound Centers of America, Inc., Houston, TX
e
LiquiTinic; PRN Pharmaceutical Co., Pensacola, FL
f
Butler Vitamin B Complex; Butler Co., Columbus, OH
Acknowledgments
The authors wish to acknowledge the contribution of
Dr. T. P. McDonald (from the College of Veterinary
Medicine, The University of Tennessee) for perform-
ing the thrombopoietin bioassay.
May/June 1998, Vol. 34 Essential Thrombocythemia 203

References 8. Shull RM, DeNovo RC, McCracken MD. Megakaryoblastic leukemia in

a dog. Vet Path 1986;23:533–6.
1. Jain NC. Essentials of veterinary hematology. Philadelphia: Lea &
9. Fialkow PJ, Faguet GB, Jacobson RJ, Vaidya K, Murphy S. Evidence
Febiger, 1993:123–5, 431–45.
that essential thrombocythemia is a clonal disorder with origin in a
2. Reagan WJ, Rebar AH. Platelet disorders. In: Ettinger SJ, Feldman EC, multipotent stem cell. Blood 1981;58:916–9.
eds. Textbook of veterinary internal medicine. 4th ed. Vol 2. Philadel-
10. Degen MA, Feldman BF, Turrel JM, Goding B, Kitchell B, Mandell CP.
phia: WB Saunders, 1995:1964–76.
Thrombocytosis associated with a myeloproliferative disorder in a dog.
3. Mughal TI. Primary thrombocythemia: a current perspective. Stem Cells J Am Vet Med Assoc 1989;194:1457–9.
1995;13:355–9.
11. Tablin F, Jain NC, Mandell CP, Hopper PE, Zinkl JG. Ultrastructural
4. Hammer AS. Thrombocytosis in dogs and cats: a retrospective study. analysis of platelets and megakaryocytes from a dog with probable
Comp Haematol Int 1991;1:181–6. essential thrombocythemia. Vet Path 1989;26:289–93.
5. Reimann KA, Knowlen GG, Tvedten HW. Factitious hyperkalemia in 12. Simpson JW, Elsa RW, Honeyman P. Successful treatment of suspected
dogs with thrombocytosis. The effect of platelets on serum potassium essential thrombocythaemia in the dog. J Sm Anim Pract 1990;
concentration. J Vet Int Med 1989;3:47–52. 31:345–8.
6. Hopper PE, Mandell CP, Turrel JM, Jain NC, Tablin F, Zinkl JG. 13. Hammer AS, Couto CG, Getzy D, Bailey MQ. Essential thrombocythemia
Probable essential thrombocythemia in a dog. J Vet Int Med 1989; in a cat. J Vet Int Med 1990;4:87–91.
3:79–85.
14. Murphy S, Iland H, Rosenthal D, Laszlo J. Essential thrombocythemia:
7. Williams WJ. Thrombocytosis. In: Williams WJ, Beutler E, Erslev AJ, an interim report from the Polycythemia Vera Study Group. Semin
Lichtman MA, eds. Hematology. 4th ed. New York: McGraw-Hill, Hematol 1986;23:177–82.
1990:1403–6.

Summit Hills
B&W 1/4 Page Ad
New
 Diabetes Mellitus, Hyperadrenocorticism,
and Hypothyroidism in a Dog
An unusual combination of three endocrinopathies found in one dog is described. A
six-year-old, spayed female, mixed-breed dog presented with polyuria, polydipsia,
polyphagia, and weight loss. She was diagnosed with diabetes mellitus but was
suspected of having insulin resistance and was diagnosed subsequently with
hyperadrenocorticism. Persistent hypercholesterolemia led to the suspicion and
eventual diagnosis of hypothyroidism. The dog has responded well to medical
therapy, and her clinical signs and biochemical changes have resolved. A literature
search did not identify a similar-reported polyendocrinopathy.
J Am Anim Hosp Assoc 1998;34:204–7.

Rebecka S. Hess, DVM Case Report

Cynthia R. Ward, VMD, PhD
C weight loss. The dog had no previous medical conditions or proce-
From the Department of Clinical Studies,
School of Veterinary Medicine,
University of Pennsylvania,
Philadelphia, Pennsylvania 19104-6010.
A six-year-old, spayed female, mixed-breed dog presented to the
Veterinary Hospital of the University of Pennsylvania with a one-
month history of polyuria, polydipsia (PU/PD), polyphagia, and
dures other than a routine ovariohysterectomy at six months of age,
and she was receiving no medications at the time of presentation. The
dog was underweight (22 kg), well hydrated, and alert. Her rectal
temperature (38.2˚ C), heart rate (108 beats per min), and respiratory
rate (36 breaths per min) were within normal limits, as was the rest of
her physical examination.
A complete blood count (CBC), a chemistry screen, b urinalysis,
urine culture, and fecal parasitological examination were performed.
The CBC was within normal limits. Moderate hyperglycemia (blood
glucose, 389 mg/dl; reference range, 65 to 135 mg/dl) and moderate
hypercholesterolemia (cholesterol, 518 mg/dl; reference range, 150
to 250 mg/dl) were the only significant findings noted on the chemis-
try screen. Glucosuria (+4) was the only abnormality apparent on
urinalysis; the urine specific gravity was 1.030. Parasites were not
detected on fecal examination. A blood glucose measurement (371
mg/dl) was repeated on day one to confirm the hyperglycemia.
Persistent hyperglycemia and glucosuria were diagnostic of diabe-
tes mellitus. The dog was admitted to the hospital for insulin regula-
tion, and blood glucose concentration was measured every two hours
for 60 hours. She was fed half of her daily caloric requirements in the
form of a high-fiber, complex carbohydrate dietc and was given neu-
tral protamine Hagedorn (NPH) insulin (0.5 U/kg body weight, sub-
cutaneously [SC]). The dog remained hyperglycemic (blood glucose,
371 to 416 mg/dl over 12 hrs), and the dose of insulin was increased
(first to 0.68 U/kg body weight, SC and then 12 hours later to 0.86 U/kg
body weight, SC bid), which appeared to provide reasonable glyce-
mic control (the blood glucose concentration range was 112 to 358
mg/dl over the next 20 hrs). Prior to discharge, a resting total serum
thyroxine (T4 ) concentration (1.6 µg/dl; reference range, 1.5 to 4 µg/
dl) was evaluated to investigate hypothyroidism as a cause of the
hypercholesterolemia and was found to be low normal. A urinalysis
also was performed; hyposthenuria (urine specific gravity of 1.009)
had become apparent, and the glucosuria had resolved.

204 JOURNAL of the American Animal Hospital Association

May/June 1998, Vol. 34
The dog was discharged and was to be fed half of
its caloric requirements in the form of a high-fiber,
complex carbohydrate diet c twice a day and receive
NPH insulin (0.86 U/kg body weight, SC bid) after
each meal. She was sent home with praziquantel (6.2
mg/kg body weight, per os [PO] to be given once) and
febantel (8.7 mg/kg body weight, PO sid for three
consecutive days) in case parasites were missed on
fecal examination. The urine culture yielded no aero-
bic growth. By day 83, the clinical signs had re-
solved, and the body weight had increased to 25 kg.
The dose of insulin had been increased gradually to
1.52 U/kg body weight, SC twice a day based on
interim blood glucose curves, twice-daily urine glu-
cose measurements, and owner observations. The dog
was admitted for a glucose curve (day 83), and insu-
lin resistance was suspected because the dog was
hyperglycemic (the blood glucose concentration range
was 217 to 382 mg/dl over a period of 24 hrs) on a
dose of insulin greater than 1.50 U/kg body weight,
SC twice a day. Storage, handling, and administration
of insulin were reviewed with the owner and were
found to be adequate.
A CBC, chemistry screen, urinalysis, urine cul-
ture, abdominal ultrasonography, and thoracic
radiography were performed (day 84) to rule out un-
derlying disease which may cause insulin resistance.
The abnormalities found were hyperglycemia (blood
glucose, 361 mg/dl), hypercholesterolemia (cholesterol,
386 mg/dl), glucosuria (+3), and a mildly enlarged,
hyperechoic liver. Persistent hyperglycemia and glu-
cosuria indicated that the diabetes mellitus was not
regulated adequately. Concurrent hyperadrenocorti-
cism causing insulin resistance was suspected. A low-
dose dexamethasone suppression (LDDS) test was
performed to assess adrenal gland function (day 85).
The resting cortisol concentration was 4.6 mg/dl (ref-
erence range, 0.5 to 5.0 mg/dl); the four-hour cortisol
concentration was less than 0.5 mg/dl; and the eight-
hour cortisol concentration was 1.9 mg/dl (reference
range, less than 1 mg/dl). The LDDS test was diag-
nostic of pituitary-dependent hyperadrenocorticism
(PDH), because the four-hour cortisol concentration
suppressed to below 0.5 mg/dl and the eight-hour
cortisol concentration escaped to above 1.4 mg/dl.
On day 87, mitotane (o,p’-DDD) induction (25 mg/kg
body weight, PO sid for seven days) began. An
adrenocorticotropic hormone d (ACTH) stimulation
test performed on day 94 showed insufficient induc-
tion because both the pre- and poststimulation values
(3.0 and 4.2 mg/dl, respectively; normal values for a
dog adequately treated with o,p’-DDD are 1 to 2.5
mg/dl) were above 2.5 mg/dl. Mitotane induction was
continued at 25 mg/kg body weight, PO once daily
for five more days. On day 101, the results of the
ACTH stimulation test indicated that the dog was
Polyendocrinopathy 205
induced properly (pre- and poststimulation cortisol
concentrations were 1.7 and 2.2 mg/dl, respectively).
Maintenance o,p’-DDD therapy was started at 25 mg/kg
body weight per week, divided twice a week.
A month later, the dog presented for reevaluation.
She was doing well, and the dose of insulin had been
decreased by the owner (based on urine glucose mea-
surements) and was presently 1.28 U/kg body weight,
SC twice a day (the body weight had increased to 28
kg). A 24-hour glucose curve, urinalysis, ACTH
stimulation test, and liver panel (i.e., blood urea ni-
trogen, alkaline phosphatase, alanine aminotrans-
ferase, total bilirubin, albumin, cholesterol, and
ammonia concentration) were performed (on day 131).
The current dose of insulin appeared to provide good
glycemic control (the blood glucose concentration
range was 104 to 247 mg/dl over 24 hrs). The ACTH
stimulation test and liver panel were performed prior
to feeding the dog, which had been fasted for 10
hours. The pre- and postACTH stimulation cortisol
concentrations were 2.4 and 2.2 mg/dl, respectively,
and indicated that the PDH was regulated well. Fast-
ing hypercholesterolemia (cholesterol, 474 mg/dl) was
present in the face of well-regulated diabetes mellitus
and PDH.
A resting total serum T 4 concentration (1.0 µg/dl;
reference range, 1.5 to 4.0 µg/dl) on day 133 was low
and suggestive of hypothyroidism. A thyroid-stimu-
lating hormone e (TSH) stimulation test was
performed (on day 134) and was diagnostic of
hypothyroidism with a low-resting total serum T 4 con-
centration (1.0 µg/dl) and a low six-hour poststimula-
tion total serum T4 concentration (1.8 µg/dl; normal
should increase by 2 µg/dl or by twofold over the
resting concentration). Levothyroxine supplementa-
tion (0.018 mg/kg body weight, PO bid) was initiated
(on day 136). The dose of insulin was decreased to
1.14 U/kg body weight, SC twice a day based on the
glucose curve and because less insulin resistance was
anticipated with treated hypothyroidism. The dose of
o,p’-DDD was not changed.
The dog presented three months later for reevalua-
tion. Clinical signs had resolved, and her physical
examination was normal. She weighed 27.6 kg. The
doses of insulin, o,p’-DDD, and levothyroxine were
unchanged. A cholesterol concentration measurement,
urinalysis, 24-hour glucose curve, ACTH stimulation
test, and resting total serum T 4 concentration six hours
after levothyroxine administration were performed (on
day 226) to evaluate the three endocrinopathies. The
hypercholesterolemia had resolved (cholesterol, 174
mg/dl), and the diabetes mellitus, PDH, and hypothy-
roidism appeared well controlled based on clinical
signs and endocrine testing (the blood glucose con-
centration range was 148 to 278 mg/dl over 24 hrs;
pre- and postACTH stimulation cortisol concentra-
206 JOURNAL of the American Animal Hospital Association
tions were 1.3 and 2.1 mg/dl, respectively; and the T4
concentration was 3.3 µg/dl). The dog has been seen
every three-to-six months for reevaluation of her en-
docrinopathies, and she continues to do well 2.5 years
later.
Discussion
Although the initial clinical signs and biochemical
changes may have been due to diabetes mellitus alone,
it is very possible that hyperadrenocorticism was
present since the onset of clinical signs, contributing
to some of these changes. Polyuria, polydipsia,
polyphagia, and hypercholesterolemia are seen in both
diabetes mellitus and hyperadrenocorticism.1–3 Weight
loss, which also was part of the presenting complaint,
is usually not characteristic of hyperadrenocorticism.2
In dogs with concurrent diabetes mellitus and hyper-
adrenocorticism, it is recommended to treat the
diabetes mellitus first and diagnose the hyperadreno-
corticism once some glycemic control is achieved
with insulin.4 The reason for this recommendation is
that diabetes mellitus and hyperadrenocorticism share
similar clinical signs and biochemical changes,5 and
treatment of diabetes mellitus may resolve the changes
suggestive of hyperadrenocorticism. Additionally, ad-
renal gland function testing may be difficult to inter-
pret in dogs with unregulated diabetes mellitus or
other nonadrenal disease,6 although test results are
reliable in diabetic patients properly controlled with
insulin.7 When the LDDS test was performed, blood
glucose concentration was measured every two hours
to ensure the dog was not hypoglycemic during the
test. Hypoglycemia could result in compensatory se-
cretion of glucocorticoids that would cause a false-
positive LDDS test result.
The dog presented with concomitant polyphagia
and weight loss which may be seen with diabetes
mellitus, gastrointestinal parasitism, malassimilation
disorders (e.g., exocrine pancreatic insufficiency), and
protein-losing nephropathy. The dog was treated for
gastrointestinal parasitism (even though such para-
sites were not detected on fecal examination) to ex-
clude this possible cause of weight loss. No additional
clinical signs or biochemical changes were sugges-
tive of intestinal malassimilation, and a protein-
losing nephropathy was not likely in the absence of
proteinuria. A high-fiber, complex carbohydrate diet
was chosen even though it provides reduced caloric
intake, because it may improve glycemic control and
eventually promote weight gain.8
Hypercholesterolemia was noted at the onset of
clinical signs, and likely etiologies (e.g., diabetes melli-
tus, hyperadrenocorticism, hypothyroidism) were con-
sidered.3 The hyperlipidemia seen in diabetes mellitus
may be the result of insulin deficiency, 3 decreased
lipoprotein lipase activity,3 and altered hepatic func-
May/June 1998, Vol. 34
tion. 9 Hyperlipidemia associated with hyperadreno-
corticism may be due to the effect of glucocorticoids
on lipid metabolism,10 glucocorticoid-induced insu-
lin resistance, 9 and down regulation of hepatic low-
density lipoprotein receptors. 9 In hypothyroidism, the
hyperlipidemia is thought to be due to decreased he-
patic low-density lipoprotein receptors and decreased
lipoprotein lipase activity. 9 The initial total serum T 4
concentration was low normal, but since nonthyroidal
illness (e.g., diabetes mellitus) can lower total serum
T 4 concentration 11 and since diabetes mellitus can in
itself cause hypercholesterolemia, 3,9 it was decided to
treat the diabetes mellitus first. Other diagnostics for
hypothyroidism would be pursued only if hypercho-
lesterolemia persisted with regulated diabetes mellitus.
Once hyperadrenocorticism was diagnosed, the investi-
gation of possible etiologies for the hypercholesterolemia
was postponed further, because hyperadrenocorticism
also is associated with hypercholesterolemia.3 Addition-
ally, because glucocorticoids suppress TSH secretion,12
the hyperadrenocorticism was treated before repeating a
resting total serum T4 measurement.
Urine cultures were performed twice because a
patient with either diabetes mellitus or hyperadreno-
corticism is immunocompromised and is at increased
risk of developing a urinary tract infection (UTI),
which is a common cause of insulin resistance. 13 An
infection may be difficult to diagnose based on a
urine sediment alone, because diabetes mellitus and
hyperadrenocorticism cause immunosuppression. In
the absence of a proper immune response, fewer white
blood cells than expected may be seen in the urine
sediment, even when a UTI is present.
The dose of insulin purposefully was decreased to
allow mild hyperglycemia during the induction phase
with o,p’-DDD and the initial treatment with levo-
thyroxine. Both hyperadrenocorticism and hypothy-
roidism cause insulin resistance, and therefore a
decrease in insulin requirements was anticipated with
treatment. Glucocorticoids cause insulin resistance
by several mechanisms of action, including increased
gluconeogenesis and glycogenesis and decreased pe-
ripheral glucose uptake. 14 Treatment with o,p’-DDD
decreases the concentration of glucocorticoids,
thereby increasing insulin sensitivity. The mechanism
for insulin resistance seen in hypothyroid dogs is not
understood fully; however, such resistance has been
documented and may be reversible with treatment. 15
It is paramount to decrease the dose of insulin prior to
treatment of hyperadrenocorticism or hypothyroid-
ism since a dose of insulin, which is adequate prior to
treatment, may cause detrimental hypoglycemia after
treatment.
The etiologies of the three endocrinopathies docu-
mented in this dog are not known and may be unre-
lated. Immune-mediated disease may be involved in
May/June 1998, Vol. 34
the pathophysiologies of canine diabetes mellitus 16
and hypothyroidism. 17 Pancreatic beta-cell antibodies
were not measured in this dog; it is not known if the
occurrence of such antibodies in dogs with diabetes
mellitus is a cause of pancreatic beta-cell destruction
or a consequence of the disease.18 Antithyroglobulin
antibodies also were not measured, but false-positive
titers have been reported in dogs with nonthyroidal
endocrine disease. 19 Therefore, documentation of such
titers, had they been measured, would not necessarily
indicate that the dog had immune-mediated polyglan-
dular disease. Even if both glands were affected by a
process of immune destruction, it appears as if the
pancreas was affected before the thyroid. When dia-
betes mellitus first was diagnosed, the total serum T4
concentration was low but still within the reference
range, which may occur with concurrent nonthyroidal
disease. 11 Although hyperadrenocorticism was not di-
agnosed yet, it may have been present, and dogs with
hyperadrenocorticism have been shown to have low
T 4 concentrations prior to treatment of the hyper-
adrenocorticism. 20 The fact that the dog did not have
clinical signs characteristically associated with hy-
pothyroidism (e.g., obesity, seborrhea, alopecia,
weakness, lethargy, bradycardia, pyoderma) also sug-
gests that the disease was recognized at an early stage
and was not missed at the time the diabetes mellitus
was diagnosed. Although it is possible that the same
immune process affected the pancreas before the thy-
roid, it also is conceivable that the occurrence of
diabetes mellitus and hypothyroidism is unrelated. If
both the pancreas and the thyroid were affected by an
immune-mediated process, the development of PDH,
which is a hyperplastic or neoplastic disorder of the
pituitary, probably is unrelated to the two other endo-
crinopathies. However, concurrent hyperadrenocorti-
cism and diabetes mellitus commonly are found in the
dog and may be due to glucocorticoid-induced insulin
resistance. 5 In this case, the diabetes mellitus and
hyperadrenocorticism may be related and the occur-
rence of hypothyroidism could be incidental. Polyen-
docrinopathies have a genetic component in humans 21
and may be influenced genetically in dogs. 22 Unfortu-
nately, information on this patient’s litter mates is not
available.
This case demonstrates the stepwise fashion of
diagnosing and managing concurrent endocrinopa-
thies, which share many clinical signs and also are
intertwined metabolically in their effects on lipid and
carbohydrate metabolism.
a
Hematology analyzer; Roche Minos Vet, Burlington, NC
b
Chemistry analyzer; Kodak Ektachem 700, Rochester, NY
c
Canine w/d; Hill’s Pet Nutrition, Topeka, KS
d
H.P. Acthargel; Rhone-Poulenc Rorer, Collegeville, PA
e
Thytropar; Armour, Blue Bell, PA
Polyendocrinopathy 207
References
1. Marmor M, Willeberg P, Glickman LT, Priester WA, Cypess RH,
Hurvitz AI. Epizootiologic patterns of diabetes mellitus in dogs. Am J
Vet Res 1982;43(3):465–70.
2. Ling GV, Stabenfeldt GH, Comer KM, Gribble DH, Schechter RD.
Canine hyperadrenocorticism: pretreatment clinical and laboratory evalu-
ation of 117 cases. J Am Vet Med Assoc 1979;174(11):1211–4.
3. Whitney MS. Evaluation of hyperlipidemias in dogs and cats. Sem Vet
Med Surg (Sm Anim) 1992;7(4):292–300.
4. Hess RS, Ward CR. Diagnosis and treatment of concurrent hyperadreno-
corticism and diabetes mellitus in dogs. Submitted to the Comp Cont Vet
Pract Vet, 1997.
5. Peterson ME, Nesbitt GH, Schaer M. Diagnosis and management of
concurrent diabetes mellitus and hyperadrenocorticism in thirty dogs. J
Am Vet Med Assoc 1981;178(1):66–9.
6. Kaplan AJ, Peterson ME, Kemppainen RJ. Effects of disease on the
results of diagnostic tests for use in detecting hyperadrenocorticism in
dogs. J Am Vet Med Assoc 1995;207(4):445–51.
7. Zerbe CA, Refsal KR, Schall WD, Nachreiner RF, Gossain VV. Adrenal
function in 15 dogs with insulin-dependent diabetes mellitus. J Am Vet
Med Assoc 1988;193(4):454–6.
8. Graham PA, Maskell IE, Nash AS. Canned high fiber diet and postpran-
dial glycemia in dogs with naturally occurring diabetes mellitus. J Nutr
1994;124:2712S–5S.
9. Barrie J, Watson TDG, Stear MJ, Nash AS. Plasma cholesterol and
lipoprotein concentrations in the dog: the effects of age, breed, gender
and endocrine disease. J Sm Anim Pract 1993;34:507–12.
10. Ganong WF. Endocrine functions of the pancreas and the regulation of
carbohydrate metabolism. In: Ganong WF, ed. Review of medical physi-
ology. Norwalk, CT: Appleton & Lange, 1995:306–26.
11. Elliott DA, King LG, Zerbe CA. Thyroid hormone concentrations in
critically ill canine intensive care patients. J Vet Emerg Crit Care
1995;5(1):17–23.
12. Ganong WF. The thyroid gland. In: Ganong WF, ed. Review of medical
physiology. Norwalk, CT: Appleton & Lange, 1995:290–305.
13. Peterson ME. Diagnosis and management of insulin resistance in dogs
and cats with diabetes mellitus. Vet Clin N Am Sm Anim Pract
1995;25(3):691–713.
14. Ganong WF. The adrenal medulla and adrenal cortex. In: Ganong WF,
ed. Review of medical physiology. Norwalk, CT: Appleton & Lange,
1995:327–51.
15. Ford SL, Nelson RW, Feldman EC, Niwa D. Insulin resistance in three
dogs with hypothyroidism and diabetes mellitus. J Am Vet Med Assoc
1993;202(9):1478–80.
16. Elie M, Hoenig M. Canine immune-mediated diabetes mellitus: a case
report. J Am Anim Hosp Assoc 1995;31:295–9.
17. Greco DS, Harpold LM. Immunity and the endocrine system. Vet Clin N
Am Sm Anim Pract 1994;24(4):765–82.
18. Hoenig M, Dawe DL. A qualitative assay for beta cell antibodies.
Preliminary results in dogs with diabetes mellitus. Vet Immunol
Immunopathol 1992;32:195–203.
19. Haines DM, Lording PM, Penhale WJ. Survey of thyroglobulin autoan-
tibodies in dogs. Am J Vet Res 1984;45:1493–7.
20. Peterson ME, Ferguson DC, Kintzer PP, Drucker WD. Effects of spon-
taneous hyperadrenocorticism on serum thyroid hormone concentra-
tions in the dog. Am J Vet Res 1984;45:2034–8.
21. Eisenbarth GS, Jackson RA. The immunoendocrinopathy syndromes. In:
Wilson JD, Foster DW, eds. Williams’ textbook of endocrinology.
Philadelphia: WB Saunders, 1992:1555–66.
22. Eigenmann JE, van der Haage MH, Rijnberk A. Polyendocrinopathy in
two canine littermates: simultaneous occurrence of carbohydrate intol-
erance and hypothyroidism. J Am Anim Hosp Assoc 1984;20:143–8.
 Right-Sided Heart Failure in a Dog with
Primary Cardiac Rhabdomyosarcoma
A seven-year-old, female German shepherd mixed-breed dog was presented with
weakness, inappetence, and a distended abdomen. Right-sided heart failure with
pleural, pericardial, and abdominal effusions; dyspnea; and tachycardia were
identified. The radiographic and electrocardiographic examinations did not allow a
conclusive diagnosis. Echocardiographic findings included a mass in the wall of both
the right atrium and right ventricle, partially occupying the right heart cavities. A
diagnosis of cardiac tumor was made, and the owner elected euthanasia. The
necropsy confirmed a tumor mass located in the right atrium and right ventricle.
A definitive diagnosis of primary cardiac rhabdomyosarcoma was based on
histopathological and immunohistochemical analyses.
J Am Anim Hosp Assoc 1998;34:208–11.

José Pérez, PhD Introduction

Alfredo Pérez-Rivero, PhD Primary cardiac neoplasms are uncommon in domestic animals. Most
have been classified as rhabdomyomas, which are particularly com-
Alberto Montoya, PhD mon in pigs but also have been described in cows, sheep, and dogs.
Rhabdomyomas also have been reported in humans. 1–3 Metastatic
M. Paz Martín, DVM neoplasms to the heart (e.g., hemangiosarcomas, fibromas, fibrosar-
Elena Mozos, PhD comas, lymphomas) as well as heart-based tumors (e.g., chemodecto-
mas) are more common than cardiac muscular tumors. 2,4,5
Rhabdomyosarcomas are uncommon tumors in the dog that mainly
involve the urinary bladder. 3 To the authors’ knowledge, only three,
C primary, canine cardiac rhabdomyosarcomas have been reported. 1,6,7
The purposes of the present paper are to describe the clinical signs
and the electrocardiographic and echocardiographic features of a dog
suffering from cardiac rhabdomyosarcoma, and to report the histo-
pathological and immunohistochemical characteristics of the tumor.
The differential diagnosis is discussed.

From the Departamento de Anatomía
y Anatomía Patológica
Comparadas (Pérez, Martín, Mozos),
Universidad de Córdoba and the
Hospital Veterinario (Pérez-Rivero),
Taco, Tenerife and the
Departamento de Patología Animal
(Montoya),
Universidad de las Palmas de Gran
Canaria, Spain.
Doctor José Pérez’s current address is
the Departamento de Anatomía y
Anatomía Patológica Comparadas,
Facultad de Veterinaria,
Avenida Medina Azahara 9,
14005 Córdoba, Spain.
Case Report
A seven-year-old, female, German shepherd mixed-breed dog was
examined because of inappetence of three days’ duration. There was
no history of vomiting or diarrhea. Weakness and a distended abdo-
men also had been noted for two weeks. On physical examination,
severe ascites, dyspnea, tachycardia (heart rate, 180 beats per min),
weak pulses, and pale, slightly icteric, external mucous membranes
were found. Rectal temperature (39˚ C) was normal. Upon thoracic
auscultation, the intensity of the cardiac sounds was decreased, and
the first one was changing. No murmur was detected. The radio-
graphic examination demonstrated moderate pleural and abdominal
effusions and moderate hypertrophy of the right ventricle [Figure 1].
The hematocrit (40%; reference range, 37.0% to 55.0%) was in the
lower reference range. The biochemical analysis showed a moderate
hypoproteinemia (4.3 g/dl; reference range, 5.3 to 7.7 g/dl) and hy-
poalbuminemia (2.2 g/dl; reference range, 2.2 to 3.1 g/dl); other
parameters (i.e., glucose, urea, creatinine, cholesterol, calcium, ala-
nine aminotransferase, and alkaline phosphatase) were within refer-

208 JOURNAL of the American Animal Hospital Association

May/June 1998, Vol. 34
Figure 1—Ventrodorsal thoracic radiographs of a dog pre-
sented for weakness, inappetance, and a distended abdomen.
Pleural (small arrowhead) and abdominal (large arrowhead)
effusions are evident. The two arrows indicate where the mass
was seen on echocardiography.
Figure 2—Electrocardiogram showing tachycardia (rate, 180
beats per min). Isolated atrial premature complexes, large T
waves, low-voltage QRS complexes, and notches in descend-
ing R waves are shown (25 mm/s; 10 mm/mV).
ence ranges. The laboratory examination of the
abdominal fluid confirmed that it was a modified
transudate (protein, 3.4 g/dl; density, 1.030). The elec-
trocardiogram was characterized by a tachycardia
(rate, 180 beats per min) with isolated atrial prema-
ture complexes, large positive T waves, low-voltage
Cardiac Rhabdomyosarcoma 209
Figure 3—Two-dimensional (2-D) echocardiography. A 3.4 by
2.4-cm mass (arrows ) is seen on the wall of the right atrium and
right ventricle partially occluding both cavities.
QRS complexes, and notched descending R waves
[Figure 2].
The echocardiographic examination demonstrated
a moderate pericardial effusion and a 3.4 by 2.4-cm
diameter mass located in the wall of both the right
atrium and right ventricle [Figure 3]. This mass also
involved the tricuspid valve, partially occluded both
the atrial and ventricular cavities, and moved with the
heart beats. Moreover, a moderate pleural effusion
was found. The abdominal ultrasonogram confirmed
the ascites and showed severe venous congestion in
the liver. A diagnosis of cardiac tumor was made, and
a transcutaneous biopsy was recommended for de-
finitive diagnosis. However, the owner elected eutha-
nasia due to the serious prognosis and bad condition
of the dog.
The main gross lesions found at necropsy were
located in the heart. A 3.4 by 2.4-cm diameter mass
infiltrated the wall of the right atrium and ventricle
and the tricuspid valve. The mass protruded and par-
tially occupied the cavities of the right atrium and
right ventricle. Moderate hypertrophy of the right
ventricle was observed. The tumor mass was irregular
in shape, whitish to grayish, and multifocal petechial
hemorrhages were present. A clear transudate was
removed from the thoracic (70 ml) and abdominal
(1,500 ml) cavities. Other significant gross lesions
consisted of severe hepatic venous congestion and an
enlarged, hyperemic spleen.
Tissue samples were fixed in buffered saline for-
malin (10%) and embedded in paraffin wax. For the
histopathological study, 3-µm thick tissue sections
were stained with the hematoxylin and eosin (H&E),
periodic acid Schiff (PAS), and phosphotungstic acid-
hematoxylin (PTAH) techniques. Immunohistochemi-
cal stainings were performed using the avidin-
biotin-peroxidase complex (ABC) technique. Primary
antibodies employed and their dilutions were mono-
clonal mouse antimuscle actin (HHF35) a (1:50),
210 JOURNAL of the American Animal Hospital Association
Figures 4A, 4B—(A) Photomicrograph of the tumor mass show-
ing round-to-oval and spindle cells (arrows) with vesiculous
nuclei and eosinophilic cytoplasm, surrounded by a moderate
stroma with some infiltrating neutrophils (arrowhead) (Hema-
toxylin and eosin stain; 400X, bar=100 µm); (B) Immunoreactiv-
ity to the antidesmin monoclonal antibody is restricted to some
fusiform and round tumor cells (arrows) (brown color), whereas
the majority of neoplastic cells are unreactive (Avidin-biotin-
complex method, hematoxylin and eosin counterstain; 800X,
bar=50 µm).
polyclonal rabbit antivimentin b (1:200), mono-
clonal mouse antidesmin b (1:50), and monoclonal
mouse antikeratin (RCK 102) b (1:50). Negative
controls were run by replacing the primary anti-
bodies with nonimmune rabbit or mouse sera. Posi-
tive controls included normal myocardium from
the same dog and squamous epithelium for the
antikeratin antibody.
Histopathology
Histopathological analysis demonstrated a neoplasm
invading the myocardium; it was composed of large,
pleomorphic cells arranged in sheets and irregular
cords. Most of the tumor cells were stellate, ovoid, or
polyhedral, with eccentric, basophilic nuclei and large
nucleoli [Figures 4A, 4B]. Some binucleate tumor
cells also were observed. Mitotic figures often were
seen. The cytoplasm was eosinophilic or vacuolated.
No cross striations were observed in H&E-, PAS-, or
PTAH-stained tissue sections. An abundant myxoid
stroma with scattered neutrophils, few eosinophils,
frequent hemorrhages, and small blood vessels was
observed in some areas. Morphologically, these areas
were similar to primitive mesenchymal tissue. In other
areas, tumor cells were fusiform or strap-like, and
they had large, hyperchromatic nuclei with one or
two evident nucleoli and eosinophilic cytoplasm.
Some of these cells showed cross striation on the
PTAH-stained sections.
Histopathological changes in other organs in-
cluded marked congestion in hepatic sinusoids and
diffuse microvacuolar degeneration of hepatocytes.
Severe hyperemia and scarce hematopoietic foci
were observed in the venous sinus of the red splenic
pulp.
May/June 1998, Vol. 34
Figure 5—Immunoreactivity (brown color) to the antimuscle
actin monoclonal antibody in the cytoplasm of numerous pleo-
morphic tumor cells (Avidin-biotin-complex method, hematoxy-
lin and eosin counterstain; 400X, bar=100 µm).
Immunohistochemistry
All tumor cells, as well as normal cardiac muscle
cells, were strongly immunoreactive to the anti-
vimentin antibody. Both tumor cells and normal car-
diac muscle cells were unreactive to the antikeratin
antibody. Normal cardiac muscle cells and most of
the spindle-shaped tumor cells had strong, cytoplas-
mic immunoreactivity to the antimuscle actin anti-
body [Figure 5]. However, stellate and pleomorphic
tumor cells had variable immunoreactivity to this an-
tibody; some showed an intense, diffuse, cytoplasmic
reaction, whereas in others the positivity was weak or
absent. With the antidesmin monoclonal antibody,
tumor cells of the myxoid areas were negative,
whereas some isolated groups of fusiform neoplastic
cells were strongly immunoreactive [Figure 4B]. The
histopathological and immunohistochemical features
were consistent with a diagnosis of primary cardiac
rhabdomyosarcoma (pleomorphic type).
Discussion
Striated muscle neoplasms are rare in all domestic
species, and about one-third of them have been re-
ported in the heart. 3,4 It has been suggested that rhab-
domyosarcomas located in organs without striated
muscle (e.g., urinary bladder, urethra) arise from em-
bryonic remnants of myotomes. This hypothesis is
supported by the early age of presentation and the
clearly embryonic nature of tumor cells. 3 However,
rhabdomyosarcomas from organs with striated muscle
are reported more often in adult dogs (as in the present
case and in two of the three cardiac rhabdomyosarco-
mas reported to date), 1,6 suggesting a noncongenital
origin.
The clinical signs caused by cardiac tumors are
quite variable, and they depend on the location of the
tumor, intracavitary obstruction, degree of infiltra-
tion, and involvement of aortic or pulmonic valves.1,7,8
May/June 1998, Vol. 34
The main clinical findings (i.e., right-sided heart fail-
ure with pleural, pericardial, and abdominal effusions)
found in the present case were similar to those re-
ported in two cases of canine rhabdomyosarcoma, 1,7
whereas signs of hypoadrenocorticism caused by me-
tastasis to the adrenal gland were found in the other
case.6 The right-sided heart failure results from the
intraluminal tumor obliterating the right heart cham-
bers, 7 whereas the electrocardiographic abnormalities
are secondary to infiltration of the myocardium with
damage of the conduction system. 7
The clinical signs found in this dog on the initial
physical examination were consistent with right-sided
heart failure, and the primary differential diagnosis
included heartworm disease, hepatopathy-nephropa-
thy syndrome, lymphangiectasis, right-sided cardiac
insufficiency, dilated cardiomyopathy, cardiac tam-
ponade, congenital anomalies, and cardiac tumor.
Radiography and two-dimensional (2-D) echocar-
diography often are required to make an antemortem
diagnosis of an intracardiac mass. These techniques
provide information about the size, shape, location,
echo pattern, and motion features, as well as about
the pericardial effusion, myocardial function, and car-
diac wall thickness. 8 In this case, echocardiography
allowed a tentative diagnosis of intracardiac tumor
with an accurate prediction of the size and location of
the mass. However, this method does not allow the
identification of the tumor type. The cytological ex-
amination of pericardial fluid does not appear to be
useful in diagnosing intracardiac tumors in dogs with
pericardial effusion. 1,9 Nonetheless, Gonin-Jmaa, et
al. reported that impression smears of the mass, per-
formed during surgery for a canine rhabdomyosar-
coma, were useful in differentiating neoplastic from
nonneoplastic intracardiac lesions.1
The majority of cardiac striated muscle tumors
reported in domestic animals have been classified as
benign rhabdomyomas because of the low mitotic
index and clear cytoplasmic cross striation.3 How-
ever, in the case described here, the tumor mass was
composed mainly of pleomorphic mono- and binu-
cleated cells with a high mitotic index and surrounded
by an abundant myxoid stroma. Similar histological
features have been described in the other three canine
cardiac rhabdomyosarcomas. 1,6,7 Only one canine car-
diac rhabdomyoma has been described. 4
In the case described herein, poorly differentiated
tumor cells (i.e., stellate, ovoid, and polyhedral) were
uniformly negative for desmin, whereas isolated
groups of fusiform neoplastic cells were positive for
this antigen. The distribution pattern of desmin im-
munoreactivity reflects the different stages of muscle
differentiation of tumor cells, as has been reported
before in the dog,10,11 cat,12 human, 13 pig,14 and sheep.15
In humans, smooth muscle actin (HHF35) has been
Cardiac Rhabdomyosarcoma 211
considered a reliable immunohistochemical marker
for rhabdomyosarcomas, since embryonic rhabdomyo-
blasts are positive for actin before becoming positive
for desmin. 16 In a canine lingual rhabdomyoma, strong
immunoreaction for smooth muscle actin (HHF35)
was observed in neoplastic cells which were devoid
of desmin. 11 In the authors’ case, smooth muscle ac-
tin also was detected in desmin-negative tumor cells.
However, this antigen is not specific to striated muscle
cells since it also has been detected in other mesen-
chymal tumors (e.g., canine leiomyosarcomas, canine
hemangiopericytomas, and myoepithelial cell tumors).17
a
Enzo Diagnostic, Inc., New York, NY
b
Eurodiagnostics, Appeldorn, The Netherlands
References
1. Gonin-Jmaa D, Paulsen DB, Taboada J. Pericardial effusion in a dog
with rhabdomyosarcoma in the right ventricular wall. J Sm Anim Pract
1996;37:193–6.
2. Robinson WF, Maxie MG. The cardiovascular system. Neoplasms of the
heart. In: Jubb KVF, Kennedy PC, Palmer N, eds. Pathology of domestic
animals. Vol. 3. 4th ed. San Diego: Academic Press, 1993:
45–8.
3. Hulland TJ. Tumors of the muscle. In: Moulton JE, ed. Tumors in
domestic animals. 3rd ed. Berkeley: Univ Calif Press, 1990:93–101.
4. Girard C, Hélie P, Odin M. Intrapericardial neoplasia in dogs (abstr). Vet
Path 1996;33:575.
5. Madewell BR, Theilen GH. Tumors of the respiratory tract and thorax.
In: Theilen GH, Madewell BR, eds. Veterinary cancer medicine. 2nd ed.
Philadelphia: Lea & Febiger, 1987:535–65.
6. Camy G. Tumeur intracardiaque (rhabdomyosarcome). Pratique medicale
et chirurgicale de l’animal de compagnie 1986;21(3):229–30.
7. Krotje LJ, Ware WA, Niyo Y. Intracardiac rhabdomyosarcoma in a dog.
J Am Vet Med Assoc 1990;197:368–71.
8. Hall RJ, Cooley DA. Neoplastic disease of the heart. In: Hurst JW, ed.
The heart. 5th ed. New York: McGraw-Hill, 1984:1403–14.
9. Sisson D, Thomas WP, Ruehl WW, Zinkl JG. Diagnostic value of
pericardial fluid analysis in the dog. J Am Vet Med Assoc 1984;184:
51–5.
10. Andreasen CB, White MR, Swayne DE, Graves GN. Desmin as a marker
for canine botryoid rhabdomyosarcomas. J Comp Path 1988;98:23–9.
11. Rivera RYR, Carlton WW. Lingual rhabdomyoma in a dog. J Comp Path
1992;106:83–7.
12. Martín de las Mulas J, Vos JH, Van Mil FN. Desmin and vimentin
immunocharacterization of feline muscle tumors. Vet Path 1992;29:
260–2.
13. De Jong ASH, Van Kessel-Van Vark M, Albus-Lutter CE. Pleomorphic
rhabdomyosarcoma in adults: immunohistochemistry as a tool for its
diagnosis. Hum Path 1987;18:298–303.
14. Vos JH, Borst GHA, Martín de las Mulas J, et al. Rhabdomyosarcomas
in young pigs in a swine breeding farm: a morphologic and immunohis-
tochemical study. Vet Path 1993;30:271–9.
15. Tanaka K, Stromberg PC. Embryonal rhabdomyosarcoma in a sheep. Vet
Path 1993;30:396–9.
16. Erlandson RA. The ultrastructural distinction between rhabdomyosar-
coma and other undifferentiated “sarcomas.” Ultrastruct Path 1987;11:
83–101.
17. Pérez J, Bautista MJ, Rollón E, Chacón-M de Lara F, Carrasco L, Martín
de las Mulas J. Immunohistochemical characterization of hemangio-
pericytomas and other spindle cell tumors in the dog. Vet Path
1996;33:391–7.
 Surgical Reconstruction of Severe
Cicatricial Ectropion in a Puppy
A three-month-old chow chow mixed-breed puppy was presented with severe
cicatricial ectropion of the upper eyelids after being burned maliciously. The burn
wounds healed by second intention with contracture, causing eversion, elevation,
and immobilization of the upper eyelids. The puppy was unable to blink or close the
upper eyelids due to cicatrix (i.e., scar) formation. Surgical repair using tissue-
relaxing procedures was successful in reducing corneal exposure and improving
the puppy’s appearance. J Am Anim Hosp Assoc 1998;34:212–8.

Holly L. Hamilton, DVM, MS, Introduction

Diplomate ACVO
Susan A. McLaughlin, DVM, MS,
Diplomate ACVO
R. David Whitley, DVM, MS,
Diplomate ACVO
Steven F. Swaim, DVM, MS
C Ectropion can be developmental, physiological, or acquired. 1–3
From the Departments of Small Animal
Surgery and Medicine (Hamilton,
McLaughlin, Whitley, Swaim) and the
Scott-Ritchey Research Center (Swaim),
College of Veterinary Medicine,
Auburn University,
Auburn, Alabama 36849-5523.
Doctor Hamilton’s current address is the
Department of Veterinary
Clinical Sciences,
School of Veterinary Medicine,
Louisiana State University,
Baton Rouge, Louisiana 70803-8410.
Ectropion, which is the eversion or rolling out of the eyelid margin,
abnormally exposes the cornea and the palpebral and bulbar conjunc-
tiva. Clinical signs are more frequent with entropion, which is the
rolling in of the eyelid margin, than with ectropion since irritation is
caused by contact of the cornea and conjunctiva with the eyelid hair.1
When clinical signs occur with ectropion, they are secondary to
increased exposure of the cornea and conjunctiva. Marked ectropion
can lead to epiphora, exposure keratitis (i.e., vascularization, pig-
mentation, and scarring of the cornea), and keratinization and hyper-
trophy of exposed conjunctiva. 2,3
Developmental ectropion occurs in many dog breeds (e.g., St. Ber-
nard, bloodhound, mastiff, cocker spaniel) with large palpebral fis-
sures. 1–4 Developmental ectropion most likely is polygenic and is
influenced by genes that define the skin and other structures that
comprise the eyelids, the amount and weight of skin covering the
face, orbital contents, and skull conformation.4 Physiological ectro-
pion is a temporary drooping of the eyelids following concentrated
orbicularis oculi muscle activity in some working-breed dogs with
normal conformation at rest. 2 Acquired ectropion can result from
cicatrix (i.e., scar) formation secondary to surgical, traumatic, ther-
mal, or chemical injury; chronic inflammation; or a combination
thereof. 1 Other causes of acquired ectropion include facial-nerve pa-
ralysis (i.e., paralytic ectropion), trigeminal-induced orbicularis oculi
spasm (i.e., spastic ectropion), and loss of orbicularis oculi muscle
tone in older dogs (i.e., atonic ectropion). 2 Developmental and ac-
quired ectropion occur almost exclusively in the lower eyelid. Cica-
tricial ectropion is the exception, occurring in upper or lower eyelids.2
This case report describes the clinical findings and treatment of a
puppy with severe cicatricial ectropion of the upper eyelids.
Case Report
Four weeks prior to evaluation, the head and body of a three-month-
old, intact male chow chow mixed-breed puppy had been covered
with lighter fluid and ignited. The burn wounds were healing by
second intention, and wound contracture was causing ectropion of
both upper eyelids. Prior to referral, the burn wounds had been treated
by debridement, and the current therapy was sulfadimethoxine

212 JOURNAL of the American Animal Hospital Association

May/June 1998, Vol. 34
Figure 1A
Figure 1B
Figure 1C
Figures 1A, 1B, 1C—A three-month-old chow chow mixed-
breed puppy presented four weeks after malicious burning.
Ulcerated burn wounds and cicatricial ectropion of both upper
eyelids were noted at presentation (A). The conjunctiva of both
eyes is exposed and erythemic. The right eye (B) is less
severely affected than the left eye (C).
ormetoprim a (25 mg/kg body weight, per os [PO]
sid), Carrington wound gel b applied topically to the
skin wounds, triple antibiotic ointmentc (applied to
both eyes [OU], bid), and artificial tear solution d ap-
plied OU as needed to hydrate and lubricate the ex-
posed corneas and conjunctivae.
Cicatricial Ectropion 213
Figure 2—Cicatricial ectropion of both upper eyelids six weeks
after injury. The conjunctiva is erythematous, ecchymotic, and
ulcerated secondary to exposure. Areas of alopecia and scar-
ring are visible on the face.
Both upper eyelids had ectropion with ecchymotic,
erythematous, ulcerated conjunctiva, which was more
severe in the left eye (OS). The upper eyelid margins
were everted and adhered to the eyelid skin. The skin
dorsal to the eyelids was ulcerated with healing, full-
thickness, burn wounds. Widespread alopecia and nu-
merous areas of eschar were present on the bridge of
the nose, dorsum of the head, and periocular areas
[Figures 1A, 1B, 1C]. The upper eyelids were immo-
bile except for mild ventral displacement of the tarsal
plates during attempts to blink. The corneas were
covered partially during blinking by elevation of the
lower and third eyelids. The Schirmer tear test e was
normal in both eyes, and neither cornea retained fluo-
rescein dye. f The remainders of the ophthalmic and
physical examinations were normal. Surgical recon-
struction was postponed and medical management was
continued because the wounds on the head still were
healing and required staged debridement (i.e., escha-
rectomy). Upon reevaluation two weeks later, the ul-
cerated skin wounds were replaced by contracting
scars. The upper eyelid ectropion had not changed
appreciably [Figure 2].
Surgical correction of ectropion is not required in
all cases but is recommended when secondary corneal
or conjunctival lesions occur. 1 In this case, the con-
junctival irritation and abnormal eyelid function war-
ranted surgical repair. Numerous surgical options
exist for ectropion repair. Procedures to correct ec-
tropion secondary to excessive eyelid length or laxity
were not appropriate in this puppy with cicatricial
ectropion. A procedure was needed to release the
cicatricial tissue and to return the eyelids to a more
normal position. Tissue-relaxing procedures (i.e., V-
to-Y plasty,5 Z-plasty 3) and skin flaps or grafts 6,7 were
considered. Although scarring was present, sufficient,
healthy skin was present dorsal to the eyelid to enable
a tissue-relaxing procedure. A V-to-Y plasty was
214 JOURNAL of the American Animal Hospital Association
Figures 3A, 3B, 3C—A V-to-Y plasty of the right upper eyelid.
(A) A V-shaped incision was made dorsal to the right upper
eyelid to include the entire length of the eyelid. (B) Scar tissue
and traction bands were severed and undermined from the
point of the V toward the edge of the eyelid, so the lid could be
advanced and the skin incisions closed without tension. (C) The
incision was closed in a Y configuration.
elected over a Z-plasty because a tissue area the entire
width of the upper eyelid needed to be advanced.
A V-shaped incision was made 1 cm dorsal to the
right upper eyelid margin with the point of the V
away from the eyelid margin [Figures 3A, 3B, 3C].
Scar tissue and traction bands were severed and un-
dermined from the point of the V toward the edge of
the eyelid, so the lid could be advanced and the skin
incisions closed without tension. Care was taken to
preserve the vascular supply to the skin. The incision
was closed in a “Y” with 3-0 nylon g in a simple
interrupted pattern. Sutures were placed alternately
in the arms of the “V” beginning at the ends of the
“V.” When tension became a factor, the remaining
skin edges were sutured to form the stem of the “Y.”
A larger, V-shaped incision was made dorsal to the
more severely affected left eyelid, followed by under-
mining and excision of scar tissue with preservation
of the blood supply as described previously. From the
incision, skin also was undermined dorsomedially and
dorsolaterally, followed by placement of simple in-
terrupted “walking” sutures7 of 2-0 polyglactin 910 h
under the skin to decrease tension and obliterate dead
space while advancing the skin toward the eyelid
margin. The skin was closed with 3-0 nylon in a
simple interrupted pattern in the manner described
for closing the V-to-Y plasty. Conjunctival tacking
sutures of 5-0 polyglactin 910i were placed full-thick-
ness through the left upper eyelid and palpebral con-
junctiva to invert the eyelid margin and retract
redundant palpebral conjunctiva into the fornix. A
partial, temporary tarsorrhaphy was performed in each
eye with horizontal mattress sutures of 4-0 silk j placed
through polyethylene tubing stents to prevent tissue
retraction during healing. Postoperative therapy in-
cluded an Elizabethan collar,k cefadroxyll (11 mg/kg
body weight, PO tid for 14 days), triple antibiotic
ointment c (applied OU, tid), and artificial tear
ointment m (applied OU, as needed).
Topical ophthalmic medications were continued
following suture removal two weeks postoperatively.
May/June 1998, Vol. 34
At reevaluation six weeks postoperatively, the right
upper eyelid had acceptable cosmetic and functional
results with only slight ectropion. The left upper eye-
lid was improved but still had moderate ectropion and
exposed palpebral conjunctiva. The left eyelid mar-
gin remained everted and adhered to the skin of the
upper eyelid. A Schirmer tear test and the remainder
of the ophthalmic examination were normal.
Scarring and contracture continued to cause ectro-
pion of the left eye. Sufficient healthy tissue remained
dorsal to the left upper eyelid to allow a second V-to-
Y plasty. Six weeks after the first surgery, a larger,
V-shaped incision was made extending from dorso-
medial to the medial canthus to dorsolateral to the
lateral canthus of the left eye [Figure 4A]. Scar tissue
under the V-shaped flap was excised. Dissection was
continued to the eyelid margin to remove the scar
tissue causing eversion [Figure 4B]. Skin dorsomedial
and dorsolateral to the “V” incision again was under-
mined, and subcutaneous “walking” sutures of 2-0
polyglactin 910 were used to decrease tension and
dead space while advancing skin toward the eyelid
margin in a Y shape. The V-to-Y plasty was closed as
described previously with 4-0 silk simple interrupted
sutures. This resulted in advancement of the eyelid
margin to a more normal position [Figure 4C]. Con-
junctival tacking sutures of 6-0 polyglactin 910 n were
placed as described previously to invert the eyelid
margin. Temporary tarsorrhaphy sutures of 4-0 silk
were placed to prevent tissues from healing in a con-
tracted position. Postoperative therapy was the same
as the original surgery, except gentamicin sulfate
solutiono (applied OU, bid) replaced the triple antibi-
otic ointment. Sutures were removed after two weeks,
and topical medications were continued.
Five weeks after the second V-to-Y plasty (11
weeks after the initial surgery), the left upper eyelid
had slightly less severe ectropion, but the conjunctiva
remained exposed and was becoming pigmented. The
left upper eyelid had macroblepharon (i.e., an abnor-
mally large eyelid opening) and no mobility [Figure
5A]. The right upper eyelid had almost normal func-
tion and conformation with mild eversion of the
upper eyelid centrally and minimal palpebral con-
junctival exposure [Figure 5B].
Skin graft, skin flap, or another tissue-relaxing
procedure were options considered to correct the ec-
tropion of the left eye. Adequate healthy tissue re-
mained dorsal to the left upper eyelid; therefore, a
Z-plasty 3 in combination with other procedures was
elected. A Z-plasty would result in greater tissue
lengthening but over a narrower area than a V-to-Y
plasty, 3 which was needed at this time. First, a lateral
canthoplasty 8 was performed to decrease the size of
the palpebral fissure. A 1-cm long, full-thickness in-
cision was made in the upper and lower eyelids per-
May/June 1998, Vol. 34 Cicatricial Ectropion 215

Figure 4A Figure 4B

Figures 4A, 4B, 4C—The second V-to-Y plasty of the left upper
eyelid. (A) A V-shaped incision was made dorsal to the left
upper eyelid to include the entire length of the eyelid. (B) After
undermining and dissecting cicatricial tissue, the eyelid as-
sumed a more normal position. (C) Prior to the placement of skin
sutures, “walking” sutures dorsomedial and dorsolateral to the
incision decreased tension and dead space while advancing
tissue to a Y configuration.

pendicular to the margin approximately 1-cm medial

to the lateral canthus [Figures 6A, 6B, 6C]. The upper
eyelid incision was continued in a ventrolateral direc-
tion, and the lower eyelid incision continued in a
dorsolateral direction, creating dorsal and ventral
apexes. The upper and lower eyelid incisions met at
an additional apex lateral to the lateral canthus, creat-
ing a diamond shape. The diamond-shaped region of
skin was excised including the lateral canthus. The
upper and lower eyelid margin incisions were ap-
posed to create a new lateral canthus which was closed
in two layers (with 7-0 polyglactin 910p simple con-
tinuous conjunctival sutures and 4-0 silk simple in-
terrupted skin sutures). Next, an incision was made in
the palpebral conjunctiva along the entire length of
the left upper eyelid 2 mm from and parallel to the
eyelid margin. Scar tissue that was everting the eyelid
margin was released by undermining. This incision
was left to heal by second intention. Conjunctival
tacking sutures of 4-0 polydioxanoneq were used to
invert the eyelid margin as described previously.
Figure 4C
216 JOURNAL of the American Animal Hospital Association
Figure 5A
Figure 5B
Figures 5A, 5B—Five weeks after the second V-to-Y plasty, (A)
the left upper eyelid ectropion is improved slightly, and the
exposed conjunctiva is becoming pigmented. (B) The right
upper eyelid ectropion has been corrected to an almost normal
conformation. Mild eversion of the right upper eyelid centrally
and minimal palpebral conjunctiva are visible. Heavily pig-
mented alopecic skin is present.
Figures 6A, 6B, 6C—A lateral canthoplasty decreased the size
of the palpebral fissure in the left eye. (A) A full-thickness
incision was made in the upper and lower eyelids perpendicular
to the margin. The upper and lower eyelid incisions met at an
additional apex lateral to the lateral canthus, creating a diamond
shape. (B) The upper and lower eyelid margin incisions were
apposed to create a new lateral canthus. Next, an incision was
made in the palpebral conjunctiva parallel to the eyelid margin.
Scar tissue that was everting the eyelid margin was released by
undermining. This incision was left to heal by second intention.
(C) A Z-plasty on the upper eyelid was the tissue-relaxing
procedure chosen for the third surgery on the left eyelid.
May/June 1998, Vol. 34
Figure 7A
Figure 7B
Figures 7A, 7B—A nine-month-old chow chow mixed-breed
puppy was examined nine weeks after lateral canthoplasty and
Z-plasty of the left upper eyelid. (A) The ectropion and
macroblepharon are improved noticeably. Mild central ectro-
pion of the left upper eyelid and exposure of the palpebral
conjunctiva persists. (B) Both eyelids have improved appear-
ance and function. Facial scarring (i.e., alopecia and pigmented
skin) from burn wounds is present.
Tissue relaxation occurs in the direction of the
central limb of a Z-plasty, resulting in lowering of the
retracted upper eyelid margin in this case.7 Thus, the
central limb of a Z was incised perpendicular to and
0.5 cm from the eyelid margin [Figure 6B]. The arms
of the Z incision were the same length as the central
limb (1.5 cm) and at 60˚ angles from the central
limb.7 Tissue was undermined, and the triangular skin
flaps were transposed. The Z-plasty was closed with
4-0 nylon r in a simple interrupted pattern [Figure 6C].
At the tip of each triangular flap, a half-buried hori-
zontal mattress suture was used to help assure blood
supply to the tips of the flaps. A temporary tarsorrha-
phy was performed with 3-0 polypropylene s horizon-
tal mattress sutures through polyethylene tubing
stents. Postoperative therapy included an Elizabethan
collar, cephalexint (22 mg/kg body weight, PO tid),
May/June 1998, Vol. 34
gentamicin sulfate ophthalmic ointmentu (applied OS,
bid), and artificial tear ointment (applied to the right
eye [OD], bid).
Nine weeks after the third surgery (20 weeks after
the initial surgery), the left upper eyelid was im-
proved in appearance and mobility (i.e., ability to
blink). A small amount of palpebral conjunctiva re-
mained exposed [Figures 7A, 7B]. The right eye re-
mained unchanged from the previous visit. Tear
production was normal in both eyes, and neither cor-
nea retained fluorescein dye. The minor remaining
abnormalities in the left upper eyelid were not caus-
ing corneal or appreciable conjunctival disease; there-
fore, no additional surgery was warranted.
Discussion
Thermal burns can be caused by flame, heat, or elec-
tricity and are classified according to their depth.9
Superficial, partial-thickness burns affect only the
epidermis which desquamates and heals by reepithe-
lialization typically in three-to-six days.10 Hair re-
growth usually occurs. Deep, partial-thickness burns
involve the epidermis and various depths of the der-
mis10 with considerable subcutaneous edema and in-
flammatory response. Healing is by reepithelialization
from remnants of deep adnexal structures typically in
three weeks, but the rate of healing and quantity of
hair regrowth depend on the depth of the burn. 10 Full-
thickness burns destroy the entire skin thickness. Su-
perficial subcutaneous vessels are thrombosed and
deeper vessels become excessively permeable, caus-
ing severe subcutaneous edema and gangrene of the
damaged tissue. The burn can extend into underlying
tissues. After removal or slough of the damaged tis-
sue, the wound heals slowly by contraction and
reepithelialization from adjacent skin.9 The puppy in
this report had deep partial-thickness and full-thick-
ness facial burns. Healing of the burns by second
intention caused distortion and ectropion of the upper
eyelids.
The upper eyelid usually is more mobile and more
important in eyelid function (i.e., in protection of the
globe and distribution of tear film) than the lower
eyelid. 11 Almost no upper eyelid mobility was present
in the puppy of this report. The lower and third eye-
lids were able to elevate sufficiently to protect the
globe. This, combined with topical medications, main-
tained corneal health.
A skin graft or a flap had been considered initially
for reconstruction of the left upper eyelid. However,
the risk of flap failure in this patient was considered
unacceptably high due to the probable damage to
blood supply caused by burn wounds. Since some
viable tissue was present in the area, it was decided to
try to move this tissue to correct the ectropion rather
than use a graft in an effort to use the simplest tech-
Cicatricial Ectropion 217
niques first. A V-to-Y plasty and Z-plasty also were
chosen because of their lower risk of failure com-
pared with a graft or flap procedure. Although skin
and cartilage from an inner ear pinna have been
grafted to an eyelid successfully to achieve a func-
tional repair of cicatricial ectropion, 6 the cosmetic
result was not ideal. The puppy in this report had
minimal pinnae remaining due to burn wounds; there-
fore, this procedure was not considered.
Excision of scar tissue and tissue-relaxing proce-
dures were successful in correcting the severe cicatri-
cial ectropion in the puppy reported herein. The less
severe the ectropion is, the easier it is corrected, as
illustrated by the use of a single procedure on the
right eye and the need for multiple procedures on the
more severely involved left eye. The eyelids remain
functional and cosmetically acceptable more than one
year after the final surgery.
a
Primor; Roche, Nutley, NJ
b
Carravet; Carrington Laboratories, Inc., Irving, TX
c
AK-Spore; Akorn, Inc., Abita Springs, LA
d
Akwa tear solution; Akorn, Inc., Abita Springs, LA
e
Schirmer tear test strips; Alcon Laboratories, Fort Worth, TX
f
Fluorets; Smith & Nephew Pharmaceuticals, Ltd., Romford, England
g
3-0 Ethilon; Ethicon, Inc., Somerville, NJ
h
2-0 Vicryl; Ethicon, Inc., Somerville, NJ
i
j
5-0 Vicryl; Ethicon, Inc., Somerville, NJ
4-0 Silk; Ethicon, Inc., Somerville, NJ
k
Buster collar; Jorgen Kruuse, Denmark
l
CefaTabs; Fort Dodge Laboratories, Fort Dodge, IA
m
Akwa tear ointment; Akorn, Inc., Abita Springs, LA
n
6-0 Vicryl; Ethicon, Inc., Somerville, NJ
o
Gentocin ophthalmic solution; Schering-Plough Animal Health, Kenilworth,
NJ
p
7-0 Vicryl; Ethicon, Inc., Somerville, NJ
q
r
4-0 PDS II; Ethicon, Inc., Somerville, NJ
4-0 Ethilon; Ethicon, Inc., Somerville, NJ
s
3-0 Prolene; Ethicon, Inc., Somerville, NJ
t
Cephalexin capsules; Geneva Pharmaceuticals, Inc., Broomfield, CO
u
Gentamicin ophthalmic ointment; Goldline Laboratories, Ft. Lauderdale,
FL
References
1. Gelatt KN. The canine eyelids. In: Gelatt KN, ed. Veterinary ophthal-
mology. 2nd ed. Philadelphia: Lea & Febiger, 1991:268–71.
2. Bedford PGC. Conditions of the eyelids in the dog. J Sm Anim Pract
1988;29:416–28.
3. Bistner SI, Aguirre G, Batik G. Entropion and ectropion. In: Bistner SI,
Aguirre G, Batik G, eds. Atlas of veterinary ophthalmic surgery. Phila-
delphia: WB Saunders, 1977:96–114.
4. Scagliotti RH, Aguirre DG, Cook C, et al. Ocular disorders proven or
suspected to be inherited in dogs. 2nd ed. Baton Rouge: Genetics
Committee, Am Coll Vet Ophth, 1996.
5. Wyman M, Donovan EF, Rudy RL. Surgical correction of cicatricial
ectropion in the dog. Southern Vet 1970;23:5–8.
6. Koening LW, DiPirro E. Surgical correction of ectropion of the lower
eyelid. Vet Med Sm Anim Clin 1970;66:243.
(Continued on next page)
218 JOURNAL of the American Animal Hospital Association May/June 1998, Vol. 34

9. Swaim SF, Henderson RA. Specific types of wounds. In: Swaim SF,
References (cont’d) Henderson RA, eds. Small animal wound management. Philadelphia:
7. Swaim SF, Henderson RA. Management of skin tension. In: Swaim SF, Lea & Febiger, 1990:52–86.
Henderson RA, eds. Small animal wound management. Philadelphia: 10. Bistner SI, Ford RB. Kirk and Bistner’s handbook of veterinary proce-
Lea & Febiger, 1990:134–7. dures and emergency treatment. 5th ed. Philadelphia: WB Saunders,
8. Gross SL. Surgery of the eyelids. In: Bojrab MJ, ed. Current techniques 1995:34–7.
in small animal surgery. 3rd ed. Philadelphia: Lea & Febiger, 1990: 11. Gum GG. Physiology of the eye. In: Gelatt KN, ed. Veterinary ophthal-
68–76. mology. 2nd ed. Philadelphia: Lea & Febiger, 1991:124–61.
 Efficacy of Parathyroid Gland
Autotransplantation in Maintaining Serum
Calcium Concentrations After Bilateral
Thyroparathyroidectomy in Cats
Bilateral thyroidectomy is a commonly indicated treatment for feline hyperthyroidism.
The most common postoperative complication is hypocalcemia due to disruption of
the parathyroid glands. When parathyroid gland disruption is obvious, many authors
suggest autotransplantation (AT) of the glands. This technique never has been
supported by a scientific study which monitored postoperative calcium or parathyroid
hormone (PTH) concentrations. Cats in this study each underwent bilateral
thyroidectomy and parathyroid AT to mimic a clinical situation. Serum calcium
concentrations normalized much quicker than concentrations in previously reported
cats undergoing bilateral thyroidectomy and parathyroidectomy. Parathyroid AT
greatly reduces morbidity in the parathyroidectomized cat.
J Am Anim Hosp Assoc 1998;34:219–24.

Sheldon L. Padgett, DVM, MS Introduction

Karen M. Tobias, DVM, MS,
Diplomate ACVS
Charles W. Leathers, DVM, PhD,
Diplomate ACLAM
K. Jane Wardrop, DVM, MS,
Diplomate ACVP
O hyperthyroid patient, surgical removal of abnormal thyroid tissue
From the Departments of Veterinary
Clinical Sciences (Padgett, Tobias,
Wardrop) and Veterinary Microbiology
and Pathology (Leathers),
College of Veterinary Medicine,
Washington State University,
Pullman, Washington 99164-7060.
The material in this manuscript was
presented at the Annual Meeting of the
American College of Veterinary Surgeons,
San Francisco, California,
November 1996.
Address all reprint requests to
Dr. Padgett,
Rowley Memorial Animal Hospital,
53 Bliss Street,
Springfield, Massachusetts 01105.
Hyperthyroidism is a multisystemic disease caused by an increase in
circulating thyroid hormones. This disease first was confirmed in the
cat in 1979 by Peterson, et al. 1 Since then, it has become the most
commonly diagnosed endocrine disease of the geriatric cat. 2,3 Com-
mon clinical signs of hyperthyroidism include weight loss, polypha-
gia, hyperactivity, tachycardia, polyuria, polydipsia, vomiting, and a
heart murmur.4–8 These signs are a result of increased thyroid hor-
mone levels due to autonomous hormone production by adenomatous
thyroid hyperplasia or, less commonly, a functional thyroid carci-
noma.2,9,10 While multiple methods of treatment exist for the feline
remains the most widely available curative procedure. Bilateral thy-
roidectomy commonly is indicated because this disorder occurs in
both lobes of the thyroid gland in approximately 70% of cases. 3,4,7,11,12
The most serious complication of bilateral thyroidectomy is post-
operative hypocalcemia, reported in 6% to 82% of cats, depending on
the method of thyroidectomy.13–15 Hypoparathyroidism and associ-
ated hypocalcemia result from accidental removal of the external
parathyroid glands or disruption of their vascular supply. The hypo-
calcemia often can be severe and life-threatening, requiring intensive
monitoring and care followed by prolonged supplementation with
calcium and vitamin D analogues. Hypoparathyroidism after bilateral
thyroidectomy can be permanent, although many patients regain cal-
cium homeostasis weeks to months after surgery. 3,5,12 The mechanism
by which these animals regain normocalcemia following thyropara-
thyroidectomy is not certain, but parathyroid hormone (PTH) secre-
tion is unlikely to be the cause. 16
Some authors suggest parathyroid autotransplantation should be
performed if obvious disruption of blood supply to one or both exter-
nal parathyroid glands occurs during surgery.2,3,14,17 Parathyroid au-

JOURNAL of the American Animal Hospital Association 219

220 JOURNAL of the American Animal Hospital Association
totransplantation (AT) involves transferring the ex-
ternal parathyroid gland to another site, usually within
a nearby muscle belly, so that the gland may revas-
cularize and once again become functional. One au-
thor also recommends this as a routine procedure
during unilateral thyroidectomy.18
Parathyroid AT has been studied in several spe-
cies, including cats, dogs, and humans. 19–27 Early
studies reported successful parathyroid autotransplan-
tation in cats. 26,27 Oral calcium supplementation or
high calcium diets were used in these studies to pre-
vent postoperative hypocalcemia after thyroparathy-
roidectomy/AT. Autotransplantation was considered
successful not because calcium concentrations nor-
malized, but because the transplanted tissue survived
histologically. An error in this methodology was
found when Jordan,28 and later Lance,29 reported stud-
ies in which dogs developed profound hypocalcemia
despite histological survival of parathyroid gland
transplants. These results raise the question of whether
the grafts in previous studies actually were functional
and whether those cats would have survived without
oral calcium supplementation.
The purpose of this study was to determine whether
the autotransplanted parathyroid gland would remain
viable and become functional after bilateral thyropara-
thyroidectomy in cats. The authors also sought to
determine if parathyroid AT decreases morbidity (i.e.,
duration or severity of hypocalcemia, or both) after
thyroparathyroidectomy when compared to previous
reports of cats undergoing thyroparathyroidectomy
without AT. The study was designed to mimic the
clinical situation of accidental removal of all parathy-
roid tissue during bilateral thyroidectomy.
Materials and Methods
The following protocol was approved by the local
Institutional Animal Care and Use Committee (IACUC)
prior to initiation of the study. Eight (seven male and
one female), healthy, adult, random-source cats were
used. Preoperative evaluations included a physical
examination, complete blood count, serum biochem-
istry panel, feline leukemia viral antigen testing, and
feline immunodeficiency viral antibody testing. Only
cats with normal physical and hematological param-
eters were included in the study. A serum sample was
collected from each cat prior to the onset of the ex-
periment for later measurement of PTH concentration.
Thyroparathyroidectomy with parathyroid AT was
performed on day zero. Each cat was premedicated
with intramuscular (IM) butorphanol (0.2 mg/kg body
weight) and acetylpromazine (0.05 mg/kg body
weight). Anesthesia was induced with intravenous
(IV) ketamine (5.0 mg/kg body weight) and diazepam
(0.2 mg/kg body weight). Each cat was intubated, and
anesthesia was maintained using halothane in oxygen.
May/June 1998, Vol. 34
Each cat was placed in dorsal recumbency. The
ventral cervical area was shaved and prepared rou-
tinely using chlorhexidine scrub and rinse. A bilat-
eral, extracapsular thyroparathyroidectomy was
performed. Hemostasis was achieved via a combina-
tion of electrocautery and vascular ligation. After
thyroparathyroidectomy, both external parathyroid
glands were identified and dissected free of surround-
ing thyroid tissue. To prevent central necrosis in large
pieces of gland tissue, the glands were sectioned so
that no piece was larger than 3 mm in diameter. A
small portion of each gland was submitted for histo-
logical examination to confirm the parathyroid gland
was transplanted. A recipient bed for the tissue was
made in one of the sternohyoideus muscles by bluntly
dissecting parallel to the muscle fibers. The parathy-
roid gland pieces were placed within the muscle belly.
The myotomy was closed with a simple continuous,
nonabsorbable suture (i.e., silk) to mark the site. An
indwelling, subcutaneous vascular access port then
was placed in the jugular vein contralateral to the
graft site to facilitate collection of multiple blood
samples during the study. Closure of the surgical site
was routine.
Postoperatively, butorphanol (0.2 mg/kg body
weight, IM) and acetylpromazine (0.05 mg/kg body
weight, IM) were administered as needed for analge-
sia and sedation. Cats were monitored continuously
for six days in an intensive care unit (ICU). Signs of
postoperative hypocalcemia and changes in behavior,
appetite, pulse, temperature, respiration, urination,
and defecation were noted. Clinical signs of severe
hypocalcemia were defined as muscle twitching, se-
vere depression, and tetanic seizure-like episodes.
Cats that exhibited these signs were treated by slow,
IV infusion of calcium gluconate (1 ml of a 10%
calcium gluconate solution containing 9.3 mg of ion-
ized calcium administered over 10 min). This was
followed by IV infusion of a calcium gluconate solu-
tion (10 ml of 10% calcium gluconate solution in 250
ml of 0.9% sodium chloride, at 2.5 ml/kg body weight
per hr for eight-to-12 hrs).17,30,31 After day seven, the
cats were housed in the Washington State University
College of Veterinary Medicine Animal Resource Unit.
Blood samples for serum calcium concentrations
and PTH determinations were collected via the vas-
cular access port once a day for six days after sur-
gery, then on days 14, 21, 28, and 35 of the study.
Measurements of calcium concentrations were taken
immediately after blood collection using spectropho-
tometric analysis with Arsenazo III as a reagent. All
serum samples for PTH analysis were frozen at -80˚ C
for measurement at the completion of the study. Hy-
pocalcemia was defined as a serum calcium concen-
tration less than 8.6 mg/dl. Cats showing persistent,
severe hypocalcemia (i.e., serum calcium less than
May/June 1998, Vol. 34
Table 1—Individual serum calcium concentrations for all cats,
days zero through 35. The lower limit for the calcium concentra-
tion reference range is 8.6 mg/dl (dashed line). Thyropara-
thyroidectomy and parathyroid autotransplantation were
performed on study day zero.
6.0 mg/dl) 10 days after surgery were to be supple-
mented with oral calcium.
On study day 35, Group 1 cats (cat nos. 1–4) each
were euthanized with an IV barbiturate overdose. A
complete postmortem examination was performed.
Samples of kidney, liver, small intestine, and heart
were obtained, and these organ systems were exam-
ined for microscopic changes secondary to hypopara-
thyroidism. The muscle containing the parathyroid
gland transplants was evaluated histologically for evi-
dence of graft revascularization and survival of para-
thyroid cells.
Group 2 cats (cat nos. 5–8) were anesthetized on
study day 35. Muscle containing the autotransplanted
parathyroid tissue was removed surgically en bloc,
and the cats were allowed to recover. Anesthetic,
surgical, and postoperative analgesia protocols were
the same as those used during the thyroparathyroidec-
tomy with parathyroid AT procedure. Cats were moni-
tored continuously for six days in an ICU, then moved
to the Animal Resources Unit. The excised parathy-
roid grafts and surrounding muscle tissues were ex-
amined histologically for signs of revascularization
and survival of parathyroid cells.
Following parathyroid graft removal, blood samples
were collected from Group 2 cats daily until study
day 43, then on study days 50 and 59. Serum calcium
concentrations were measured immediately, and se-
rum samples were frozen at -80˚ C for future analysis
of PTH concentration. Twenty-five days after removal
of the autotransplanted parathyroids (study day 60),
the Group 2 cats each were euthanized with an IV
barbiturate overdose, and a complete postmortem ex-
amination was performed with sampling of major or-
gan systems as described for Group 1.
Serum samples collected prior to thyroparathy-
roidectomy/AT; five, 21, and 35 days after thyropara-
thyroidectomy/AT; and 25 days after transplant
Parathyroid Gland Autotransplantation 221
Table 2—Average serum calcium concentrations in cats after
thyroparathyroidectomy and parathyroid autotransplantation
(AT) (n=8). The lower limit for the calcium concentration refer-
ence range is 8.6 mg/dl (dashed line). Thyroparathyroidectomy
and parathyroid AT were performed on study day zero. (An
asterisk [*] represents a statistically significant deviation from
prethyroparathyroidectomy/AT calcium concentrations [p less
than 0.05]).
removal were analyzed for PTH concentration. A
sample collected 17 days after removal of the
autotrans-planted parathyroids (study day 52) was
used for cat no. 7 due to early euthanasia. Samples
were shipped with dry ice. All samples were analyzed
simultaneously at the Michigan State University
Animal Health Diagnostic Laboratory using an in-
tact hormone immunoradiometric assay (IRMA) for
PTH.
Data was analyzed using multiple linear regression
and Bonferroni adjustment, when appropriate, for
multiple comparisons. Statistical significance was
considered to be reached when p was 0.05 or less.
Results
Groups 1 and 2 (Days 0–35)
The average preoperative serum calcium concentra-
tion was 9.54 mg/dl (median, 9.4 mg/dl; range, 9.2 to
10.1 mg/dl). Serum calcium concentrations fell below
normal (less than 8.6 mg/dl) in all cats within 24
hours after surgery [Table 1]. Depression and partial
anorexia were noted in all patients within 48 hours.
Cat no. 2 required parenteral calcium 48 and 96 hours
postoperatively because of muscle twitching and sei-
zure-like tetanic episodes.
The average serum calcium nadir after thyropara-
thyroidectomy/AT was 5.3 mg/dl (median, 5.1 mg/dl;
range, 4.9 to 6.9 mg/dl), with an average decrease of
44.3% from preoperative serum calcium values. The
serum calcium nadir occurred an average of 1.9 days
(median, two days) after thyroparathyroidectomy/AT.
Calcium concentrations on days one through six were
significantly lower than preoperative concentrations
for all cats. There was no significant difference be-
tween preoperative calcium concentrations and cal-
cium concentrations measured on day 14 [Table 2].
222 JOURNAL of the American Animal Hospital Association
Table 3—Group 2 (i.e., cat nos. 5–8) individual serum calcium
concentrations after removal of the parathyroid transplant site.
The lower limit for the reference range is 8.6 mg/dl (dashed
line). Transplant removal was performed on study day 35. Cat
nos. 7 and 8 had histologically confirmed removal of trans-
planted parathyroid tissue.
The serum calcium for seven (88%) of eight cats
returned to the normal range within 21 days (median,
14 days; range, 14 to 21 days) after thyroparathy-
roidectomy/AT. When between-subject analysis was
performed, there were no significant statistical differ-
ences between the rates of recovery from hypocalce-
mia in these seven cats. Cat no. 2 did not regain
normocalcemia before euthanasia at day 35. One se-
rum calcium measurement (day 35) for cat no. 4 was
not included in the analysis due to severe hemolysis
leading to analytic error.
Group 2 (Days 35–59)
After removal of the parathyroid AT site, hypocalce-
mia recurred in all Group 2 cats within 96 hours
[Table 3]. The average serum calcium nadir was 6.3
mg/dl (median, 6.4 mg/dl), with an average decrease
of 37.5% from day 35 mean serum calcium values
(prior to removal of parathyroid AT tissue).
Cat no. 5 was hypocalcemic only once, 96 hours
after graft site removal. Cat no. 6 was hypocalcemic
until 15 days after graft site removal. Hypocalcemia
persisted in two (cat nos. 7, 8) of four cats until the
time of euthanasia. One hypocalcemic cat (cat no. 7)
was euthanized early (17 days after graft removal)
because of vomiting, severe anorexia, and lethargy.
Pathological Findings
Histological evaluation of tissue samples taken at the
time of thyroparathyroidectomy/AT confirmed the
parathyroid gland was biopsied in all cats. No gross
abnormalities were noted in any cat at necropsy.
Samples of kidney, liver, small intestine, and heart
tissues were histologically normal in all cats. The
nonabsorbable braided suture used to mark the site of
transplantation was associated with moderate, local-
ized, neutrophilic inflammation in all samples of
May/June 1998, Vol. 34
Figure 1—Photomicrograph of morphologically normal, trans-
planted parathyroid tissue (arrow) surrounded by skeletal muscle
(Hematoxylin and eosin stain; 81X).
transplant sites removed either at necropsy (Group 1)
or removed en bloc surgically (Group 2).
In four (cat nos. 2, 4, 7, 8) of eight transplant sites,
parathyroid tissue was found within the skeletal
muscle [Figure 1]. No inflammation was associated
with the transplanted parathyroid cells. A scant
amount of fibrous tissue surrounded the parathyroid
tissue, but all parathyroid tissue found was consid-
ered morphologically normal. Parathyroid tissue was
not found in cat nos. 1 and 3 from Group 1 and cat
nos. 5 and 6 from Group 2 on histological evaluation.
In three (cat nos. 2, 3, 4) of eight transplant sites,
thyroid tissue was found and was considered morpho-
logically normal. In cat nos. 2 and 4, the thyroid
tissue was immediately adjacent to the parathyroid
tissue. In cat no. 3, only thyroid tissue was found
without parathyroid tissue in the transplant site.
Parathyroid Hormone Concentrations
Concentrations of PTH (0 to 1 pmol/L; reference
range, 2 to 4 pmol/L) which were not consistent with
clinically normal animals were obtained from samples
taken prior to thyroparathyroidectomy/AT in six of
eight cats. Parathyroid hormone concentration mea-
surements (0 to 2 pmol/L) for samples throughout the
study were uniformly low, with no patterns or trends
identified; therefore, comparison among samples was
not made.
Discussion
The clinical response to total parathyroidectomy has
been documented in cats 16,26,27,32 and other spe-
cies, 16,19,24,33–38 and often mortality was high without
calcium supplementation.19,27,37,38 For this reason, no
control cats (having thyroparathyroidectomy without
parathyroid AT) were included in this study. All cats
in the study reported here became hypocalcemic
within 24 hours of thyroparathyroidectomy, consis-
tent with previous reports.
May/June 1998, Vol. 34
Hypocalcemia in cats after thyroparathyroidectomy
without parathyroid AT was reported previously by
Flanders to persist a median of 71 days, despite daily
oral calcium supplementation. 16 This differs greatly
from the study reported here, in which hypocalcemia
was present for a median of 14 days, and seven of the
eight cats regained normocalcemia within 20 days of
surgery without oral calcium supplementation. Nor-
mocalcemia in these cats most likely was a result of
revascularization of the parathyroid graft.
Cat no. 2 required supplemental calcium and
remained persistently hypocalcemic after thyropara-
thyroidectomy/AT until euthanasia (day 35). Histo-
logically, the graft from cat no. 2 was not different
than other parathyroid grafts evaluated. This cat did
not have the ability to regain normal serum calcium
concentrations, despite revascularization of the para-
thyroid graft. This persistent hypocalcemia suggests
revascularization of the graft may not be the only
event necessary for successful parathyroid AT.
Individual responses to graft site removal varied
among Group 2 cats. After transplant removal, cat
nos. 7 and 8 were profoundly hypocalcemic until eu-
thanasia. The hypocalcemia seen following transplant
removal was of longer duration and was more severe
than that following thyroparathyroidectomy/AT. This,
in combination with histological confirmation of
parathyroid transplant removal, suggests calcium ho-
meostasis was dependent upon the transplanted para-
thyroid gland.
The remaining Group 2 cats (cat nos. 5 and 6)
experienced only mild, transient disturbances in cal-
cium metabolism. Cat no. 5 was hypocalcemic only
once after transplant site removal and otherwise re-
mained normocalcemic until euthanasia. Cat no. 6
remained mildly hypocalcemic (nadir, 7.8 mg/dl) for
14 days after transplant site removal. In these cats,
parathyroid tissue was not found histologically in the
tissue removed from the transplant sites; therefore,
the grafts most likely were left within the cervical
musculature. Transient hypocalcemia may have re-
sulted from vasospasm (in cat no. 5) or from disrup-
tion of blood supply to the parathyroid grafts in situ
(in cat no. 6), as the hypocalcemia was comparable to
that of cats after thyroparathyroidectomy/AT. It is
possible the grafts were not removed because they
had migrated. Extrusion of the graft from the myot-
omy was witnessed and corrected in some cats during
thyroparathyroidectomy/AT. This may have occurred
postoperatively, leading to revascularization in a site
other than the myotomy.
Alternatively, a method of calcium homeostasis
which did not utilize PTH, such as a compensatory
alteration of renal calcium metabolism, may have been
present in cat nos. 5 and 6. This is unlikely because
while thyroparathyroidectomy cats eventually achieve
Parathyroid Gland Autotransplantation 223
normocalcemia independent of PTH, they take a me-
dian of 71 days to do so. 16 Cat nos. 5 and 6 first
achieved normocalcemia 20 days after thyroparathy-
roidectomy/AT, much sooner than would be expected
without dependency on the parathyroid graft.
Transplanted normal thyroid tissue was present in
at least three of eight cats with thyroparathy-
roidectomy/AT; therefore, it may be possible to trans-
plant diseased thyroid tissue in a clinical case. This
may lead to an ectopic site of thyroid adenoma or
adenocarcinoma. In the study reported here, complete
removal of all tissue adhering to the parathyroid gland
was not a priority, but it would be prudent to do so in
clinical cases of hyperthyroidism. Marking the trans-
plant site with a nonreactive, nonabsorbable suture is
recommended to facilitate locating the site in the
future, if necessary.
Parathyroid hormone concentrations were mea-
sured to confirm the parathyroid autotransplant was
functional. As the grafted parathyroid tissue became
functional after AT, increasing concentrations of PTH
would be expected. All blood samples, including those
taken prior to thyroparathyroidectomy/AT, had either
nonexistent or very low concentrations of PTH and
therefore could not confirm graft function or removal.
While low circulating concentrations of PTH may be
expected during graft revascularization immediately
after thyroparathyroidectomy, low PTH concentra-
tions in clinically normal animals prior to thyropara-
thyroidectomy make the PTH data suspect. All
samples for PTH analysis were stored at -80˚ C for
90-to-180 days until the study was completed. Para-
thyroid hormone is stable when stored at -20˚ C for
four weeks or during repeated freeze/thaw cycles. 39
The IRMA used has been validated in the cat and has
a sensitivity of 3.90 pg/ml (International System of
Units [SI] conversion, 0.41 pmol/L). 39 While a lower
sensitivity would have been ideal, no commercially
available IRMA validated in the cat has been found to
be superior. Thus, the low concentrations of PTH
obtained make preanalytic or analytic error likely.
The source of error in the PTH concentration mea-
surements may have been the delay between sample
collection and frozen storage at -80˚ C. Sometimes
samples were not frozen immediately at -80˚ C but
instead were stored temporarily at -4˚ C. Parathyroid
hormone concentrations have been shown to decrease
in a matter of hours even when frozen at 0˚ C. 39 While
proper PTH assay results would have supported the
data presented in this report, measurement of calcium
concentrations provided significant evidence for the
efficacy of parathyroid AT.
As opposed to previous reports in cats, this study
uses calcium concentrations to support the success of
parathyroid AT. Cats undergoing thyroparathy-
roidectomy regained normocalcemia much faster with
224 JOURNAL of the American Animal Hospital Association
AT (median, 14 days) than cats without AT (median,
71 days 16). Normocalcemia was accomplished with-
out oral calcium supplementation. The authors, there-
fore, propose that AT of parathyroid tissue markedly
decreases morbidity in the acutely aparathyroid cat.
Following disruption of the external parathyroid
glands, most cases receiving parathyroid AT will have
a dramatically decreased duration of hypocalcemia
when compared to cases without parathyroid AT.
The purpose of this study was to evaluate parathy-
roid AT after bilateral thyroparathyroidectomy. The
authors do not suggest parathyroid AT as a method of
treatment for feline hyperthyroidism; therefore, com-
parisons are not made to other methods of treatment
for this disease. The parathyroid AT procedure de-
scribed is suitable for clinical use after accidental
parathyroid disruption, although using a nonreactive
suture to close the myotomy may decrease potential
inflammatory damage to the graft. The authors also
recommend thorough removal of all thyroid tissue
from the parathyroid gland being transplanted to pre-
vent iatrogenic transplantation of abnormal thyroid
tissue. Parathyroid AT does not preclude the need for
careful postoperative monitoring, as clinically impor-
tant hypocalcemia still occurs.
References
1. Peterson ME, Johnson GF, Andrews LK. Spontaneous hyperthyroidism
in the cat. Proceed, Am Coll Vet Int Med 1979:108.
2. Peterson ME, Randolph JF, Mooney CT. Endocrine diseases. In: Sherding
RG, ed. The cat: diseases and clinical management. 2nd ed. New York:
Churchill Livingstone, 1994:1403–506.
3. Feldman EC. Feline hyperthyroidism (thyrotoxicosis). In: Feldman EC,
Nelson RW, eds. Canine and feline endocrinology and reproduction. 2nd
ed. Philadelphia: WB Saunders, 1996:118–66.
4. Peterson ME, Kintzer PP, Cavanagh PG, et al. Feline hyperthyroidism:
pretreatment clinical and laboratory evaluation of 131 cases. J Am Vet
Med Assoc 1983;183:103–10.
5. Salisbury SK. Hyperthyroidism in cats. Comp Cont Ed Pract Vet
1991;9:1399–409.
6. Liu S, Peterson ME, Fox PR. Hypertrophic cardiomyopathy and hyper-
thyroidism in the cat. J Am Vet Med Assoc 1984;185:52–7.
7. Thoday KL, Mooney CT. Historical, clinical and laboratory features of
126 hyperthyroid cats. Vet Rec 1992;131:257–64.
8. Broussard JD, Peterson ME. Changes in clinical and laboratory findings
in cats with hyperthyroidism from 1983–1993. J Am Vet Med Assoc
1995;206:302–5.
9. Peter HJ, Gerber H, Studer H, Becker DV, Peterson ME. Autonomy of
growth and of iodine metabolism in hyperthyroid feline goiters trans-
planted onto nude mice. J Clin Invest 1987;80:491–8.
10. Hoenig M, Goldschmidt MH, Ferguson DC, Koch K, Eymontt MJ. Toxic
nodular goitre in the cat. J Sm Anim Pract 1982;23:1–12.
11. Peterson ME, Becker DV. Radionuclide thyroid imaging in 135 cats with
hyperthyroidism. Vet Radiol 1984;25:23–7.
12. Peterson ME, Turrel JM. Feline hyperthyroidism. In: Kirk RW, ed.
Current veterinary therapy IX. Philadelphia: WB Saunders, 1986:
1026–33.
13. Welches CD, Scavelli TD, Matthiesen DT, Peterson ME. Occurrence of
problems after three techniques of bilateral thyroidectomy in cats.
Vet Surg 1989;18:392–6.
14. Birchard SJ, Peterson ME, Jacobson A. Surgical treatment of feline
hyperthyroidism: results of 85 cases. J Am Anim Hosp Assoc
1984;20:705–9.
May/June 1998, Vol. 34
15. Flanders JA, Harvey HJ, Erb HN. Feline thyroidectomy: a comparison of
postoperative hypocalcemia associated with three different surgical
techniques. Vet Surg 1987;16:362–6.
16. Flanders JA, Neth S, Erb HN, Kallfelz FA. Functional analysis of ectopic
parathyroid activity in cats. Am J Vet Res 1991;52:1336–40.
17. Flanders JA. Surgical treatment of hyperthyroid cats. Mod Vet Pract
1986;67:711–5.
18. Norsworthy GD. Feline thyroidectomy: a simplified technique that
preserves parathyroid function. Vet Med 1995;90:1055–63.
19. Paton DN, Findlay L. The parathyroids: tetania parathyreopriva: its
nature, cause and relations to idiopathic tetany. Q J Exp Physiol
1916;10:203–31.
20. Niederle B, Roka R, Brennan MF. The transplantation of parathyroid
tissue in man: development, indications, technique, and results.
Endocr Rev 1982;3:245–79.
21. Paloyan E, Lawrence AM, Paloyan D. Successful autotransplantation of
the parathyroid glands during total thyroidectomy for carcinoma.
Surg Gynecol Obstet 1977;145:364–8.
22. Saxe A. Parathyroid transplantation: a review. Surgery 1984;95:507–26.
23. Shaha AR, Burnett C, Jaffe BM. Parathyroid autotransplantation during
thyroid surgery. J Surg Oncol 1991;46:21–4.
24. Wells SA, Burdick JF, Christiansen CL, et al. Long-term survival of
dogs transplanted with parathyroid glands as autografts and as allografts
in immunosuppressed hosts. Transplantation Proceedings 1973;
V:769–71.
25. Cole JA, Forte LR, Thorne PK, et al. Autotransplantation of avian
parathyroid glands: an animal model for studying parathyroid function.
Gen Comp Endocrinol 1990;76:451–60.
26. Christian M, Christiani H. De la persistance des graffes des glandes
parathyreoides. Compt Rend Soc de Biol 1905;1:754.
27. Swingle WW, Nicholas JS. An experimental and morphological study of
the parathyroid glands of the cat. Am J Anat 1925;34:469–509.
28. Jordan GL, Foster RP, Gyorkey F. Transplantation of parathyroid glands.
Transplant Bull 1958;5:392.
29. Lance EM. A functional and morphological study of intracranial para-
thyroid allografts in the dog. Tranplantation 1967;5:1471.
30. Peterson ME. Hypoparathyroidism. In: Kirk RW, ed. Current veterinary
therapy IX. Philadelphia: WB Saunders, 1986:1039–45.
31. Chew DJ, Nagode LA, Carothers M. Disorders of calcium: hypercalce-
mia and hypocalcemia. In: DiBartola SP, ed. Fluid therapy in small
animal practice. Philadelphia: WB Saunders, 1992:116–76.
32. von Eiselberg AF. Ueber erfolgreiche einheilung der katzenschilddruse
in die bauchdecke und auftreten vontetanie nach deren exstirpation.
Weien Klin Wochenschr 1892;26:81–5.
33. Wells SA, Burdick JF, Ketcham AS, et al. Transplantation of the
parathyroid gland in dogs. Transplantation 1973;15:179–82.
34. Cattell R. Parathyroid transplantation, a report of autografts of parathy-
roid glands removed during thyroidectomy. Am J Surg 1929;VII:4–8.
35. Kerr D, Skinner DW, Hosking DJ, et al. Maintenance of serum calcium
after total thyroparathyroidectomy. Eur J Surg Oncol 1990;16:436–42.
36. Shambaugh P. Autotransplantation of parathyroid gland in the dog, an
evaluation of Halsted’s law of deficiency. Arch Surg 1936;32:709–20.
37. Shapiro S, Jaffe HL. On the occurrence of accessory parathyroids and
their relation to survival of animals after parathyroidectomy.
Endocrinology 1923;7:720–4.
38. Jacob SW, Rastegar MJ. Studies in adaptation to acute parathyroid
deficiency. J Am Med Assoc 1963;183:111–2.
39. Barber PJ, Elliott J, Torrance AG. Measurement of feline intact parathy-
roid hormone: assay validation and sample handling studies.
J Sm Anim Pract 1993;34:614–20.
 Complications Associated with the
Implantation of Polypropylene Mesh in
Dogs and Cats: A Retrospective Study
of 21 Cases (1984–1996)
Complications associated with implantation of polypropylene mesh in dogs and
cats were evaluated retrospectively. Immediate postoperative complications were
common (in 10 of 20 cases) but predominantly involved seroma formation which
resolved with treatment. The only long-term (i.e., six months or more) complication
identified was mass recurrence at the site of tumor resection (in seven of 14 cases).
Recurrence was affected by resection size. The average number of ribs resected in
cases of thoracic wall neoplasia (with and without mass recurrence) was 1.8 and
3.5, respectively. In this study, implantation of polypropylene mesh facilitated the
reconstruction of large tissue defects and was not associated with any serious
complications. J Am Anim Hosp Assoc 1998;34:225–33.

Kerri L. T. Bowman, DVM Introduction

Stephen J. Birchard, DVM, MS,
Diplomate ACVS
Ronald M. Bright, DVM, MS,
Diplomate ACVS
RS
From the Department of Veterinary
Clinical Sciences (Bowman, Birchard),
College of Veterinary Medicine,
The Ohio State University,
601 Vernon L. Tharp Street,
Columbus, Ohio 43210 and the
Department of Small Animal Clinical
Sciences (Bright),
College of Veterinary Medicine,
University of Tennessee,
P. O. Box 1071,
Knoxville, Tennessee 37901-1071.
Doctor Bowman’s current address is the
Department of Small Animal Surgery
and Medicine,
College of Veterinary Medicine,
Auburn University,
Auburn, Alabama 36849.
In dogs and cats, large body wall defects can result from resection of
tumors, severe trauma, or hernias. Autogenous tissue is preferred to
close these defects; however, adequate local tissue frequently is not
available, and harvest of local or distant autogenous tissue may re-
quire a more lengthy procedure or multiple surgeries. In humans, the
increased length of surgical procedure is associated with a higher rate
of morbidity and mortality.1 Alternatives to autogenous tissue flaps
or implants are synthetic implants like polypropylenea,b mesh [Figure
1]. Other types of synthetic mesh implants are available, but polyprop-
ylene is preferred by many surgeons because of its strength and ease
of handling.
Implantation of polypropylene mesh in experimental dogs has been
studied. 2,3 Polypropylene mesh has been found to be well tolerated by
surrounding tissue. However, few clinical studies have been done to
evaluate the use of polypropylene mesh in small animals. Previous
reports in the literature have evaluated implantation of polypropylene
mesh in the closure of thoracic wall, abdominal wall, skull, and
tracheal defects in dogs. 4–8 However, only one study described the
use of polypropylene mesh in a large number of clinical cases. In that
study, the authors evaluated the repair of chest wall defects following
en bloc resection of primary rib tumors. In the immediate postopera-
tive period (defined as the first five days after surgery), no incisional
complications were associated with closure of the thoracic wall defect. 6
To the authors’ knowledge, no reports in the literature primarily
evaluate the immediate and long-term postoperative complications
associated with the implantation of polypropylene mesh in dogs and
cats. The purpose of this study was to examine the results of polyprop-
ylene mesh implantation in clinical cases for reconstruction of tissue
defects. The authors’ hypothesis was that polypropylene mesh was
efficacious in tissue defect repair with no long-term, adverse
sequelae.

JOURNAL of the American Animal Hospital Association 225

226 JOURNAL of the American Animal Hospital Association
Figure 1—The polypropylene meshesa,b used in this study are
available from the manufacturers in sheets which can be auto-
claved and custom sized by the surgeon during the reconstruc-
tive surgery.
Materials and Methods
The medical records from 1984 through 1996 of The
Ohio State University Veterinary Teaching Hospital
(OSUVTH) and the University of Tennessee Veteri-
nary Medical Teaching Hospital (UTVMTH) were
reviewed for cases in which polypropylene mesh was
implanted. Nineteen animals (21 mesh implant cases)
were found. Information obtained from the medical
records included signalment, history, diagnostics, sur-
gical procedure, immediate postoperative complica-
tions (prior to release from the hospital), final
diagnosis, date of release, and long-term follow-up.
Except in the description of signalment, each mesh
implantation was regarded as an individual case for
the determination of results.
The sterile polypropylene mesh implants were
placed according to a previously described technique.4
A sheet of autoclaved polypropylene mesh was tai-
lored to a size slightly larger than the defect so that
when turned over at the edge, it would result in a
double-thickness margin of approximately 1 cm
around the entire periphery of the prosthesis. In the
majority of cases, the mesh was folded such that the
cut edge was external to the body cavity. The mesh
then was sutured into place under slight tension using
a monofilament suture such as polypropylene, c
polydioxanone,d or polyethylene. Soft-tissue cover-
age was acheived by undermining and transposing the
local musculature, subcutaneous tissue, and skin.
Omentum was not used in any of the cases to augment
the soft-tissue coverage.
Follow-up information was obtained from the
medical record or via a telephone interview with the
owner or referring veterinarian. Questions asked dur-
ing the telephone interview were intended to deter-
mine the present clinical condition and if any
complications had occurred since the last visit to The
OSUVTH or the UTVMTH. Long-term follow-up
was defined as six months or more since the date
of surgery.
May/June 1998, Vol. 34
Results
Signalment
Sixteen dogs and three cats underwent polypropylene
mesh implantation [see Table]. Two dogs each re-
ceived two separate mesh implants. The canine breeds
most frequently represented were mixed-breed dogs
(n=6) and golden retriever (n=3). All of the cats were
domestic shorthairs. The median age at presentation
was 8.5 years (range, 2.5 to 13 years). Of the dogs,
eight were male and eight were female. Of the cats,
two were male and one was female.
Clinical Presentation
The presenting complaint in 18 cases was a body wall
mass (in the thoracic wall in 14 cases and in the
abdominal wall in four cases). Of the remaining three
cases, one had a chronic ventral incisional hernia, one
had a chronic diaphragmatic hernia, and the third had
a chronic perineal hernia. The median duration of
clinical signs prior to presentation was 2.75 weeks
(range, one day to 1.5 years).
Fourteen cases had undergone surgery prior to pres-
entation. In five cases, the animals had incisional
biopsies performed to determine the tumor types. The
other nine cases had undergone corrective procedures,
either to remove the tumor (n=6) or primarily to close
a hernia (n=3).
Presurgical Evaluation
Prior to surgery at The OSUVTH or the UTVMTH,
baseline complete blood counts (CBCs) and biochemi-
cal profiles were performed in all 21 cases. Five cases
had abnormalities on their CBCs. The most common
abnormality was a leukocytosis with an increased
number of mature and immature neutrophils (i.e., re-
generative left shift) in four of five cases. Seventeen
of the 21 biochemical profiles were normal. Three
cases had minor abnormalities which required no
change in the surgical plan or continued monitoring.
One case had a decreased blood glucose which was
monitored pre- and postoperatively. The primary
cause of the hypoglycemia was not determined.
Thoracic radiographs were obtained in all cases
with thoracic or abdominal wall masses [Figure 2]. In
three cases, equivocal evidence of pulmonary me-
tastasis was identified prior to surgery; however, sub-
sequent radiographs did not confirm pulmonary
metastasis.
Surgical Procedure
Of the 14 thoracic wall reconstructions, the number
of ribs resected was one rib (n=3), two ribs (n=2),
three ribs (n=5), four ribs (n=3), or five ribs (n=1).
The defects in other areas varied and ranged in size
from 2 by 6 cm to 15 by 25 cm.
 Table
Results of Implantation of Polypropylene Mesh in 19 Dogs and Cats*

Case Age Weight

No. Species Breed (yrs) Sex† (lbs) Presenting Complaint Final Diagnosis Immediate Follow-Up Long-Term Follow-Up
May/June 1998, Vol. 34

1 Feline Domestic 10 MC 13 Left thoracic wall mass, Fibrosarcoma No complications 7 mos, mass palpable at
shorthair 3 mos’ duration original tumor site;
8 mos, euthanized;
necropsy
histopathology,
myxofibrosarcoma
2 Canine Mixed-breed 10 M 41 Left thoracic wall mass, Osteosarcoma Seroma 3 days 2 mos, no recurrence or
dog 3-to-4 mos’ duration postsurgery, mesh complications,
conservative treatment lost to follow-up
3 Canine Irish setter 9 F 66 Right thoracic wall mass, Chondroma/ Elevated temperature 1 mo, mass palpable at
unknown duration chondrosarcoma (104˚ F) the day of original tumor site;
surgery, antibiotics 7 mos, died, no
administered for 3 days histopathology
4 Feline Domestic 3.5 FS 7.5 Right thoracic wall mass, Aneurysmal bone No complications 7.5 mos, no recurrence or
shorthair 2.5 mos’ duration cyst mesh complications
5 Canine Mixed-breed 11 FS 58 Right thoracic wall mass, Chondrosarcoma Seroma 2 days 6.5 mos, mass palpable
dog 2 wks’ duration postsurgery, at original tumor site;
conservative treatment euthanized, no
histopathology
6 Canine German 13 M 68 Draining mass right Hemangiosarcoma Died 36 hours post- Not applicable
shorthaired thoracic wall, 6 mos’ surgery due to cardiac
pointer duration and respiratory arrest,
no complications prior
to arrest
7 Canine Golden 8 FS 71 Right thoracic wall mass, Osteosarcoma Seroma 3 days post- No follow-up available
retriever 8-to-9 days’ duration surgery, conservative after release
therapy
8 Canine Mixed-breed 7 FS 23 Left thoracic wall mass, Poorly differentiated No complications Euthanized 3 days after
dog 2 wks’ duration spindle cell release
sarcoma
9 Canine Mixed-breed 11.5 MC 60 Right thoracic wall mass, Osteochondroma Seroma 3 days post- 10 mos, mass palpable at
dog 7 days’ duration (atypical surgery, treated by original tumor site; see
chondroma) placement of Penrose case no. 10
drains, pulled in 2 days
Polypropylene Mesh

(Continued on next page)

227
 Table (cont’d) 228

Results of Implantation of Polypropylene Mesh in 19 Dogs and Cats*

Case Age Weight

No. Species Breed (yrs) Sex† (lbs) Presenting Complaint Final Diagnosis Immediate Follow-Up Long-Term Follow-Up
10 See case See case See case no. 9 Regrowth at old surgery Chondrosarcoma No complications 10 mos, no recurrence or
no. 9 no. 9 site, right thorax, mesh complications
3 wks’ duration
11 Canine Mixed-breed 4 MC 84 Chronic incisional hernia, Chronic incisional Seroma 3 days post- 54 mos, no recurrence or
dog 2.5 mos since last hernia surgery, treated by mesh complications
surgery placement of Penrose
drains, pulled in 5 days
12 Canine Standard 7 FS 19 Multiple masses left flank, Hemangiosarcoma No complications 15 mos, mass palpable at
schnauzer 2 wks’ duration original tumor site; see
case no. 13
13 See case See case See case no. 12 Mass at previous incision, Granulomatous No complications 24 mos, no recurrence or
no. 12 no. 12 2 wks’ duration myositis, foreign mesh complications
material, fibrosis
14 Feline Domestic 5 MC 12 Left flank mass, 1 days’ Fibrosarcoma Subcutaneous 14 mos, mass palpable at
JOURNAL of the American Animal Hospital Association

shorthair duration emphysema 1 day original tumor site, lost

postsurgery, no treat- to follow-up, no
ment needed histopathology
15 Canine Golden 3.5 FS 92 Left thoracic wall mass, Chrondrosarcoma Seroma 3 days post- 24 mos, no recurrence or
retriever 8 wks’ duration surgery, treated with mesh complications
warm compresses and
bandaging; septic pleural
effusion and increased
body temperature, treated
with thoracic drains
and antibiotics
16 Canine Golden 8.5 MC 87 Left/ventral abdominal Infiltrative lipoma Seroma 4 days post- 21 mos, no recurrence or
retriever wall mass, 3 wks’ surgery, treated with mesh complications
duration open drainage and
bandaging
17 Canine Siberian 2.5 M 51 Chronic diaphragmatic Chronic No complications 17 mos, no recurrence or
husky hernia, 3 mos’ duration diaphragmatic mesh complications
hernia
18 Canine English 12 FS 50 Right caudal thoracic wall Hemangio- Seroma 2 days post- 6 mos, no recurrence or
springer mass, 10 days’ duration pericytoma surgery, conservative mesh complications
spaniel treatment
May/June 1998, Vol. 34
 May/June 1998, Vol. 34

Table (cont’d)
Results of Implantation of Polypropylene Mesh in 19 Dogs and Cats*

Case Age Weight

No. Species Breed (yrs) Sex† (lbs) Presenting Complaint Final Diagnosis Immediate Follow-Up Long-Term Follow-Up
19 Canine Afghan 9 MC 62 Right axillary mass, Osteosarcoma No complications 14 mos, no recurrence or
hound unknown duration mesh complications
20 Canine English 6 F 46 Right thoracic wall mass, Chondroma No complications 71 mos, mass resected
pointer 2-to-3 wks’ duration from original site, no
histopathology; 93 mos,
mass at original site, no
histopathology
21 Canine Mixed-breed 10 MC 57 Recurrent left perineal Chronic perineal No complications 10 mos, no recurrence or
dog hernia, 6 mos’ duration hernia mesh complications

* Each implant was considered an individual case; 21 implants were placed

†
MC=castrated male; M=male; F=female; FS=spayed female
Polypropylene Mesh
229
230 JOURNAL of the American Animal Hospital Association
Figure 2—Preoperative lateral thoracic radiograph from case
no. 15, a 3.5-year-old, spayed female golden retriever with a
chondrosarcoma of the left thoracic wall (arrow).
The mesh was sutured to the adjacent tissue using
polypropylene in 16 cases, polydioxanone in four
cases, and polyethylene in one case. Suture size var-
ied from 0 to 4-0.
Antibiotics were administered either before anes-
thesia, at induction of anesthesia, or intraoperatively
in all but four cases. The specific antibiotic chosen
varied, but except for one case it was always one of
the cephalosporins. In two cases, antibiotic therapy
was instituted one-to-two days prior to surgery. In
one of these cases, the animal had a chronic incisional
hernia from which Pseudomonas aeruginosa was cul-
tured at the time of mesh implantation. The other had
a thoracic mass which had been draining prior to
presentation. Both cases exhibited a regenerative left
shift on their preoperative CBCs. Of the four cases
that did not receive antibiotics perioperatively, one
developed a mildly elevated temperature (104˚ F)
within 24 hours postsurgery with no other clinical
signs or evidence of infection. However, the animal
was placed on postoperative antibiotic therapy for
three days and the fever resolved.
Thoracic drain tubes were placed in nine (60%) of
the 15 cases in which the thoracic cavity was entered.
The average time to removal was two days (range,
one to three days) after surgery. Penrose drains were
placed intraoperatively at the incision sites in four
cases. They were removed an average of four days
(range, two to six days) after surgery.
Histopathology Results
Biopsies were obtained at surgery in 18 of 21 cases
[Figure 3]. The only cases in which biopsies were not
obtained were the chronic incisional hernia, the
chronic diaphragmatic hernia, and the chronic perineal
May/June 1998, Vol. 34
Figure 3—En bloc excision of the chondrosarcoma (arrowhead)
involving the distal segments of the left third to sixth ribs in
case no. 15 (radiograph in Figure 2).
hernia. The biopsy results are listed in the Table.
Histopathology on 12 of the 18 biopsies were consis-
tent with malignant neoplasia. The margins of the
histopathology specimens were evaluated for com-
pleteness of excision. All of the neoplasms appeared
to be excised completely except in a dog with poorly
differentiated spindle-cell sarcoma of the thoracic
wall.
Immediate Postoperative Evaluation
The immediate postoperative period was defined as
the time from surgery to release from the hospital.
One case (case no. 6 with a thoracic wall mass) suf-
fered respiratory and cardiac arrest and died within
36 hours of surgery due to unknown causes. No
incisional problems had been noted prior to death, but
because the animal never was released from the hos-
pital it was not included in evaluation of complications.
Ten (50%) of 20 surviving cases developed com-
plications in the immediate postoperative period in-
cluding seroma formation, elevated temperature, and
subcutaneous emphysema. Development of compli-
cations had a minimal effect on length of hospital
stay. The average hospital stay after surgery was 5.1
days (range, two to 11 days). The average hospital
stay for those cases which developed complications
was 5.8 days (range, two to 11 days). For those cases
that did not develop complications, the average hos-
pital stay was 4.3 days (range, two to nine days).
Penrose drains were placed at the time of surgery
in four cases. The average time to removal of the
Penrose drain was four days. None of these cases
developed seromas. Seromas developed in eight (50%)
of the 16 cases in which Penrose drains were not
placed during surgery. Diagnosis of seromas was
made by gross appearance of a fluctuant mass in the
subcutaneous space under the incision, without other
evidence (e.g., heat or pain over the mass) suggestive
May/June 1998, Vol. 34
Figure 4—Two-year postoperative appearance of the golden
retriever (case no. 15) following en bloc resection of a thoracic
wall chondrosarcoma and polypropylene mesh implantation. No
visible or palpable defect of the thoracic wall was detected.
of abscessation. No other incisional complications
were observed in the seroma cases. In two cases, it
was necessary to place Penrose drains in the seroma.
The discharge from the drains was serous in both
cases. In one case, the drain was removed in two
days. In the second case, the drain was removed five
days after placement. Five of the other six cases with
seromas were treated conservatively by application
of warm compresses or bandaging. In the remaining
case, the seroma was drained by partially opening the
incision, followed by bandaging. The drainage ob-
served in the bandage was serous. Seromas did not
remain as chronic problems in any of these cases.
Only one seroma case had an elevated temperature.
This animal was diagnosed with suppurative pleural
effusion. Therefore, a correlation between seroma for-
mation and increased temperature did not exist.
One case (case no. 14) that had mesh applied to the
flank region developed subcutaneous emphysema that
did not require treatment. On reevaluation 14 days
after surgery, a small seroma was present which was
managed conservatively (with warm compresses) and
then resolved.
Clinical signs of incisional infection did not de-
velop in any of the cases. Case no. 11 had a chronic
incisional hernia, and Pseudomonas aeruginosa was
cultured from the surgical site at the time of mesh
implantation. The animal was placed on norfloxacin, e
and no signs of systemic or incisional infection were
detected.
Case no. 15 developed signs of systemic infection
in the immediate postoperative period. In this case,
polypropylene mesh was implanted after partial re-
section of four ribs. The animal’s temperature in-
creased to 105.l˚ F three days after surgery. Pleural
effusion was seen on thoracic radiographs. Cytology
of the effusion was diagnostic of a septic suppurative
Polypropylene Mesh 231
exudate. A thoracic drain tube was placed, and antibi-
otic therapy was administered using intravenous
cefazolin sodium f for six days followed by oral
cefadroxil g for seven days. The thoracic tube was
removed five days after placement when resolution of
the pleural effusion was evident on thoracic radio-
graphs. Once signs (i.e., pleural effusion and fever)
of infection resolved, the animal had no further com-
plications associated with the mesh or the pyothorax
(follow-up, 24 months).
Long-Term Evaluation
Long-term follow-up was defined as six months or
more postoperatively. The median long-term follow-
up was 14 months (range, six to 93 months). Seven-
teen (81%) of the 21 cases had follow-up of six
months or more. Of the remaining cases, one animal
died in the hospital; one case which was diagnosed
with an incompletely excised, poorly differentiated
spindle cell sarcoma was euthanized within one week
of release from the hospital for unknown reasons; and
two cases were lost to follow-up.
None of the 17 cases which were followed six
months or longer postoperatively developed any com-
plications associated with the mesh [Figure 4]. In
seven (50%) of 14 cases with tumors, masses recurred
at the original sites. The median disease-free interval
was 14 months (range, one to 71 months). Excisions
of the recurrent masses were performed in three of
these seven cases. Polypropylene mesh was needed to
close the resultant defects in two cases. One animal
originally was diagnosed as having an osteochon-
droma, and only part of one rib was resected during
the original surgery. The subsequent surgical excision
involved the partial removal of four ribs. Chondrosar-
coma was diagnosed by histopathological evaluation
of this tissue and the original mesh implant. The other
case that had mesh implanted at the second resection
had a hemangiosarcoma of the left flank. At the second
surgery, another section of body wall was removed,
not including the original mesh. The histopathologi-
cal description of this tissue was multifocal granu-
lomatous myositis with intralesional foreign material
and fibrosis of the abdominal wall. No histopathol-
ogy was available on the third case.
Discussion
The reconstruction of large tissue defects has been a
challenge to both human and veterinary surgeons.
Numerous reports in the human literature describe the
use of autogenous tissue for the reconstruction of
tissue deficits. 9–11 Pedicle grafts and grafts of omen-
tum, peritoneum, rectus fascia, fascia lata, latissimus
dorsi muscle, rectus abdominus muscle, external ab-
dominal oblique muscle, pericardium, and bone have
been utilized. In humans, it is believed that the addi-
232 JOURNAL of the American Animal Hospital Association
tional surgical time required for the harvest of these
tissues results in an increased rate of morbidity and
mortality. 1 Synthetic materials have the advantages
of being readily available and easily tailored to the
surgeon’s needs. Properties possessed by the ideal
synthetic prosthesis include hypoallergenicity, lack
of carcinogenicity and inflammatory response, ability
to withstand sterilization, resistance to modification
by body fluids, and adequate strength. 12 Although a
number of synthetic mesh implants have been evaluated
over the last 40 years on the basis of both experimental
and clinical properties,2,3,13–15 polypropylene mesh re-
mains one of the most frequently used mesh implants.
Polypropylene possesses high tensile strength and
low permeability to liquids and gases. It has a highly
crystalline molecular structure which imparts a high
softening temperature. This allows polypropylene to
be sterilized by usual operating room procedures with-
out affecting its tensile strength.6
Polypropylene mesh is produced when the mono-
filaments of the polymer are woven in a taffeta pat-
tern. The taffeta weave gives the mesh strength and
prevents raveling. 2 Since polypropylene mesh is made
from a monofilament, it does not possess any interfi-
ber pores. As a result, all of its pores are large (200-
to-800 µm) when compared with other types of
mesh. 17 It has been shown experimentally that pore
sizes greater than 100 µm are required for rapid in-
growth of vascularized connective tissue.18 Small pore
sizes do not provide sufficient space for capillary
penetration. 19 Polypropylene mesh is infiltrated uni-
formly with fibrous tissue to a 3- to 4-mm thickness
at six weeks postimplantation.2 In an experimental
infected model, healthy granulation tissue covered
the mesh by the 14th-to-21st postoperative day.2 At
necropsy, the fibrous tissue encasing the mesh was 3-
to 4-mm thick, uniform, and grossly and microscopi-
cally identical to that seen in the noninfected dogs.
The monofilament structure of the polypropylene pre-
vents bacteria from being trapped by the fibers of the
mesh. This makes polypropylene mesh less likely than
other synthetic meshes (e.g., Teflon) to become in-
fected in the presence of bacteria.2
The majority (14 [67%] of 21 cases) of cases re-
quiring polypropylene mesh implantation in this study
were animals which presented for thoracic wall
masses. In defects involving the caudal thoracic wall
from the ninth to 13th rib, the diaphragm can be
dissected from the thoracic wall, transposed cranial
to the defect, and sutured to the intercostal muscles. 20
However, this may require the resection of the caudal
lung lobe. Also, in the authors’ experience, the cos-
metic result is better when mesh is used. In both the
human and veterinary literature, polypropylene mesh
has been used successfully in the closure of these
defects. 4–7,21,22
May/June 1998, Vol. 34
Only one case in this study developed a postopera-
tive infection which resolved with thoracic drainage
and antibiotics. It is not clear if the infection was due
to the mesh or was secondary to surgical contamina-
tion. The dog has been followed for two years postop-
eratively and has had no further problems associated
with his implant. The low incidence of infection may
be due to the use of prophylactic antibiotics. However,
implant-related infection did not develop in the four
cases that did not receive antibiotics prophylactically.
Several of the cases had undergone previous surgi-
cal procedures at the site of mesh implantation, a
factor that could predispose to wound complications
like infection. One case (with a chronic ventral
incisional hernia) had mesh implanted into a Pseudomo-
nas-contaminated wound without developing a post-
operative wound infection or any long-term problems.
The very low incidence of implant-related sepsis con-
firms previous observations of polypropylene mesh
being well tolerated by tissues and not supporting
bacterial growth or sequestration when compared to
other mesh materials. 2 Although implantation of any
nonabsorbable implant into an obviously infected area
is not recommended, the surgeon may not have any
choice when reconstruction is necessary.
Immediate postoperative complications occurred
in 50% of the cases in this study. This complication
rate is much higher than that previously reported by
Matthiesen, et al. 6 Their study evaluated thoracic wall
resections and reported no incisional complications
in the 14 animals implanted with polypropylene
(Marlex) mesh in the first five days after surgery. The
difference in complication rate between their study
and this study may involve the use of drains. It is not
noted in that study whether drains were placed at the
surgery sites. Penrose drains were placed in four cases
in this study. None of the cases which had Penrose
drains placed intraoperatively developed seromas. In
eight (50%) of the 16 cases in which drains were not
placed, seromas developed. Defect size did not corre-
late with seroma formation. Except in the cases in
which the seroma was treated by drainage, the diag-
nosis of seroma was based only upon clinical evi-
dence of a fluctuant mass under the incision. Although
the presence of bacteria in these fluctuant masses
cannot be ruled out, it is unlikely that any of these
were abscesses since there was not clinical evidence
of infection and all resolved with conservative treat-
ment (i.e., warm compresses). Therefore, implanta-
tion of Penrose drains appeared to be an effective
prevention for seroma development. Placement of
Penrose drains may act as a route of bacterial con-
tamination in the surgical site. To prevent this com-
plication, drains always should be covered by a
bandage. All of the seromas resolved with conserva-
tive therapy consisting of warm compresses and band-
May/June 1998, Vol. 34
aging or placement of a Penrose drain at the site of
the seroma. The development of a seroma had no
effect on the long-term outcome.
The only reported long-term (six months or longer)
complication was mass recurrence at the original re-
section site in seven (50%) of 14 cases. Five of the
recurrences were at the site of thoracic wall mass
removal. The average number of ribs resected in these
cases was 1.8. The average number of ribs resected in
the other four cases without recurrence was 3.5. Al-
though the number of cases is low and histopathology
of the recurrent mass was available only in one of
five cases, wide excision of a malignant thoracic wall
mass should entail removal of more than one or two
ribs. Otherwise, regrowth at the primary tumor site
appears likely. No difference in recurrence of ab-
dominal wall masses was detected as being related to
the size of the area resected.
The median survival time for those cases with neo-
plasia and long-term follow-up was 14 months (range,
one to 93 months). Although the number of cases is
small in each group, the mean survival time (the mean
is used rather than the median because of the small
sample size) for each tumor type is 14 months for
osteosarcoma (only one case followed long-term),
11.8 months for chondrosarcoma (n=4), and 11
months for fibrosarcoma (n=2). These results are simi-
lar to those reported previously except for the
osteosarcoma case which lived longer than the previ-
ously reported median survival time of 3.3 months.6
Biopsy results were available on two of the three
cases in which a second resection was performed.
One biopsy included the original mesh implant and
chondrosarcoma was diagnosed on histopathology.
The second biopsy did not include the original mesh,
and intralesional foreign material and fibrosis of the
abdominal wall were described on histopathology.
Histopathology performed up to six months after im-
plantation of polypropylene mesh in experimental ani-
mals shows that the mesh is infiltrated uniformly by
fibrous tissue with a minimal foreign body reaction
and is not broken down by the body. 2 The foreign
material identified in the biopsy is most likely suture
material placed in order to close dead space subse-
quent to mass removal. Fibrosis of a body wall occurs
subsequent to any surgical procedure and would be
expected following en bloc resection of a body wall
tumor.
Conclusion
Polypropylene mesh appears to be a satisfactory im-
plant for dogs and cats with large body wall defects.
Seromas were common, immediate, postoperative
complications which had no effect on long-term out-
come. Placement of Penrose drains at the surgery
sites intraoperatively prevented the occurrence of this
Polypropylene Mesh 233
complication. None of the implants had to be re-
moved because of acute or chronic infection. Malig-
nant body wall neoplasms were less likely to recur if
wide excision was performed. Multiple rib excision
(of three to four ribs) resulted in reduced recurrence
rate in animals with thoracic wall tumors.
a
Marlex mesh; Davol, Cranston, RI
b
Prolene mesh; Ethicon, Somerville, NJ
c
Prolene suture; Ethicon, Somerville, NJ
d
PDS; Ethicon, Somerville, NJ
e
Noroxin; Merck & Co., West Point, PA
f
Kefzol; Eli Lilly & Co., Indianapolis, IN
g
CefaTabs; Fort Dodge Laboratories, Fort Dodge, IA
References
1. Geisler F, Gotlieb A, Fried D. Agenesis of the right diaphragm repaired
with Marlex. J Ped Surg 1979;12:587–90.
2. Usher FC, Gannon JP. Marlex mesh, a new plastic mesh for replacing
tissue defects. Am Med Assoc Arch Surg 1959;78:131–7.
3. Usher FC, Wallace SA. Tissue reaction to plastics. Am Med Assoc Arch
Surg 1958;76:997–9.
4. Bright RM. Reconstruction of thoracic wall defects using Marlex mesh.
J Am Anim Hosp Assoc 1981;17:415–20.
5. Fox SM, Bright RM, Hammond DL. Reconstruction of tissue deficits
with Marlex mesh. Comp Cont Ed Pract Vet 1988;8:897–904.
6. Matthiesen DT, Clark GN, Orsher RJ, Pardo AO, Glennon J, Patnaik AK.
En bloc resection of primary rib tumors in 40 dogs. Vet Surg 1992;21:
201–4.
7. Brasmer TH. Thoracic wall reconstruction in dogs. J Am Vet Med Assoc
1971;159:1758–62.
8. Furneaux RW. Tracheal reconstruction with knitted polypropylene mesh
in a dachshund dog. J Sm Anim Pract 1973;14:619–24.
9. Blades B, Paul JS. Chest wall tumors. Ann Surg 1950;131:976–84.
10. Shah JP, Urban JA. Full thickness chest wall resection from recurrent
breast carcinoma involving the bony chest wall. Cancer 1975;35:
567–73.
11. Parrish FF, Murray JA, Urquhart BA. The use of polyethylene mesh
(Marlex) as an adjunct in reconstructive surgery of the extremities.
Clin Orth Rel Res 1978;137:276–86.
12. Scales JT. Discussion on metals and synthetic materials in relation to
tissues. Tissue reactions to synthetic materials. Proc R Soc Med
1953;46:647–52.
13. Jenkins SD, Klamer TW, Parteka JJ, Condon RE. A comparison of
prosthetic materials used to repair abdominal wall defects. Surg
1983;94:392–8.
14. Bleichrodt RP, Simmermacher RKJ, van der Lei B, Schakenraad JM.
Expanded polytetrafluoroethylene patch versus polypropylene mesh for
the repair of contaminated defects of the abdominal wall. Surg Gynecol
Obstet 1993;176:18–24.
15. Usher FC, Fries JG, Ochsner JL, Tuttle LLD. Marlex mesh, a new plastic
mesh for replacing tissue defects. Am Med Assoc Arch Surg 1959;
78:138–45.
16. Jones RV, Boeke PJ. Properties of Marlex 50 ethylene polymer.
Ind Eng Chem 1956;48:1155–61.
17. Pourdeyhimi B. Porosity of surgical mesh fabrics: new technology.
J Biomed Mater Res 1989;23:145–52.
18. Chvapil M, Holusa R, Kliment K, et al. Some chemical and biological
characteristics of a new collagen-polymer compound material.
J Biomed Mater Res 1969;3:315–22.
19. Taylor DF, Smith FB. Porous methyl methacrylate as an implant mate-
rial. J Biomed Mater Res 1972;6:467–75.
20. Aronsohn M. Diaphragmatic advancement for defects of the caudal
thoracic wall in the dog. Vet Surg 1984;13:26–8.
21. Kroll SS, Walsh G, Ryan B, King R. Risks and benefits of using Marlex
mesh in chest wall reconstruction. Ann Plas Surg 1993;31:303–6.
22. Graham J, Usher FC, Perry JL, Barkley HT. Marlex mesh as a prosthesis
in the repair of thoracic wall defects. Ann Surg 1960;151:469–79.
The sedative and cardiorespiratory effects of an intramuscular injection of diazepam
(3 mg/kg body weight), acepromazine (0.1 mg/kg body weight), or xylazine (2 mg/kg
body weight) in ferrets (n=10, crossover design) was evaluated. Time from injection
to assuming lateral recumbency was not significantly different between the three
drugs. Duration of recumbency expressed as mean±standard deviation was
significantly longer with xylazine (68.3±20.8 min) than with diazepam (43.2±8.2 min)
or acepromazine (49.8±11.2 min). Sedation was graded to be the best in the
xylazine-treated ferrets and worst in the diazepam-treated ferrets. Analgesia was
judged only to be present following xylazine injection. Systolic blood pressure,
oxyhemoglobin saturation, and end-expired carbon dioxide (CO2) were similar with
all three drugs. It was concluded that, at the doses administered, xylazine provided
better chemical restraint in the healthy ferret than either acepromazine or diazepam.
J Am Anim Hosp Assoc 1998;34:234–41.

Jeff C. H. Ko, DVM, MS, Introduction

Diplomate ACVA
Constance F. Nicklin, MS
Terrell G. Heaton-Jones, DVM
Wei-Chen Kuo, DVM
O procedures. Diazepam, acepromazine, and xylazine are used com-
Domestic ferrets (Mustela putorius furo) are becoming increasingly
popular as household pets. There are an estimated eight-to-12 million
ferrets in the United States.1 The domestic ferret can be kept legally
as a pet in 47 states. 2 Veterinary care of ferrets ranges from nonin-
vasive procedures such as complete physical examinations, nail trim-
ming, ear cleaning, diagnostic whole body radiography, and dental
prophylaxis, to invasive procedures such as blood sampling and sur-
gery. Sedation, immobilization, or both is required usually for such
monly as tranquilizers/sedatives in dogs and cats. 3 These drugs have
been used to sedate ferrets for various types of procedures. 2–4 How-
ever, there are no reports in the literature of controlled studies evalu-
ating the sedative or cardiorespiratory effects of these drugs in ferrets.
The purposes of this study were to evaluate and compare the sedative
and cardiorespiratory effects of commonly recommended doses of
diazepam, acepromazine, and xylazine in the domestic ferret.

Materials and Methods

This project was approved by the Animal Care and Use Committee of
the University of Florida.

From the Anesthesiology Section,
Department of Large Animal
Clinical Sciences,
College of Veterinary Medicine,
University of Florida,
Gainesville, Florida 32610-0136.
Animals
Ten, healthy, one-year-old, intact male ferrets weighing between 1.55
kg and 2.05 kg were studied. The ferrets were obtained from a com-
mercial vendor and housed individually in the University of Florida’s
laboratory animal care and use certified facility. The ferrets were fed
a commercial food and provided water ad libitum. Each ferret was
judged to be healthy based on complete blood counts (CBCs), blood
chemistries, and physical examinations. All vaccinations and

234 JOURNAL of the American Animal Hospital Association

pam a [3 mg/kg body weight], acepromazineb [0.1 mg/kg
body weight], and xylazine c [2 mg/kg body weight])
administration. Each ferret received the three indi-
vidual sedatives. Each animal was allowed seven
days’ rest between each sedative. For acepromazine
and xylazine, a single intramuscular (IM) injection
was made in the semitendinosus/semimembranosus
muscle. Due to the large drug volume (approximately
1 ml) of diazepam, the dose was divided equally into
two parts and injected in each hind limb.
The IM dose was based on a dose extrapolation
from the dog and cat, the authors’ previous clinical
experience, and preliminary studies in the ferret. Dur-
ing the preliminary studies, ferrets received acepro-
mazine ranging from 0.05 to 0.3 mg/kg body weight.
Ferrets that received acepromazine at a dose of 0.05
mg/kg body weight IM did not become sedate, while
one ferret that received 0.3 mg/kg body weight IM
had a prolonged recovery (of more than 120 min) and
became hypothermic. Similar effects were induced
following low and high IM doses of diazepam (2 mg/kg
body weight and 4 mg/kg body weight, respectively)
and xylazine (1 mg/kg body weight and 4 mg/kg body
weight, respectively).
Monitoring
Baseline (time zero) heart rate (HR), electrocardio-
gram (EKG), indirect systolic blood pressure (SBP),
hemoglobin oxygen saturation (SpO 2), respiratory rate
(RR), exhaled carbon dioxide (CO 2), and rectal tem-
perature were recorded during each trial prior to the
drug injection. 7 Except for the rectal temperature, all
readings were measured three consecutive times, and
values were averaged to obtain the recording. Mea-
surements were recorded at time zero, five, 10, 15,
20, 30, 40, 50, 60, 70, 80, 90, and 100 minutes after
drug administration or until the ferret became mobile.
Analgesia, palpebral and corneal reflexes, and degree
of muscle relaxation also were assessed at each time
interval during each trial.
Detailed description of the cardiorespiratory moni-
toring has been reported previously 7 and is mentioned
briefly here. Heart rate and EKG measurements d were
recorded using lead II attached to surface electrodes. e
The hair was clipped; the pregelled, disposable, sur-
face-adhesive electrodes were attached; the EKG
leads were connected; and the EKG was monitored
continuously from 10 minutes preinjection until the
racy had been checked prior to the trial by use of a
mercury manometer, h was connected to the pressure
cuff. A Doppler flow transducer i was taped caudal to
the blood pressure cuff along the ventral surface of
the tail to obtain a clear caudal arterial flow signal
from the Doppler ultrasound unit.
The pulse and SpO2 were monitored continuously
with a pulse oximeter j placed on the tail. The hair on
the tail was clipped and cleaned, and a clip-on type
pulse oximetry probe was placed near the tip. Chest
excursion was used to measure the RR. If the animal
was tachypneic with shallow breaths, chest excur-
sions became difficult to count and mainstream
capnography with infrared sensor k was used for RR
determination. The RR was recorded three times, and
values were averaged to obtain the measurement. The
capnography sensor was held directly on the nose of
the ferret to detect exhaled CO 2.
Rectal temperature was monitored continuously
during each trial using an electronic rectal thermom-
eter connected with a thermoconduction cable.l Rec-
tal temperature was maintained between 38˚ and 39.5˚
C by placing the ferret under a heat lamp. Palpebral
and corneal reflexes were assessed with a 22-gauge,
over-the-needle intravenous (IV) catheterm without
the metal stylet. The catheter was used to touch gen-
tly the eyelid and medial canthus of the eye to elicit a
palpebral and corneal reflex, respectively. Reflexes
were recorded as present or absent.
A padded hemostat, to prevent tissue damage, was
used to assess analgesia by applying pressure to the
toe web of the left front limb and abdominal skin.
Limb withdrawal or gross, purposeful movements as-
sociated with toe and abdominal skin pinches were
considered positive pain responses. Response to tail
clamping was evaluated with a 2-cm Backhaus towel
clamp. The hair on the ferret’s tail was clipped, and
pressure was applied around the tail where the di-
ameter was approximately the same as the jaw di-
ameter. A reproducible force was made at the same
site by squeezing the towel clamp jaws and stops
together; locking the third rachet tooth and thereby
creating a blunt, noxious stimulus; and leaving the
clamp in place for 30 seconds or until the ferret
responded (i.e., with vocalization or any gross,
purposeful movements). Response to painful stimuli
was assessed after all physiological parameters
were recorded.
 Mild signs of excitement, continuous movement, numerous attempts to rise, poor muscle relaxation 2
Hyperkinesis, obvious signs of excitement, does not become recumbent or assumes recumbency briefly, 1
poor muscular relaxation

Recovery Characteristics Score

Assumes sternal recumbency with little or no struggling, stands and walks with little or no difficulty 3
Some struggling, requires assistance to stand, very responsive to external stimuli, and becomes quiet 2
in sternal recumbency
Unable to assume sternal recumbency, becomes hyperkinetic when assisted, paddling and swimming motion 1

Table 1
Sedative-Analgesic Effects* in Ferrets

Values Diazepam Acepromazine Xylazine

Injection to lateral recumbency (min) 3.9±1.4a 5.7±3.7a 2.5±0.9a
Duration of dorsal recumbency (min) 43.2±8.2a 49.8±11.2a 68.3±20.8b
Injection to complete mobilization (min) 51.3±12.8a 56.7±11.9a 71.3±19.1b
Dorsal recumbency to sternal recumbency (min) 1.2±1.3a 1.5±1.6a 0.7±1.6a
Sternal recumbency to standing/mobilization (min) 2.6±1.6a 2.0±1.5a 0.8 ±1.2a
Toe pinch analgesia (min) nonea nonea 40.5±27.3b
Skin pinch analgesia (min) nonea nonea 32.5±18.1b
Tail clamp analgesia (min) nonea nonea 35.8±17.4b
Duration of intubation (min) nonea nonea nonea
Loss of corneal reflex (min) 0.8±2.0a nonea 1.7±4.9a
Loss of palpebral reflex (min) 1.7±2.9a 4.2±6.6a 13.3±23.4a
Quality of sedation 2.2±0.9a 2.6±0.7b 3.0±0.0b
Quality of recovery 3.0±0.0a 3.0±0.0a 3.0±0.0a
Body weight (kg) 1.6±0.1a 1.7±0.1a 1.8±0.1a

* Ferrets (n=10) treated with intramuscular diazepam (3 mg/kg body weight), acepromazine (0.1 mg/kg body weight),
or xylazine (2 mg/kg body weight); all values are presented as mean±standard deviation (rows of mean values with
different alphabetic superscripts indicate a significant difference [p less than 0.05] from other treatments; rows of
mean values with same alphabetic superscripts indicate no significant difference from other treatments)

Muscle relaxation was assessed subjectively using
hind-limb extensor rigidity and jaw tone resistance.
The ease of endotracheal intubation was evaluated 10
minutes following IM injection. Endotracheal intuba-
tion was attempted using a 2- to 3-mm internal diameter,
cuffed, oral-nasal-tracheal tube and a laryngoscope
with #1 Miller blade. If the ferret had excessive jaw
tone or exhibited coughing, swallowing, or gagging
during attempted intubation, the process was aborted
and attempted five minutes later. The scoring systems
used to assess the quality of sedation and recovery are
described in the Appendix.
All data is presented as mean±standard deviation
(SD). Analysis of variance (ANOVA) was used to
compare observations and results among the three
treatments [Table 1]. Kruskal-Wallis one-way ANOVA,
a nonparametric test, was used to compare the seda-
tive and recovery scores. Two-way ANOVA was used
to test for significant differences in HR, SBP, SpO 2,
RR, and exhaled CO2 within and among treatment
All three sedatives induced lateral recumbency [Table
1]. All but one ferret assumed lateral recumbency at
approximately six minutes. One acepromazine-treated
ferret did not become recumbent for 13 minutes. On-
set of drug-induced sedation was graded as smooth in
the xylazine and acepromazine groups but was mod-
erate-to-poor in the diazepam-treated ferrets. Diaz-
epam response was characterized by excitement,
restlessness, pacing from side-to-side, anxiousness,
and sensitivity to noise.
Quality of sedation was best following xylazine
[Table 1]. Xylazine-treated ferrets were placed easily
in dorsal recumbency in a trough. They did not react
to any of the instrumentation (i.e., blood pressure
cuff, pulse oximeter probe, and rectal thermometer)
or manipulation. In contrast, diazepam-treated ferrets
objected to being placed in dorsal recumbency and
exhibited excitement characterized by front-limb pad-
dling, agitation, restlessness, and resistance to the
instrumentation. All diazepam-treated ferrets were
responsive to noise. Only one of the acepromazine-
treated ferrets and none of the xylazine-treated fer-
rets were noise responsive.
Endotracheal intubation could not be achieved with
any drug. The ferrets either had tight jaw tone or
displayed chewing motions and tongue flicking when
intubation was attempted. Analgesia was observed
only in the xylazine-treated ferrets [Table 1]. Hind-limb
muscle relaxation was excellent in the xylazine-
treated ferrets but moderate or poor in the diazepam-
and acepromazine-treated ferrets. Chemical restraint
was good enough in the xylazine-treated ferrets to
allow nail clipping and ear cleaning 30 minutes after
drug administration. Nail clipping was difficult and
ear cleaning was impossible following diazepam ad-
ministration; ferrets frequently responded to these
procedures by shaking their heads and paws and by
picking up their heads and attempting to rise. Using
the scaling system [see Appendix], recovery was
graded as smooth in all three treatment groups [Table 1].
Heart rate and SBP data is presented in Table 2.
Heart rate did not change significantly over time fol-
lowing diazepam or acepromazine administration but
significantly decreased from baseline value after
xylazine administration and remained so until the end
of the recording period. Mean baseline HR values
were not significantly different among treatment
groups. Heart rate was never significantly different
between the diazepam- and acepromazine-treated fer-
arrhythmia, and occasional sinus arrest were observed
in all three treatment groups.
Hemoglobin oxygen saturation, RR, and exhaled
CO2 values are presented in Table 3. All three drugs
reduced oxygen saturation values. Significant de-
creases in RR were recorded at five and 50 minutes in
the xylazine- and acepromazine-treated ferrets, re-
spectively. The RR in the xylazine-treated ferrets re-
mained decreased for the duration of the experiment.
Significant decreases in RR were not observed after
diazepam administration. Significant differences in
RR were not observed between the diazepam and
xylazine or acepromazine and xylazine treatments.
Exhaled CO 2 values significantly increased 15 min-
utes following diazepam injection and remained so
for 50 minutes. Time from injection to complete re-
covery was significantly longer with xylazine [Table 1].
Discussion
This study compared the sedative action of three com-
monly used drugs in ferrets. All three tranquilizers
produced sedation and lateral recumbency within six
minutes of drug administration. The transition from
injection to lateral recumbency in the diazepam-
treated ferret was moderate-to-poor; restlessness and
excitement were observed. It has been reported that
benzodiazepines (e.g., diazepam, midazolam) can in-
duce restlessness and excitement in some dogs and
cats. 3,8 It is possible that a similar reaction can occur
in ferrets. Secondly, the relatively large injection vol-
ume required at the dose of diazepam used in this
study may be of concern. Although no permanent
injury was observed, lameness was observed in three
ferrets for two-to-three hours after recovery. Ferrets
receiving acepromazine or xylazine showed no signs
of excitement following injection, and the onset of
sedation was graded as smooth with both of these
drugs.
The quality of sedation was poorest following di-
azepam. Diazepam-treated ferrets responded to the
noise produced by the pulse oximeter and Doppler by
either picking up their heads, paddling, or attempting
to roll over. Poor sedation was evidenced further by
the difficulties encountered during the nail clipping
and ear cleaning procedures. When compared to
xylazine-treated ferrets, acepromazine-treated ferrets
tolerated nail clipping and ear cleaning procedures
less, but the procedures clearly were easier to per-
form on the acepromazine-treated ferrets than on the
 Table 2
Effects of Diazepam, Acepromazine, and Xylazine* on Cardiovascular Functions in Ferrets

Group Diazepam Acepromazine Xylazin

Time Heart Rate Systolic Blood Pressure Heart Rate Systolic Blood Pressure Heart Rate Systol
(min) (beats/min) (mmHg) (beats/min) (mmHg) (beats/min)
0 236.3±14.11 (10)† 162.0±14.9 a (10) 233.0±24.6 1 (10) 151.3±10.3a (10) 224.2±23.0a,1 (10)
5 225.8±29.6 1 (10) 135.0±16.8 b (10) 220.0±26.2 1 (10) 116.2±7.9b (10) 164.8±23.7b,2 (10)
10 225.7±24.8 1 (10) 137.3±14.7b,1 (10) 239.5±30.5 1 (10) 108.7±19.8b,2 (10) 156.5±25.9b,2 (10)
15 209.0±11.1 1 (10) 123.7±19.5 b (10) 214.3±24.3 1 (10) 108.3±12.1b (10) 148.3±22.0b,2 (10)
20 219.7±26.1 1 (10) 118.7±9.7b (10) 229.2±39.5 1 (10) 104.8±14.1b (10) 143.5±21.7b,2 (10)
30 206.3±20.2 1 (10) 114.0±12.1 b (10) 220.2±27.9 1 (10) 99.0±14.2b (10) 143.7±16.2b,2 (10)
40 225.8±18.7 1 (8) 112.0±10.6 b (8) 230.0±33.1 1 (10) 101.8±19.6b (10) 135.7±14.1b,2 (10)
50 244.3±22.2 1 (6) 112.0±18.3 b (6) 241.0±48.3 1 (6) 98.5±25.9b (6) 135.8±17.7b,2 (10)
60 227.0±21.8 1 (3) 120.0±11.3 b (3) 269.3±19.1 1 (5) 95.3±15.1b (5) 127.5±13.2b,2 (10)
70 209.2 (1) 152.0 (1) 255.0 (1) 106.0 (1) 134.3±11.9b (10)
80 — — 265.0 (1) 110.0 (1) 129.5±5.0b (10)
90 — — 284.0 (1) 106.0 (1) 124.8±14.5b (6)
100 — — 225.0 (1) 110.0 (1) 127.0±9.6b (6)

* Heart rate and systolic blood pressure of ferrets (n=10) sedated with diazepam (3 mg/kg body weight), acepromazine (0.1 mg/kg body weight),
(2 mg/kg body weight); all values are presented as mean±standard deviation (columns of mean values with different alphabetic superscripts indi
difference [p less than 0.05] from baseline value within a treatment; columns of mean values without alphabetic superscripts indicate no signific
the baseline values within a treatment; rows of mean values with different numerical superscripts indicate a significant difference [p less than 0.
treatments; rows of mean values with the same numerical superscripts indicate no significant difference from other treatments)
†
Numbers in parentheses indicate the number of ferrets in recumbency
 Table 3
Effects of Diazepam, Acepromazine, and Xylazine* on Respiratory Functions in Ferrets

Group Diazepam Acepromazine Xylazine

Respiratory Exhaled Respiratory Exhaled Respiratory
Time SpO2 † Rate CO2‡ SpO2 Rate CO2 SpO2 Rate
(min) (%) (breaths/min) (mmHg) (%) (breaths/min) (mmHg) (%) (breaths/min)
0 92.0±1.9a (10) 38.7±18.2 (10)§ 50.3±4.4a (10) 94.4±1.5 (10) 42.0±15.3a (10) 51.8±3.6 (10) 92.8±2.3 (10) 57.3±14.8a (10
5 83.3±5.3b (10) 45.7±19.6 (10) 53.8±5.6a (10) 87.8±5.3 (10) 40.0±8.9a (10) 53.5±3.4 (10) 82.0±7.5 (10) 39.3±6.7b (10)
10 85.0±5.4b (10) 24.7±8.91 (10) 55.7±2.4a (10) 88.2±6.7 (10) 38.3±4.8b,2 (10) 54.2±3.0 (10) 86.8±6.8 (10) 32.8±7.0b,1,2 (1
15 83.8±6.1b (10) 27.8±10.9 (10) 58.0±3.0b (10) 90.5±2.7 (10) 34.8±8.3b (10) 54.0±4.0 (10) 85.0±8.4 (10) 35.8±8.6b (10)
20 87.5±4.2b (10) 27.0±6.3 (10) 57.3±2.9b (10) 87.3±4.3 (10) 29.7±7.3b (10) 54.7±4.1 (10) 89.0±5.3 (10) 36.0±6.0b (10)
b
30 90.3±3.1 (10) 25.7±5.9 (10) 57.7±4.2b (10) 86.5±6.4 (10) 26.5±2.2b (10) 56.7±5.2 (10) 89.3±5.2 (10) 32.8±6.5b (10)
40 88.4±3.6b (8) 38.2±16.6 (8) 56.3±3.8b (8) 90.5±4.3 (10) 33.0±6.3b (10) 53.7±6.5 (10) 89.2±4.4 (10) 33.2±8.1b (10)
50 93.7±1.5a (6) 20.3±7.8 (6) 58.0±4.4b (6) 89.0±2.9 (6) 20.3±5.9b (6) 55.0±1.8 (6) 89.0±2.9 (6) 30.2±8.3b (10)
60 90.0±2.8a,b (6) 35.0±15.6 (3) 56.0±3.2b (3) 86.0±4.6 (5) 37.3±15.4b (5) 51.7±8.7 (5) 91.0±3.1 (10) 28.5±7.2b (10)
70 92.0 (1) 78.0 (1) 52.0 (1) 84.0 (1) 23.0 (1) 59.0 (1) 87.7±6.9 (10) 29.3±6.1b (10)
80 — — — 84.0 (1) 26.0 (1) 59.0 (1) 88.7±6.3 (10) 31.2±8.1b (10)
90 — — — 86.0 (1) 15.0 (1) 59.0 (1) 88.6±4.3 (6) 30.3±2.4b (6)
100 — — — 86.0 (1) 28.0 (1) 49.0 (1) 89.4±4.0 (6) 31.3±4.8b (6)

* Oxyhemoglobin saturations (SpO2), respiratory rates, and exhaled carbon dioxide (CO2) concentrations of ferrets sedated with diazepam (3 mg/kg body weight), a
mg/kg body weight), or xylazine (2 mg/kg body weight); all values are presented as mean±standard deviation (columns of mean values with different alphabetic s
significant difference [p less than 0.05] from baseline value within a treatment; columns of mean values without alphabetic superscripts indicate no significant dif
baseline values within a treatment; rows of mean values with different numerical superscripts indicate a significant difference [p less than 0.05] from other treatm
values without numerical superscripts indicate no significant difference from other treatments)
†
SpO2=hemoglobin oxygen saturation
‡
CO2=carbon dioxide
§
Numbers in parentheses indicate the number of ferrets in recumbency

tail pinches was present only after xylazine injection.
This was expected, since only xylazine possessed an-
algesic actions. 3
Reportedly, acepromazine given alone as a pre-
anesthetic in the ferret can cause prolonged recov-
ery.6 With the dosages used in this study, the duration
from injection to complete mobilization was signifi-
cantly longer in the xylazine-treated ferrets (71.3±19.1
min) when compared to the diazepam- (51.3±12.8
min) or acepromazine- (56.7±11.9 min) treated fer-
rets. The significantly longer duration in the xylazine
group was associated with a longer duration of dorsal
recumbency [Table 1].
In a previous study, ferrets given tiletamine-
zolazepam often sneezed during the sedative period.7
In this study, sneezing was not observed. Further-
more, vomiting or regurgitation did not occur follow-
ing any drug administration.
Heart rate did not change from baseline values
following either diazepam or acepromazine adminis-
tration, but HR decreased following xylazine injec-
tion. Throughout the recording period, HR was lower
in the xylazine-treated ferrets than it was in either the
diazepam- or acepromazine-treated ferrets. The de-
crease in HR likely was due to decreased sympathetic
activity and enhanced vagal effects caused by
xylazine.9 Sinus arrhythmia is a normal finding and is
observed commonly in dogs10 but not in cats.11 It
represents alternating periods of slower and more
rapid heart rates, usually related to respiration and
caused by changing levels of vagal tone. 10 Heart rate
typically increases with inspiration and decreases with
expiration.10 In this study, sinus arrhythmia was ob-
served commonly prior to drug administration. The
sinus arrhythmia appeared to correspond with the res-
piratory cycle, similar to that observed in dogs. Fur-
thermore and somewhat surprisingly, profound sinus
arrhythmia accompanied by second-degree AV heart
block, an occasional sinus arrest, or both were ob-
served in all the ferrets regardless of the drug treatment.
It is well known that acepromazine and xylazine
have the potential to induce hypotension in dogs and
cats. 3 Despite a decrease in SBP in all three treatment
groups in this study, blood pressure was maintained
well throughout the recording period. The lowest
mean SBP was 94.0±12.1 mmHg in the xylazine-
treated ferrets at 100 minutes after injection. Although
a definitive hypotensive value has yet to be deter-
mined in the anesthetized ferret, SBP lower than 80 to
2
in the anesthetized animal. 12,13 The lowest recorded
SpO 2 in this study was 82.0±7.5% five minutes fol-
lowing xylazine administration. It should be under-
stood that when compared to arterial hemoglobin
saturation, pulse oximeters, when used on extremely
small vessels, often underestimate SpO 2. Considering
this, together with clinical signs (i.e., pink mucosal
membranes and normal recoveries), these sedatives at
the dosages assessed in this study did not appear to
induce serious hypoxemia in ferrets.
The mean RR significantly decreased from baseline
values in all three treatment groups. Despite this de-
crease, the exhaled CO2 values changed minimally
from the baseline value during the 100-minute re-
cording period. This is consistent with the finding
that these drugs generally are not considered potent
respiratory depressants unless administered in ex-
tremely high doses.3
Conclusion
The results of this study indicate that diazepam (3.0
mg/kg body weight), acepromazine (0.1 mg/kg body
weight), and xylazine (2.0 mg/kg body weight) can
induce some degree of sedation and lateral recum-
bency in the healthy ferret at the specific dosages
used. The duration of dorsal recumbency was signifi-
cantly longer with xylazine than with either diazepam
or acepromazine. Sedation was graded best with
xylazine and poorest with diazepam. Analgesia was
apparent only in xylazine-treated ferrets. Cardiac
arrhythmias (i.e., sinus arrhythmia, second-degree AV
heart block, and sinus arrest) were observed in all
three treatment groups. Hypotension, hypoxemia, and
hypercapnia were not significant concerns, and re-
covery was relatively short and smooth with all three
drugs. At the dosages given, xylazine appeared to be
the best tranquilizer/sedative for ferrets when
contemplating chemical restraint, minor painful pro-
cedures, or both. Diazepam alone cannot be recom-
mended for sedation because of its potential to induce
excitement and restlessness in this species and the
injection volume required.
a
Steris Laboratories, Inc., Phoenix, AZ
b
Fort Dodge Pharmaceuticals, Fort Dodge, IA
c
Miles, Inc., Shawnee Mission, KS
d
Passport; Datascope Corp., Paramus, NJ
e
Silver chloride ECG monitoring electrode; Medtek Southeast, Inc., St.
Petersburg, FL
 Angiocath; Becton-Dickinson, Sandy, UT
n 9. Antonaccio MJ, Robson RD, Kerwin L. Evidence for increased vagal
Statistix; 1992 edition, Analytical Software, St. Paul, MN
tone and enhancement of baroreceptor reflex activity after xylazine
(2(2,6-dimethylphenylamino)-4-H-5,6-dihydro1,3-thiazine) in anesthe-
Acknowledgments tized dogs. Eur J Pharmacol 1973;23:311–5.
10. Tilley LP. Analysis of common canine cardiac arrhythmias. In: Tilley
This project was supported by a grant from the Ameri- LP, ed. Essentials of canine and feline electrocardiography, interpreta-
can Animal Hospital Association. tion and treatment. 3rd ed. Philadelphia: Lea & Febiger Malvern,
1992:127–207.
11. Tilley LP. Analysis of common feline cardiac arrhythmias. In: Tilley LP,
ed. Essentials of canine and feline electrocardiography, interpretation
References and treatment. 3rd ed. Philadelphia: Lea & Febiger Malvern, 1992:208–52.
1. Morrisey JK. Accounting for the uniqueness of a fascinating creature. 12. Ko JCH. Noninvasive techniques in monitoring anesthetized patients.
Vet Med 1996;91(12):1082. Vet Tech 1996;17(5):301–8.
2. Gandolfi RC. The domestic ferret: a veterinary introduction. Calif Vet 13. LeBlanc PH, Sawyer DC. Electronic monitoring equipment. Semin Vet
1995;49(6):7–10. Med Surg (Sm Anim) 1993;8:119–26.
3. Thurmon JC, Tranquilli WJ, Benson GJ. Preanesthetics and anesthetic 14. Ko JCH, Harrison JM, Mladinich CHJ. Comparison of invasive and non-
adjuncts. In: Thurmon JC, Tranquilli WJ, Benson GJ, eds. Lumb & invasive cardiopulmonary techniques in ferrets. Abstract. Proceed, 21st
Jones’ veterinary anesthesia. 3rd ed. Baltimore: Williams & Wilkins, Ann Am Coll Vet Anesth, New Orleans, LA. 1996:45.
1996:183–209.
4. Ryland LM, Bernard SL, Gorham RJ. A clinical guide to the pet ferret.
Comp Cont Ed Pract Vet 1983;5:25–32.
 Evaluation of Sedative and
Cardiorespiratory Effects of Diazepam-
Butorphanol, Acepromazine-Butorphanol,
and Xylazine-Butorphanol in Ferrets
Ten ferrets were used in a crossover study to determine the sedative effects of
intramuscularly (IM) administered diazepam (3 mg/kg body weight)-butorphanol (0.2
mg/kg body weight), acepromazine (0.1 mg/kg body weight)-butorphanol (0.2 mg/kg
body weight), or xylazine (2.0 mg/kg body weight)-butorphanol (0.2 mg/kg body
weight). All ferrets became laterally recumbent following the administration of each
drug combination. The xylazine-butorphanol combination caused a significantly
longer (p less than 0.05) duration of analgesia than the diazepam-butorphanol and
acepromazine-butorphanol combinations. None of the ferrets could be intubated with
any of the drug combinations. The time from induction to recovery was significantly
shorter in the acepromazine-butorphanol-treated ferrets. A significantly lower heart
rate was observed in the xylazine-butorphanol-treated ferrets; however, an
acceptable systolic blood pressure was maintained. Ventilatory function was more
depressed in the diazepam-butorphanol- and xylazine-butorphanol-treated ferrets
than in the acepromazine-butorphanol-treated ferrets. Xylazine-butorphanol was
found to be the best combination for use in ferrets.
J Am Anim Hosp Assoc 1998;34:242–50.

Jeff C. H. Ko, DVM, MS, Introduction

Diplomate ACVA
Alexander Villarreal, BS
Wei-Chen Kuo, DVM
Constance F. Nicklin, MS
O ity of sedation and the cardiorespiratory side effects of various, in-
From the Anesthesiology Section,
Department of Large/Small Animal
Clinical Sciences,
College of Veterinary Medicine,
University of Florida,
Gainesville, Florida 32610-0136.
The domestic ferret (Mustela putorius furo) is becoming increasingly
popular as a household pet. In 47 states, it is legal to keep ferrets as
pets. 1 Veterinary care for ferrets ranges from noninvasive procedures
including complete physical examinations, nail clipping, ear clean-
ing, radiography, and dental prophylaxis, to invasive procedures in-
cluding blood sampling and surgery. Ferrets usually require sedation
or anesthesia for these procedures. A review of recent literature
indicates that there are few objective comparisons between the qual-
jectable, sedative drug combinations used in ferrets.
The anesthetic and cardiorespiratory effects of tiletamine-
zolazepam in combination with xylazine and ketamine,2 as well as
medetomidine in combination with butorphanol and ketamine 3 in the
ferret have been compared previously. In a recent comparative study,4
the authors found that diazepam (3 mg/kg body weight, intramuscu-
larly [IM]) induced an inadequate level of sedation for most
noninvasive procedures in the ferret. Acepromazine (0.1 mg/kg body
weight, IM) induced a reasonable level of tranquilization without
prolonged recovery. Xylazine (2 mg/kg body weight, IM) induced
reliable sedation and a short period of analgesia. Based on the results
of the quality of sedation, recovery, and the cardiorespiratory side
effects, xylazine was considered to be a better sedative than diazepam
or acepromazine in the ferret.4

242 JOURNAL of the American Animal Hospital Association

May/June 1998, Vol. 34 Combination Sedation in the Ferret 243

Appendix
Scoring Used for Quality of Sedation and Recovery

Sedation Characteristics Score

No outward sign of excitement, rapidly assumes lateral recumbency, and good muscular relaxation 3
Mild signs of excitement, continuous movement, numerous attempts to rise immediately after 2
assuming recumbency, poor muscle relaxation
Hyperkinesis, obvious signs of excitement, does not become recumbent or assumes recumbency briefly, 1
poor muscular relaxation

Sedative Recovery Characteristics Score

Assumes sternal recumbency with little or no struggling, attempts to stand and walk with little or no difficulty 3
Some struggling, requires assistance to stand, very responsive to external stimuli but becomes quiet 2
in sternal recumbency
Prolonged struggling, unable to assume sternal recumbency or difficulty in maintaining sternal or 1
standing position, becomes hyperkinetic when assisted, prolonged paddling and swimming motion

Butorphanol, an opioid agonist-antagonist with an-
algesic properties, administered to dogs (0.1 or 0.4
mg/kg body weight, intravenously) has been shown to
induce mild sedation and small decreases in heart rate
(HR), arterial oxygen tension, and arterial blood pres-
sure. 5 When butorphanol was combined with medeto-
midine in the ferret, analgesia was greater than when
medetomidine was used alone. 3 The authors’ previ-
ous results 4 showed that diazepam and acepromazine,
when used individually, induced unreliable sedation
and no analgesia. Therefore, it would be reasonable
to combine butorphanol with these tranquilizers to
enhance their sedative qualities and provide some
analgesia. The objective of the current study was to
compare the sedative and cardiorespiratory effects of
diazepam-butorphanol, acepromazine-butorphanol,
and xylazine-butorphanol in the ferret.
Materials and Methods
This project was approved by the Animal Care and
Use Committee of the University of Florida.
Animals
Ten, healthy, 1.5-year-old, intact male ferrets weigh-
ing from 1.5 to 1.9 kg were used. The ferrets were
obtained from a commercial vendor and housed indi-
vidually in a facility certified for laboratory animal
care and use. The ferrets were fed a commercial ferret
diet and allowed water ad libitum. The ferrets were
judged to be healthy based on complete blood counts,
blood chemistry profiles, and physical examinations.
Vaccinations and deworming were current. Food and
water were not withheld prior to sedation.
Experimental Design
In this randomized crossover study, each ferret served
as its own control. The drug combinations were diaz-
epam (3 mg/kg body weight)-butorphanol (0.2 mg/kg
body weight), acepromazine (0.1 mg/kg body weight)-
butorphanol (0.2 mg/kg body weight), and xylazine
(2 mg/kg body weight)-butorphanol (0.2 mg/kg body
weight). Treatments were separated by seven days.
The drugs were drawn separately and mixed in one
syringe immediately prior to administration. A single
IM injection was made in the semitendinosus/semi-
membranosus muscle. The dose of each drug was
based on a previous study in ferrets. 4
Evaluation of Sedation and Analgesia
The time from IM injection to lateral recumbency
was recorded. Immediately following lateral recum-
bency, each ferret was placed in dorsal recumbency
in a plastic trough. The righting reflex time was the
time required for the ferret to achieve sternal recum-
bency spontaneously from a dorsal recumbent posi-
tion. The time to recover from dorsal recumbency to
sternal recumbency and the time from sternal recum-
bency to complete mobilization were recorded. Com-
plete mobilization was defined as when the ferret
ambulated normally. The quality of sedation and re-
covery was graded subjectively according to the cat-
egories listed in the Appendix.
Muscle relaxation was assessed subjectively using
hind-limb extensor rigidity and jaw tone resistance
when tension was applied. Endotracheal intubation
was attempted five minutes after drug administration.
A 2-mm or 3-mm, internal diameter, cuffed endotra-
cheal tube and a laryngoscope with a #1 Miller blade
were used for intubation. If excessive jaw tone, cough-
ing, vigorous swallowing, or gagging occurred, the
procedure was aborted and attempted five minutes
later.
Palpebral and corneal reflexes were assessed using
a 22-gauge, over-the-needle intravenous catheter a
244 JOURNAL of the American Animal Hospital Association
without the metal stylet. The catheter was used to
touch gently the eyelid and the medial canthus of the
eye to elicit palpebral and corneal reflexes, respec-
tively. Reflexes were recorded as present or absent.
To assess analgesia, a padded hemostat was used to
apply pressure to the left front-limb toe web and to
the abdominal skin. Muscle twitching, limb with-
drawal, or gross, purposeful movements associated
with toe and abdominal skin pinches were considered
negative responses for analgesia. Tail analgesia was
evaluated with a 2-cm Backhaus towel clamp. The
hair on the ferret’s tail was clipped, and pressure was
applied around the tail where its diameter was ap-
proximately equal to the clamp’s jaw diameter. A
repeatable force was produced at the same site by
closing the Backhaus clamp to its third rachet, creat-
ing a “super maximal” stimulus. The clamp was left
in place for 30 seconds or until the ferret responded
(with vocalization or gross, purposeful movement or
both). Evaluation of analgesia was performed after all
physiological readings were recorded. All measure-
ments were recorded at zero (prior to the anesthetic
administration), five, 10, 15, 20, 30, 40, 50, 60, 70,
and 80 minutes following drug administration.
Evaluation of Cardiopulmonary Effects
The monitoring system used in this study was em-
ployed previously in another study to compare the
cardiopulmonary effects of injectable anesthetic com-
binations in ferrets.2,3 The pulse rate (PR), oxygen
hemoglobin saturation (SpO2 ), indirect systolic blood
pressure (SBP), electrocardiogram (EKG), rectal tem-
perature, respiratory rate (RR), and end-tidal carbon
dioxide (CO 2) were recorded prior to and after the
administration of each drug combination. All read-
ings, except the rectal temperature and the EKG, were
measured three consecutive times, and a mean value
was recorded.
Pulse rate and SpO 2 were monitored continuously
using a pulse oximeter.b The tail hair was clipped, the
skin was cleaned with alcohol, and a clip-on pulse
oximetry sensor was placed near the tail tip. Indirect
systolic blood pressure was measured using a neona-
tal blood pressure cuff c placed at the base of the tail
with the pneumatic bladder centered over the ventral
midline. A calibrated aneroid sphygmomanometerd
was connected to the pressure cuff. A Doppler flow
transducer e was taped along the ventral surface of the
tail, distal to the blood pressure cuff. Aqueous gel
was applied to the transducer probe to ensure ultra-
sonic coupling. Indirect SBP was measured by in-
creasing the pressure within the pneumatic cuff until
the flow signal disappeared, and then the cuff was
deflated slowly (at a rate of 1-to-2 mmHg per sec)
until a clear, consistent flow signal was heard. After
initial placement, indirect SBP was measured consis-
May/June 1998, Vol. 34
tently without readjustment of the cuff or the Doppler
transducer.
Each ferret was clipped on each side of the chest
and on the left side of the abdomen, cranial to the left
rear leg. The skin was cleaned with 70% alcohol prior
to attaching the pregelled, disposable, surface-adhe-
sive electrodes. f Electrocardiography was monitored
continuously for rate and rhythm using lead II,g be-
ginning 10 minutes prior to drug injection and until
the completion of each trial. The surface electrodes
appeared to cause minimal stress and maintained good
skin contact before, during, and after each trial. Sus-
pected EKG abnormalities were printed for later ex-
amination.
Each ferret was placed on a padded surgical table,
and rectal temperature was maintained between 36.8˚
to 38.5˚ C using a heat lamp. Core body temperature
was monitored continuously throughout each trial us-
ing an electronic thermometer connected to a thermo-
conduction cable.h Thoracic excursion was used to
measure the RR. To detect end-tidal CO 2 in the
nonintubated ferrets, a mainstream capnography with
an infrared sensor i was held directly on the nose until
the reading was obtained.
Statistical Analysis
All data is presented as a mean±standard deviation
(SD). The data was analyzed using analysis of vari-
ance (ANOVA) for repeated measures. If significant
(p of 0.05 or less) differences were detected, then
Tukey’s multiple comparison tests were used to de-
tect which treatment means were significantly different.
Results
Sedative and Analgesic Effects
All three sedative combinations induced lateral re-
cumbency within six minutes after IM injection [Table
1]. The acepromazine-butorphanol-treated ferrets took
longer to become laterally recumbent (p less than
0.05) than the other groups. The transition to lateral
recumbency was smooth in the xylazine-butorphanol-
treated ferrets. One diazepam-butorphanol-treated fer-
ret showed signs of hyperexcitement characterized by
pacing from side-to-side on the surgery table after
drug injection. The ferret did not become recumbent
for 12 minutes after drug injection. An acepromazine-
butorphanol-treated ferret did not become laterally
recumbent until nine minutes after drug injection.
One-third of the diazepam-butorphanol- and acepro-
mazine-butorphanol-treated ferrets resisted insertion
of the rectal temperature probe. They reacted by kick-
ing their hind limbs and attempting to rise from the
dorsally recumbent position. The temperature probe
was difficult to keep in place in these ferrets. None of
the xylazine-butorphanol-treated ferrets reacted to the
May/June 1998, Vol. 34 Combination Sedation in the Ferret 245

Table 1
Sedative and Recovery Effects* in Ferrets

Diazepam- Acepromazine- Xylazine-

Values Butorphanol Butorphanol Butorphanol
Injection to lateral recumbency (min) 3.4±2.2a,b 5.2±1.8a 2.1±0.6b
Duration of dorsal recumbency (min) 79.8±11.2a 65.7±17.5b 82.3±4.9a
Injection to complete mobilization (min) 85.8±12.6a 70.8±17.5b 86.7±9.0a
Dorsal recumbency to sternal recumbency (min) 0.9±1.0 1.0±2.7 0.6±1.6
Sternal recumbency to standing/mobilization (min) 5.1±4.2 3.7±9.6 3.1±4.8
Toe pinch analgesia (min) nonea 7.0±14.2a 54.5±11.2b
Skin pinch analgesia (min) nonea 2.5±5.4a 43.0±10.6b
Tail clamp analgesia (min) 4.0±9.7a 16.0±19.1a 69.5±5.0b
Duration of intubation (min) none none none
Loss of corneal reflex (min) 0.5±1.6 15.5±24.7 21.5±25.5
Loss of palpebral reflex (min) 8.5±14.5 40.5±26.1 53.5±16.0
Quality of sedation 2.5±0.8 2.8±0.4 3.0±0.0
Quality of recovery 2.9±0.3 2.8±0.6 3.0±0.0
Body weight (kg) 1.56±0.13 1.54±0.17 1.57±0.13

* Sedative effects of ferrets treated with intramuscular diazepam (3 mg/kg body weight)-butorphanol (0.2 mg/kg body
weight), acepromazine (0.1 mg/kg body weight)-butorphanol (0.2 mg/kg body weight), or xylazine (2 mg/kg body
weight)-butorphanol (0.2 mg/kg body weight) (all values are presented as mean±standard deviation; rows of mean
values with different alphabetic superscripts are significantly different; rows of mean values without superscripts are
not significantly different)

insertion of the temperature probe, and the probe
remained in place until the ferrets returned to sternal
recumbency. The diazepam-butorphanol- and acepro-
mazine-butorphanol-treated ferrets also responded to
the noise of the pulse oximeter and the Doppler dur-
ing the first 20-to-30 minutes after drug administra-
tion. None of the xylazine-butorphanol-treated ferrets
responded to the noise. Thirty minutes after diaz-
epam-butorphanol or acepromazine-butorphanol in-
jection, nail clipping and ear cleaning could be
achieved with only mild resistance. The same proce-
dures were completed in the xylazine-butorphanol-
treated ferrets without any resistance.
Endotracheal intubation was not possible at any
time in ferrets from the three treatment groups [Table
1]. Profuse salivation, sneezing, or vomiting was not
observed during the experiment. Analgesia was not
induced with the diazepam-butorphanol combination.
Analgesia was significantly shorter and more vari-
able in the acepromazine-butorphanol-treated ferrets
in comparison to the xylazine-butorphanol-treated fer-
rets [Table 1]. Hind-limb muscle relaxation was
judged to be excellent in the xylazine-butorphanol-
treated ferrets and mild-to-moderate in the diazepam-
butorphanol- and acepromazine-butorphanol-treated
ferrets. Loss of palpebral and corneal reflexes were
highly variable in all three groups [Table 1]. Myo-
clonic twitching of the limbs was observed occasion-
ally in the xylazine-butorphanol-treated ferrets but
not in the other groups. Recovery from dorsal to ster-
nal recumbency and from sternal recumbency to mo-
bility was smooth in all treatment groups [Table 1].
Three diazepam-butorphanol-treated ferrets devel-
oped hind-limb weakness after recovery. The lame-
ness had subsided 24 hours later.
Cardiorespiratory Effects
Pulse rate did not change significantly from the
baseline following diazepam-butorphanol and acepro-
mazine-butorphanol administration, but it decreased
significantly from the baseline following xylazine-
butorphanol administration. The lowest PR was
116.2±13.6 beats per minute recorded at 50 minutes
in the xylazine-butorphanol-treated ferrets [Table 2].
Mean PR was significantly lower in the xylazine-
butorphanol-treated ferrets than in the diazepam-
butorphanol- and acepromazine-butorphanol-treated
ferrets from five-to-80 minutes following drug injec-
tion [Table 2]. The SpO2 did not change significantly
from baseline values in the diazepam-butorphanol-
treated ferrets, but it was significantly lower than
baseline for the acepromazine-butorphanol-treated
ferrets 15 minutes after injection (97.5±0.8% versus
94.3±3.0%) [Table 3]. The xylazine-butorphanol-
treated ferrets had significantly lower SpO2 percentages
than the other groups between five and 30 minutes
 246

Table 2
Effects of Anesthetics* on Cardiovascular Functions in Ferrets

Group Diazepam-Butorphanol Acepromazine-Butorphanol Xylazine-Butorphanol

Time Pulse Rate Systolic Blood Pressure Pulse Rate Systolic Blood Pressure Pulse Rate Systolic Blood Pressure
(min) (beats/min) (mmHg) (beats/min) (mmHg) (beats/min) (mmHg)
0 235.8±20.71(10)† 148.9±22.0a(10) 237.1±29.81(10) 134.5±22.7a(10) 231.4±33.6a,1(10) 135.2±23.6a(10)
5 220.3±15.51(10) 105.2±12.8b(10) 230.0±46.21(10) 100.7±24.5b(10) 169.1±22.7b,2(10) 109.6±13.8b(10)
10 218.9±20.11(10) 99.6±10.4b,c(10) 222.3±39.51(10) 93.9±9.9b(10) 149.2±19.4b,c,2(10) 106.8±15.3b,c(10)
15 214.3±13.71(10) 92.2±9.5b,c,d(10) 213.7±35.81(10) 88.4±14.2b(10) 138.4±22.7c,d,2(10) 98.5±9.9b,c(10)
20 215.3±23.51(10) 93.4±9.5b,c,d(10) 210.9±43.21(10) 87.8±11.6b(10) 130.9±24.7c,d,2(10) 92.6±15.9b,c(10)
JOURNAL of the American Animal Hospital Association

30 214.0±22.91(10) 84.9±13.1b,c,d(10) 217.4±50.71(10) 85.3±10.3b(10) 123.8±20.4c,d,2(10) 90.9±10.3b,c(10)

40 229.5±28.31(10) 78.7±21.2c,d(10) 210.3±44.71(10) 84.0±9.3b(10) 123.8±19.0c,d,2(10) 109.6±13.9b,c(10)
50 236.5±29.11(10) 79.6±17.6c,d(10) 222.6±54.61(10) 81.4±11.7b(10) 116.2±13.6c,d,2(10) 87.7±11.3c (10)
60 232.4±29.51(9) 79.2±12.6c,d(9) 230.0±45.71(10) 80.6±11.9b(10) 122.8±13.3d,2(10) 87.0±10.0c (10)
70 228.3±29.2 1 (8) 71.5±14.5c,d,1(8) 242.1±52.11(7) 83.3±12.3b,1,2 (7) 122.1±14.1c,d,2(10) 90.3±10.1b,c,2(10)
80 236.6±30.9 1 (8) 82.0±21.4b,c,d (8) 231.6±61.7 1 (5) 84.0±15.5b (5) 126.6±12.7c,d,2(9) 88.9±14.9b,c(9)

* Pulse rate and systolic blood pressure of ferrets sedated with intramuscular diazepam (3 mg/kg body weight)-butorphanol (0.2 mg/kg body weight), acepromazine
(0.1 mg/kg body weight)-butorphanol (0.2 mg/kg body weight), or xylazine (2 mg/kg body weight)-butorphanol (0.2 mg/kg body weight) (all values are presented as
mean±standard deviation; columns of mean values with different numerical superscripts differ significantly [p<0.05]; rows of mean values with different alphabetic
superscripts differ significantly; rows of mean values without alphabetic superscripts are not significantly different)
†
Numbers in parentheses indicate the number of ferrets in recumbency
May/June 1998, Vol. 34
 May/June 1998, Vol. 34

Table 3
Effects of Anesthetics* on Respiratory Functions in Ferrets

Treatment Diazepam-Butorphanol Acepromazine-Butorphanol Xylazine-Butorphanol

Oxyhemoglobin Respiratory End-Tidal Oxyhemoglobin Respiratory End-Tidal Oxyhemoglobin Respiratory End-Tidal
Time Saturation Rate CO2† Saturation Rate CO2 Saturation Rate CO2
(min) (%) (breaths/min) (mmHg) (%) (breaths/min) (mmHg) (%) (breaths/min) (mmHg)
0 96.1±2.7(10) 62.7±21.2a(10)‡ 47.4±5.4a(10) 97.5±0.8a(10) 53.6±19.2a(10) 49.3±4.4a(10) 96.0±2.2a(10) 50.6±18.1a(10) 49.0±4.7a(10)
5 94.7±3.91(10) 19.7±6.4b,1(10) 52.9±3.3b(10) 95.4±2.9a,b,1 (10) 19.5±6.9b,1(10) 54.5±4.5b(10) 90.1±5.1b,2(10) 33.9±13.5b,2(10) 55.7±7.3b(10)
10 96.0±3.01(10) 16.6±6.9b,1(10) 55.1±3.8b,c,1 (10) 95.0±1.8a,b,1 (10) 18.8±8.5b,1(10) 56.1±4.0b,1(10) 89.0±7.2b,2(10) 30.4±7.5b,c,2 (10) 59.5±4.0b,c,2 (10)
15 96.9±2.01(10) 14.2±5.9b,1(10) 56.7±3.9b,c,d,1(10) 94.2±3.0b,1,2(10) 17.1±5.9b,1(10) 55.8±3.6b,1(10) 92.6±3.4a,b,2 (10) 30.8±6.6b,c,2 (10) 61.1±4.0c,2 (10)
20 96.4±3.21(10) 14.5±6.5b,1(10) 57.0±3.5c,d,1 (10) 95.8±1.1a,b,1,2(10) 16.3±6.1b,1(10) 56.9±4.1b,1(10) 92.5±4.6a,b,2 (10) 26.9±6.3b,c,2 (10) 61.7±3.3c,2 (10)
30 97.2±2.51(10) 14.1±6.1b,1(10) 58.1±5.7c,d,1,2(10) 95.7±2.1a,b,1,2(10) 18.8±2.9b,1(10) 56.7±4.5b,1(10) 93.1±4.7a,b,2 (10) 27.5±4.4b,c,2 (10) 62.1±3.6c,2 (10)
40 96.4±1.3(10) 16.7±7.5b,1(10) 57.0±5.1c,d,1 (10) 96.9±1.8a,b (10) 18.3±5.3b,1(10) 56.3±4.2b,1(10) 96.4±2.0b(10) 26.3±3.9b,c,2 (10) 61.9±2.9c,2 (10)
50 96.2±3.2(10) 15.0±7.0b,1(10) 57.7±3.1c,d,1 (10) 96.3±1.8a,b (10) 17.6±5.6b,1(10) 55.6±3.9b,1(10) 96.8±1.8b(10) 24.7±3.4b,c,2 (10) 61.9±3.5c,2 (10)
60 95.6±4.2(9) 16.2±5.2b,1(9) 58.2±4.3c,d,1,2(9) 96.9±2.3a,b (10) 17.1±5.7b,1(10) 56.2±5.7b,1(10) 96.7±2.4b(10) 23.0±3.2b,c,2 (10) 61.8±3.8c,2 (10)
70 96.4±2.3(8) 19.0±7.8b (8) 57.9±4.5c,d,1,2(8) 96.8±1.7a,b (7) 18.0±5.6b (7) 57.0±5.8b,1(7) 96.0±2.4b(10) 21.9±3.6b,c (10) 61.7±4.3c,2 (10)
80 96.1±1.9 (8) 26.4±15.9b (8) 59.3±3.8d (8) 97.3±84.0a,b (5) 19.0±6.4b (5) 59.0±5.6b (5) 96.6±2.4b (9) 20.4±3.3c(9) 61.3±4.9c(9)

* Oxyhemoglobin saturations, respiratory rates, and end-tidal carbon dioxide (CO2) concentrations of ferrets sedated with intramuscular diazepam (3 mg/kg body weight)-butorphanol
(0.2 mg/kg body weight), acepromazine (0.1 mg/kg body weight)-butorphanol (0.2 mg/kg body weight), or xylazine (2 mg/kg body weight)-butorphanol (0.2 mg/kg body weight) (all
values are presented as mean±standard deviation; columns of mean values with different numerical superscripts differ significantly [p<0.05]; rows of mean values with different
alphabetic superscripts differ significantly; rows of mean values without alphabetic superscripts are not significantly different)
†
CO2=carbon dioxide
‡
Numbers in parentheses indicate the number of ferrets in recumbency
Combination Sedation in the Ferret
247
248 JOURNAL of the American Animal Hospital Association
after injection [Table 3]. The lowest SpO 2 detected
was 89.0±7.2% in the xylazine-butorphanol-treated
ferrets at 10 minutes after injection. In all treatment
groups, SBP decreased significantly from the baseline.
The lowest SBP (71.5±14.5 mmHg) was recorded at
70 minutes postinjection in the diazepam-butor-
phanol-treated ferrets. There was a significant differ-
ence in the SBP between the diazepam-butorphanol-
and the xylazine-butorphanol-treated ferrets at 70
minutes [Table 2].
Cardiac arrhythmias, including respiratory sinus
arrhythmia and second-degree atrioventricular (AV)
blocks, were common. Respiratory sinus arrhythmia
occurred in all ferrets before and after drug adminis-
tration. Second-degree AV blocks occurred in all
treatment groups, but only after drug administration.
The AV heart blocks occurred sporadically during the
sedative period and frequently accompanied a sinus
arrhythmia. No other arrhythmias were observed.
Respiratory function was depressed in all groups.
Respiratory rate significantly decreased and remained
below the baseline values until the end of the experi-
ment [Table 3]. Respiratory rate was significantly
higher in the xylazine-butorphanol-treated ferrets than
in the diazepam-butorphanol- and acepromazine-
butorphanol-treated ferrets [Table 3]. End-tidal CO2
concentrations significantly increased from baseline
values in all groups and remained increased until the
end of the study. The xylazine-butorphanol-treated
ferrets had significantly higher end-tidal CO2 concen-
trations from 10-to-70 minutes following treatment,
suggesting that respiratory function was more de-
pressed in this group than in the other two groups
[Table 3].
Discussion
In the current study, all three drug combinations gen-
erally induced lateral recumbency in the ferrets within
six minutes. Two ferrets (one treated with the diaz-
epam-butorphanol combination and the other with the
acepromazine-butorphanol combination) did not be-
come recumbent until 12 and nine minutes, respec-
tively, after injection. The reason that these two ferrets
did not become recumbent in the same time period as
the others is not known precisely, but it could be
related to the weak sedative action of diazepam and
acepromazine. In contrast, the xylazine-butorphanol
combination consistently induced lateral recumbency
and was considered to be the most reliable combina-
tion. This was not surprising, because xylazine is a
potent sedative in the ferret when compared to diaz-
epam and acepromazine. 4
In the current study, the purpose of adding
butorphanol to diazepam, acepromazine, and xylazine
was to enhance their sedative and analgesic actions.
Most of the ferrets became laterally recumbent within
May/June 1998, Vol. 34
a reasonable time. The quality of sedation was im-
proved greatly by the addition of butorphanol, com-
pared to the quality of sedation observed in ferrets in
another study receiving diazepam, acepromazine, or
xylazine alone. 4 Butorphanol induces mild sedation
in dogs. 5 When butorphanol was combined with diaz-
epam, acepromazine, or xylazine, the duration of dorsal
recumbency was increased in the ferrets (diazepam-
butorphanol, 79.8±11.2 min; acepromazine-butor-
phanol, 65.7±17.5 min; xylazine-butorphanol, 82.3±4.9
min) as compared to the duration when diazepam
(43.2±8.2 min), acepromazine (49.8±11.9 min), or
xylazine (68.2±20.8 min) each were given alone. 4
Reportedly acepromazine, when given as a pre-
anesthetic, can prolong recovery; 6 but when given at
a dose of 0.1 mg/kg body weight, acepromazine did
not prolong recovery in ferrets. 4 In the current study,
the duration of dorsal recumbency and the time from
injection to complete remobilization was significantly
shorter in the acepromazine-butorphanol-treated fer-
rets than in the diazepam-butorphanol- or xylazine-
butorphanol-treated ferrets. The times from dorsal to
sternal recumbency and from sternal recumbency to
standing was not different among the three treatment
groups [Table 3]. This was a consistent finding 4 that
further supports the idea that acepromazine at 0.1 mg/
kg body weight does not prolong recovery in ferrets.
The short time from injection to remobilization seen
in the acepromazine-butorphanol-treated ferrets
mainly was due to their shorter duration of dorsal
recumbency.
Endotracheal intubation could not be achieved in
any of the ferrets in this study because of strong jaw
tone and consistent chewing motion. In a previous
study, 3 ferrets receiving medetomidine (80 µg/kg
body weight, IM) could not be intubated. However,
when butorphanol (0.1 mg/kg body weight, IM) was
given with medetomidine, ferrets could be intubated.
Endotracheal intubation in the previous study 3 ap-
pears to have been possible because of the potency of
medetomidine. The authors did not expect to be able
to intubate the ferrets in the current study, because
the neuroleptanalgesic combination only induces se-
dation and not general anesthesia.
Ferrets often require chemical restraint for routine
procedures, including nail clipping and ear cleaning.
In an earlier study, nail clipping and ear cleaning
were not possible in diazepam-treated ferrets and were
difficult to perform in those receiving acepromazine.4
In the current study, adding butorphanol to diazepam
or acepromazine provided sedation adequate for nail
clipping and ear cleaning procedures. This supports
the authors’ claim that butorphanol enhances the seda-
tive activity of the tranquilizers. The analgesic effect
of xylazine-butorphanol was profound and consis-
tent. In contrast, the diazepam-butorphanol combina-
May/June 1998, Vol. 34
tion induced no analgesia, and the acepromazine-
butorphanol combination induced minimal analgesia
with great variability. This was surprising because
butorphanol is considered a potent analgesic agent in
ferrets, 3 and analgesia was expected to be enhanced
further when combined with diazepam or acepro-
mazine. Duration of analgesia induced by xylazine-
butorphanol, as evaluated by toe (54.5±11.2 min),
skin (43.0±10.6 min), and tail (69.5±5.0 min) pinch
was longer than that induced by xylazine alone. Dura-
tion of analgesia induced by xylazine alone was
40.5±27.3, 32.5±18.1, and 35.8±17.4 minutes for toe,
skin, and tail pinches, respectively. 4 This is similar to
what was observed in a previous study 3 where the
duration of analgesia induced by medetomidine (80
µg/kg body weight, IM) was prolonged greatly (from
approximately 10 to 90 min duration) when butor-
phanol (0.1 mg/kg body weight, IM) was added.
It has been reported that ferrets anesthetized with
tiletamine-zolazepam, xylazine-ketamine, or tiletamine-
zolazepam-ketamine-xylazine experienced moderate-
to-profound salivation and frequent sneezing, despite
the coadministration of glycopyrrolate. 2 The sneez-
ing was attributed to upper airway irritation associ-
ated with salivation. 2 In the present study, sneezing
was not observed and salivation was minimal. Lack
of fasting prior to drug administration did not cause
any apparent adverse effects. Vomiting was not ob-
served in any of the ferrets. Similar results were
observed in ferrets sedated with medetomidine,3 diaz-
epam, acepromazine, or xylazine alone. 4
Pulse rate decreased significantly in the xylazine-
butorphanol-treated ferrets following drug adminis-
tration. Similar results were observed in ferrets treated
with xylazine alone, 4 medetomidine alone, and a
medetomidine-butorphanol combination. 3 This is at-
tributable to the vagal-mediated baroreceptor reflex
and subsequent sympatholysis of the alpha-2 agonists.7
Oxyhemoglobin saturation above 90% is accept-
able in the anesthetized animal. 10,11 Hypoxia devel-
ops rapidly when SpO 2 decreases below 90%, and
cell death can occur when SpO 2 is less than 85% for
one-to-two minutes. 11 Hemoglobin saturation values
of 70%, 80%, and 90% are approximately equal to
arterial partial pressure of oxygen values of 40, 50,
and 60 mmHg, respectively. 10,11 In the present study,
all three drug combinations decreased SpO 2 in ferrets
that breathed room air. The lowest recorded SpO 2 was
89.0±7.2% at 10 minutes in the xylazine-butorphanol-
treated ferrets. The pulse oximeter used to monitor
oxyhemoglobin in the present study underestimates
SpO 2 in ferrets when compared to arterial blood gas
values. A correction equation (51.60 + 0.5 x [pulse
oximeter reading]) is required to predict SpO 2 accu-
rately. 9 Using this equation (89.0±7.2%) resulted in
an SpO 2 that is higher than 90%, suggesting that the
Combination Sedation in the Ferret 249
xylazine-butorphanol-treated ferrets were not hy-
poxic. This is similar to previous observations in fer-
rets sedated with diazepam, acepromazine, or xylazine
in which none developed hypoxemia. 4
Systolic blood pressure significantly decreased
from the baseline in all treatment groups, with the
lowest SBP (71.5±14.5 mmHg) recorded 70 minutes
following diazepam-butorphanol administration. The
normal SBP range in anesthetized animals is between
100 and 160 mmHg. 8 A SBP below 80 mmHg is
assumed to result in inadequate cerebral and coronary
perfusion and may warrant therapy. 8 The technique
used to monitor blood pressure in the present study
has been shown to underestimate SBP by approxi-
mately 17 mmHg when compared with SBP taken
from the carotid artery. 9 Based on this information,
the diazepam-butorphanol-treated ferrets at 70 min-
utes were borderline hypotensive (SBP, 71.5+14.5
mmHg). Therefore, fluid administration, inotropic
drugs, or both may be indicated. The SBPs were lower
with butorphanol combinations than when the tran-
quilizers were given individually. When diazepam,
acepromazine, or xylazine was used as the sole drug,
the SBP ranged from 137.3±16.8 to 94.0±12.1 mmHg
with most values remaining above 100 mmHg. 4 The
lowest reading was in the xylazine-treated ferrets at
100 minutes after drug administration. In the current
study, the SBP ranged from 109.6±13.8 to 71.5±14.5
mmHg with most values below 100 mmHg. Clearly,
butorphanol did cause a decrease in blood pressure.
This is similar to the effects of butorphanol on arte-
rial blood pressure of dogs.5
Cardiac arrhythmias such as sinus arrhythmia and
second-degree AV heart blocks have been reported in
ferrets sedated with diazepam, acepromazine, or
xylazine at the identical doses used in this study.4
These arrhythmias were considered to be mediated
vagally. 4 Similar arrhythmias were observed in all
three treatment groups in the current study. It is pos-
sible that these arrhythmias were caused by the same
mechanism.
Ventilation was depressed in all treatment groups,
as evidenced by significant increases in end-tidal CO2
concentrations. The decreased respiratory function
also was indicated by significant decreases in RR in
all groups. The end-tidal CO 2 concentrations were
higher (between 10 and 70 min) in the xylazine-
butorphanol-treated ferrets than in the diazepam-
butorphanol- and acepromazine-butorphanol-treated
ferrets. This suggests that the respiratory depressant
effect of butorphanol is magnified when it is com-
bined with an alpha-2 agonist (e.g., xylazine). The
end-tidal CO2 concentrations in the xylazine-treated
ferrets of a previous study4 were lower than in the
xylazine-butorphanol-treated ferrets in the present
study. This further suggests that ventilatory efficiency
250 JOURNAL of the American Animal Hospital Association
is decreased when butorphanol is given in combina-
tion with xylazine.
Recovery in all three treatment groups was smooth.
The only concern was that three diazepam-butor-
phanol-treated ferrets developed lameness after re-
covery, possibly related to the large injection volume
of the diazepam-butorphanol combination. This cur-
rent study confirmed previous experiences with lame
ferrets that received diazepam. This possibly could be
caused by the large injected volume (approximately 1
ml) or it could be caused by local irritation to the
carrier, propylene glycol. 4 No severe adverse effects
were seen during the 24 hours postinjection, and all
three ferrets recovered uneventfully. The authors sug-
gest that when diazepam or a diazepam-containing
combination is used, the drug should be administered
in several separate injection sites to disperse the large
injection volume over a wider area and also to reduce
the possible irritation caused by the propylene glycol.
Conclusion
Diazepam, acepromazine, or xylazine, when combined
with butorphanol, are capable of inducing lateral re-
cumbency in healthy ferrets. The duration of dorsal
recumbency was significantly shorter in the acepro-
mazine-butorphanol-treated ferrets than in the diaz-
epam-butorphanol- or xylazine-butorphanol-treated
ferrets. None of the combinations induced a level of
sedation that would permit endotracheal intubation.
The best sedation was achieved with the xylazine-
butorphanol combination. The diazepam-butorphanol
combination provided the least amount of sedation.
Reliable analgesia was achieved in the xylazine-
butorphanol-treated ferrets but not in the diazepam-
butorphanol- or acepromazine-butorphanol-treated
ferrets. Hypoxemia did not develop in any of the
ferrets. Hypotension developed in the diazepam-
butorphanol-treated ferrets at 70 minutes postinjec-
tion. A profound respiratory sinus arrhythmia and
second-degree AV heart block commonly occurred in
all groups. Respiratory depression was observed in
all groups, especially in the xylazine-butorphanol
group. Recovery was smooth in all groups; however,
lameness was encountered in the three diazepam-
butorphanol-treated ferrets. Xylazine-butorphanol is
the most suitable neuroleptanalgesic combination for
healthy ferrets requiring chemical restraint or under-
going minor procedures. Sedation was improved and
its duration was extended when butorphanol was in-
cluded as part of the combination, compared to the
tranquilizer when used alone.
a
Angiocath; Becton-Dickinson, Sandy, UT
b
4000 Vet/Ox; Sensor Devices, Inc., Waukesha, WI
c
Disposa-Cuf, Neonatal #1 cuffs; Critikon, Inc., Tampa, FL
d
Model 5098.03; Ritter Tycos, Arden, NC
May/June 1998, Vol. 34
e
Model 811; Parks Medical Electronics Inc., Aloha, OR
f
Silver chloride ECG monitoring electrode; Medtek Southeast, Inc., St.
Petersburg, FL
g
Passport; Datascope Corp., Paramus, NJ
h
YSI Tele-Thermometer; Simpson Electric Co., Elgin, IL
i
Capnostat; Datascope Corp., Patamus, NJ
Acknowledgments
This experiment was supported by a grant from the
American Animal Hospital Association.
References
1. Gandolfi RC. The domestic ferret: a veterinary introduction. Calif Vet
1995;49(6):7–10.
2. Ko JCH, Pablo LS, Bailey JE, Heaton-Jones TG. Anesthetic effects of
Telazol, ketamine-xylazine and Telazol-ketamine-xylazine in ferrets.
Contemp Top Lab Anim Sci 1996;35(2):47–52.
3. Ko JCH, Heaton-Jones TG, Nicklin CF. Evaluation of the sedative and
cardiorespiratory effects of medetomidine, medetomidine-butorphanol,
medetomidine-ketamine, and medetomidine-butorphanol-ketamine in
ferrets. J Am Anim Hosp Assoc 1997;33:438–48.
4. Ko JCH, Nicklin CF, Heaton-Jones TG, Kuo WC. Comparison of
sedative and cardiorespiratory effects of diazepam, acepromazine, and
xylazine in ferrets. J Am Anim Hosp Assoc 1998;34:234–41.
5. Trim CM. Cardiopulmonary effects of butorphanol tartrate in dogs. Am
J Vet Res 1983;44:329–31.
6. Morrisey JK, Carpenter JW, Kolmstetter CM. Restraint and diagnostic
techniques for ferrets. Vet Med 1996;91(12):1084–97.
7. Thurmon JC, Tranquilli WJ, Benson GJ. Preanesthetics and anesthetic
adjuncts. In: Thurmon JC, Tranquilli WJ, Benson GJ, eds. Lumb &
Jones’ veterinary anesthesia. 3rd ed. Baltimore: Williams & Wilkins,
1996:183–209.
8. Haskins SC. Monitoring the anesthetized patient. In: Short CE, ed.
Principles and practice of veterinary anesthesia. Baltimore: Williams &
Wilkins, 1987:455–77.
9. Ko JCH, Harrison JM, Mladinich CHJ. Comparison of invasive and non-
invasive cardiopulmonary techniques in ferrets. Abstract, Proceed, 21st
Ann Am Coll Vet Anesth, New Orleans, LA 1996:45.
10. Ko JCH. Noninvasive techniques in monitoring anesthetized patients.
Vet Tech 1996;17(5):301–8.
11. LeBlanc PH, Sawyer DC. Electronic monitoring equipment. Semin Vet
Med Surg (Sm Anim) 1993;8:119–26.
 A Prospective Study of Survival and
Recurrence Following the Acute Gastric
Dilatation-Volvulus Syndrome in 136 Dogs
Dogs (n=136) with gastric dilatation-volvulus (GDV) syndrome were followed over
time to measure recurrence and mortality rates and to identify prognostic factors.
Thirty-three (24.3%) died or were euthanized during the first seven days. Of 85
cases that were followed for up to three years, nine (10.6%) cases each had a
recurrence of GDV and seven (8.2%) cases died or were euthanized. The median
survival times for cases that had gastropexies and those that did not were 547 and
188 days, respectively. Depressed or comatose cases on admission were three and
36 times, respectively, more likely to die than alert cases, while cases with gastric
necrosis were 11 times more likely to die. J Am Anim Hosp Assoc 1998;34:253–9.

Larry T. Glickman, VMD, DrPH Introduction

Gary C. Lantz, DVM
Diana B. Schellenberg, MS
Nita W. Glickman, MS, MPH
O are not well understood, specific risk factors have been identified.
From the Departments of Veterinary
Pathobiology (L. T. Glickman,
Schellenberg) and
Veterinary Clinical Sciences (Lantz) and
the Center for the Human-Animal Bond
(N. W. Glickman),
School of Veterinary Medicine,
Purdue University,
1243 Pathobiology Building,
West Lafayette, Indiana 47907-1243.
Gastric dilatation (GD) and gastric dilatation-volvulus (GDV) are
acute conditions of dogs characterized by a rapid accumulation of gas
or air in the stomach, increased intragastric pressure, a varying de-
gree of malposition of the stomach, and cardiogenic shock.1 It often is
not possible to distinguish GD from GDV solely on clinical signs;
however, both of these conditions may reflect the same underlying
disease process. While the etiology and pathogenesis of GD and GDV
These risk factors include being purebred and a large- or giant-breed
dog (especially one with a deep and narrow thorax), being older, and
having a first-degree relative that had GDV.2 More recently, con-
trolled epidemiologic studies showed that eating fewer meals per day
and a rapid rate of eating increased susceptibility to GDV, while dogs
characterized by their owners as happy or easygoing were at lower
risk than nervous or fearful dogs.3
Aggressive therapy is required for dogs showing signs of GD or
GDV. Initial treatment consists of gastric decompression and therapy
for shock to increase venous return to the heart.4 For dogs with
radiographic evidence of gastric rotation, the initial treatment should
be followed as soon as possible by surgical intervention aimed at
further decompressing and repositioning of the stomach, and gas-
tropexy to secure the stomach permanently in its normal position. The
common procedures for accomplishing gastropexy include right-side
tube gastropexy, circumcostal gastropexy, belt-loop gastropexy, and
incisional gastropexy. However, despite appropriate surgical inter-
vention and intensive postoperative care, case-fatality rates as high as
15% to 18% recently have been reported. 5,6
Two common questions asked of veterinarians by owners of dogs
diagnosed with GDV are “How much will the treatment cost?” and
“What is the likelihood that my dog will survive and lead a normal
life if it undergoes surgery?” An accurate answer to the latter ques-
tion requires knowledge by the veterinarian of the characteristics and
circumstances associated with either a poor or favorable prognosis
(i.e., the prognostic factors). The following study was conducted to

JOURNAL of the American Animal Hospital Association 253

254 JOURNAL of the American Animal Hospital Association
Figure 1—Flow chart of events in a prospective study of 136 dogs with acute gastric dilatation-volvulus (GDV).
identify the short- and long-term prognostic factors
for dogs with the GDV syndrome.
Materials and Methods
The cases in this study previously had been recruited
to participate in a case-control study of risk factors
for GDV.3 In brief, starting in 1991, dogs with a first
episode of GDV were identified by contacting several
large veterinary clinics in Indiana, Illinois, Ohio, and
Kentucky, as well as emergency clinics throughout
the United States. Veterinarians interested in partici-
pating were asked to complete a clinical data form for
all dogs that were diagnosed with GDV, based on
clinical, radiographic, and surgical findings and will-
ingness of their owners to be interviewed later by
telephone. When the researchers received a clinical
data form from a veterinarian, a consent form for a
telephone interview was mailed to the owner, and
arrangements were made for a specific time to con-
duct an initial interview. Owners who did not respond
to the first letter were contacted again by mail. Sub-
sequently, each owner who agreed to participate was
contacted again every few months to determine their
dog’s vital status, and if the dog was dead, the cause
of death. Causes of death were verified when neces-
sary by contacting the veterinarian responsible for
the dog’s care at the time of death. All of the
procedures used in this study were approved by the
Animal Care and Use Committee and by the Com-
May/June 1998, Vol. 34
mittee on the Use of Human Subjects of Purdue
University.
Data was analyzed using the SAS System for Win-
dows software. 7 Logistic regression analysis was used
to obtain odds ratios (ORs), 95% confidence limits
(CL), and probability (p) values for potential prog-
nostic factors for GDV. The OR in this context indi-
cates the probability of dying in the follow-up period
for cases with a specific characteristic (e.g., a certain
age or weight or severity of disease) when compared
with cases that did not have that particular character-
istic. An OR greater than 1.0 indicates an increased
risk of dying, while an OR less than 1.0 indicates a
decreased risk. If the CL of the OR excludes 1.0, then
the finding is statistically significant at p less than 0.05.
Survival curves were obtained using Kaplan-Meier
product-limit survival curve estimates.8 The log-rank
test was used to assess the difference in survival
times between cases with gastropexies and cases with-
out gastropexies.
Results
Completed clinical data forms were received from 27
veterinary clinics for 159 dogs with GDV. Informa-
tion regarding survival subsequently was obtained for
136 (85.5%) of these cases which formed the study
population. Of these 136 cases with GDV, 33 (24.3%)
died or were euthanized during the first seven days
following presentation to a veterinary clinic [Figure 1].
May/June 1998, Vol. 34 Gastric Dilatation-Volvulus Syndrome 255

Table 1
Characteristics of the 136 Dogs Enrolled in a Survival Study Following Gastric Dilatation-Volvulus

Age Weight
Total No. Gender Neutered (yrs) (lbs)
Breed Dogs Female Male Yes No (Mean±SD*) (Mean±SD)
Great Dane 23 10 13 9 14 5.7±2.8 123.9±19.0
German shepherd dog 15 4 11 5 10 7.0±3.3 81.8±16.6
Mixed-breed dog 13 5 8 9 4 8.4±4.3 63.1±26.2
Standard poodle 12 6 6 9 3 7.8±3.7 50.9±12.1
Doberman pinscher 11 6 5 7 4 8.6±2.1 74.9±14.1
Akita 6 2 4 5 1 2.8±2.2 91.7±22.1
Golden retriever 6 2 4 2 4 9.6±2.8 86.8±15.9
Irish setter 5 1 4 2 3 5.5±2.9 72.0±12.2
Other (25 breeds with 45 28 17 27 18 6.5±3.4 81.3±36.0
<5 dogs in each)
Total 136 64 72 75 61 6.8±3.4 84.3±32.4

* SD=standard deviation

Figure 2—Survival curves for two groups of dogs following an
acute episode of gastric dilatation-volvulus (GDV); =no gas-
tropexy (n=11), o=gastropexy (n=74).
Of the 103 surviving cases, 18 (17.5%) subsequently
were lost to follow-up. The remaining 85 cases were
followed for an average of 471 days (median, 416
days; minimum, 13 days; maximum, 1,170 days). Of
these 85 cases, nine (10.6%) cases had recurrences of
GDV; seven (8.2%) cases died or were euthanized
following the recurrence, while two (2.4%) cases sur-
vived. Nineteen (22.4%) cases died or were eutha-
nized for reasons unrelated to GDV.
The 136 cases in the study represented 33 different
breeds [Table 1]. The average age and weight±
standard deviation (SD) of these cases were 6.8±3.4
years and 84.3±32.4 lb., respectively. Sixty-four
(47.1%) were female, and 72 (52.9%) were male.
Seventy-five (55.1%) had been neutered surgically.
Short-Term Survival
The age, weight, sex, and neuter status of the cases
were not related significantly to their probability of
surviving the first seven days following acute GDV
[Table 2]. However, there was a trend of increasing
probability of death during this period with increas-
ing age at presentation. Cases greater than seven years
of age were 3.5 times more likely to die compared
with cases less than four years of age. Also, female
cases had an approximately 44% reduced risk of dying
compared with male cases. Neither of these trends with
regard to age or gender was statistically significant, but
they might warrant further investigation with a larger
number of cases. Neither the time from onset of GDV
(as determined by the owner) until the dog was pre-
sented to the veterinary clinic, nor the time from pres-
entation to the veterinary clinic to the time of surgery
were related significantly to the probability of dying.
The most striking prognostic factors for death dur-
ing the first seven days following GDV were all re-
lated to the severity of the case’s physical condition
at the time of presentation [Table 2]. Cases that were
recumbent upon presentation had a 4.4 times greater
probability of dying than those that were walking.
Cases that were judged by the veterinarian to be ei-
ther depressed or comatose were approximately three
and 36 times more likely to die, respectively, than
were alert cases. Also, based on the appearance of the
stomach at the time of surgery, cases with gastric necro-
sis had an approximately 11 times greater probability
of dying when compared to cases that had no evi-
dence of gastric necrosis.
256 JOURNAL of the American Animal Hospital Association May/June 1998, Vol. 34

Table 2
Factors Related to the Risk of Dying in the Seven Days Following
an Acute Episode of Gastric Dilatation-Volvulus

95%
Number of Dogs Confidence Probability
Prognostic Factor Survived Died Odds Ratio Limits Value
Age (yrs)
<4.0* 28 4 1.00 — —
4.0–6.9 26 6 1.62 0.35–7.84 0.73
7.0–8.9 22 11 3.50 0.86–15.31 0.08
>8.9 27 12 3.11 0.79–13.20 0.09
Weight (lbs)
<60* 26 6 1.00 — —
61–78 24 10 1.81 0.05–6.70 0.32
79–103 29 4 0.60 0.17–2.78 0.46
>104 22 12 2.36 0.67–8.57 0.13
Sex
Male* 51 21 1.00 — —
Female 52 12 0.56 0.23–1.35 0.16
Neutered
No* 46 15 1.00 — —
Yes 57 18 0.97 0.41–2.29 0.94
Onset to clinical presentation (hrs)
<1.0* 12 3 1.00 — —
1–2 44 11 1.00 0.21–5.38 1.00
>2.0 44 16 1.45 0.32–7.49 0.60
Presentation to surgery (hrs)
<1.0* 11 2 1.00 — —
1–2 52 3 0.32 0.04–3.13 0.22
>2.0 17 2 0.65 0.05–7.83 0.69
Mobility on presentation†
Walking* 92 21 1.00 — —
Recumbent 9 9 4.38 1.38–13.97 0.003
Responsiveness on presentation‡
Alert* 42 5 1.00 — —
Depressed 56 21 3.15 1.01–10.43 0.03
Comatose 0 4 35.83 3.03–974.26 <0.0001
Gastric necrosis at surgery
No* 74 4 1.00 — —
Yes 5 3 11.10 1.45–89.56 0.002

* Reference category
†
Does not include five dogs that were dead on arrival
‡
Does not include five dogs that were dead on arrival; data missing for three dogs

Recurrence of GDV and Long-Term Survival
Following Hospital Discharge
The age, weight, sex, and neuter status of the cases
were not related significantly to their probability of
having a recurrence of GDV. The exception was the
oldest cases, which were 12 times more likely to
suffer another episode of GDV compared with cases
less than four years of age [Table 3].
Gastropexy appeared to be very effective in pre-
venting a recurrence of GDV. In the cases that were
May/June 1998, Vol. 34 Gastric Dilatation-Volvulus Syndrome 257

Table 3
Factors Related to the Risk of a Recurrence of Gastric Dilatation-Volvulus
Following Treatment for an Acute Episode of Gastric Dilatation-Volvulus*

95%
Recurrence Confidence Probability
Prognostic Factor No Yes Odds Ratio Limits Value
Age (yrs)
<4.0† 23 0 1.00 — —
4.0–6.9 14 3 6.40 0.57–165.96 0.15
7.0–8.9 11 2 6.00 0.46–167.84 0.14
>8.9 9 4 12.00 1.08–309.63 0.02
Weight (lbs)
<60† 13 2 1.00 — —
61–78 12 1 0.54 0.02–9.12 1.00
79–103 20 4 1.30 0.16–12.13 1.00
>104 12 2 1.08 0.09–13.38 1.00
Sex
Male† 27 7 1.00 — —
Female 30 2 0.26 0.03–1.45 0.15
Neutered
No† 26 4 1.00 — —
Yes 31 5 1.05 0.21–5.30 1.00
Partial gastrectomy for necrosis
No† 52 9 1.00 — —
Yes 3 0 1.33 Undefined Undefined
Gastropexy
No† 5 6 1.00 — —
Yes 52 3 0.05 0.01–0.25 <0.001

* Does not include 19 dogs that were euthanized or died of causes other than GDV following discharge from the
hospital
†
Reference category

followed for a variable length of time after treatment, Discussion

the incidence of recurrence was 4.3% in the 74 cases
that had gastropexies versus 54.5% in the 11 cases
that did not have gastropexies. The types of
gastropexy performed in the cases, for which this
information was recorded, were incisional (n=28),
circumcostal (n=11), appositional (n=7), tube (n=4),
and other (n=19). Two (66.7%) of three cases that had
gastropexies died following a recurrence of GDV,
while five (83.3%) of six cases without gastropexies
died following recurrence. The survival curve for all
85 cases that were followed after acute GDV and
which died of any cause is shown in Figure 2. The
median survival time for the 74 cases that had any
type of gastropexy was 547 days versus 188 days for
the 11 cases that did not have gastropexies, and this
difference was highly significant (p of 0.0001).
Of the 136 cases with GDV in this study, 33 (24.3%)
died within the first seven days following onset of
clinical signs, and this included 15 cases that were
euthanized before treatment. An overall mortality rate
of 33.3% was reported previously in a retrospective
study of 1,934 dogs with GDV brought to veterinary
teaching hospitals in the United States. 2 While the
reasons for euthanasia were not determined in these
studies, they presumably involved either the severity
of the disease or financial concerns. Regardless of the
reasons for euthanasia, a significant number of dogs
that develop GDV will die shortly after the acute
episode.
If the 15 (11%) cases that were euthanized before
treatment in this study are removed from consider-
258 JOURNAL of the American Animal Hospital Association
ation, the short-term mortality rate would be reduced
to 13.2%. This compares with a mortality rate of
15.0% found by Brockman 5 for 193 dogs (mean age,
7.3 yrs) with GDV that were treated surgically at the
University of Pennsylvania Veterinary Hospital, and
a mortality rate of 17.5% for 137 dogs (mean age, 6.8
yrs) with GDV that were treated surgically at either a
university teaching hospital or a private clinic.6 In
general, these findings indicate that once dogs are
selected for surgery, their chances of surviving in the
near term are about 85%.
Not all dogs have the same probability of surviv-
ing treatment for GDV. In the study reported here,
there was a statistically significant increase in GDV
mortality associated with the case’s physical condi-
tion; cases that were either depressed or comatose
when first seen by a veterinarian had a 3.2 and 35.8
times greater probability, respectively, of dying than
cases that were alert. Also, cases with gastric necro-
sis found at surgery were 11.1 times more likely to
die. There was an increased probability of dying for
older cases and for male cases, but these increases
were not statistically significant. A study of GDV in
the Netherlands similarly found that mortality fol-
lowing GDV is highly correlated with the dog’s state
of consciousness prior to treatment; alert dogs had a
mortality rate of 6% versus greater than 37% in de-
pressed dogs, and mortality also was related to pulse
rate, pulse quality, color of mucous membranes, and
capillary refill time. 9
In this study, the time from onset of clinical signs
to presentation to a clinic and the time from admis-
sion to a clinic to the time of surgery were not associ-
ated with outcome. A study of 60 dogs with GDV at a
university hospital in the Netherlands 10 found that
mortality rates in dogs having short and long inter-
vals from first signs to surgery and from emergency
treatment to surgery were not significantly different.
Another study of 193 dogs with GDV 5 similarly found
no association of short-term survival from GDV and
age of the dog, time from onset of clinical signs to
admission, and time from admission to surgery. This
study also did not find that cardiac arrhythmia was
associated with an unfavorable outcome. In contrast,
others6 have reported mortality rates as high as 38%
in dogs with preoperative cardiac arrhythmias. While
it is not known why a shorter time from onset of
clinical signs to veterinary intervention is not associ-
ated with a better prognosis, it is possible that dogs
with more rapid progression of clinical signs (and
thus more severe underlying disease) also are more
likely to be recognized by their owners and receive
medical care sooner than are those dogs with mild
signs for which underlying disease is less severe.
Thus, in observational studies of GDV treatment, time
to treatment will be confounded by severity of dis-
May/June 1998, Vol. 34
ease. In contrast, in this and several other studies, 5,6
the presence of gastric necrosis at surgery for GDV is
associated consistently with a much higher risk of
dying. When the clinician is confronted with a dog
having signs of GDV, understanding the progressive
nature of the disease underscores the need for early
diagnosis and rapid medical and surgical interven-
tion. The timing of surgery depends on initial patient
evaluation, response to preoperative treatment, and
radiographic confirmation of gastric volvulus. Most
clinicians support exploratory surgery including stom-
ach repositioning and creation of a permanent gas-
tropexy as soon as the patient is determined to be a
reasonable anesthetic risk.
For the 85 cases with GDV in this study that were
followed over time, the recurrence rate was 54.5% for
those cases that did not have gastropexies performed
and only 4.3% for those that did, which represents a
92% reduction in risk of recurrence with gastropexy.
The median survival times for these two groups of
cases were 188 days and 547 days, respectively, and
this difference was highly significant. Only the oldest
cases (more than 8.9 years of age) were at a statisti-
cally elevated risk of recurrence, and the risk in fe-
male cases was reduced by 74%. It is possible that
had the cases been followed for a longer period of
time, the recurrence and mortality rates would have
been substantially higher, since the risk of GDV in-
creases with increasing age. 2 Regardless of the type
of treatment, a majority of cases that had recurrences
of GDV died. Gastric dilatation and GDV most likely
have the same underlying etiology. Therefore, it may
be prudent to consider gastropexy in cases that present
with GD without volvulus. In such cases, the proce-
dure could be performed as an elective surgery shortly
after patient recovery for the GD episode.
The findings of this study with regard to long-term
recurrence and mortality following GDV are similar
to previous retrospective studies and randomized
clinical trials. For example, Eggertsdottir and Moe 11
in a retrospective study of 103 dogs with GDV at a
veterinary teaching hospital in Norway found a recur-
rence rate of 56% during the first three months fol-
lowing conservative treatment consisting of shock
therapy and gastric decompression, and all but two
cases had recurrences of GDV when followed for one
year. When conservative therapy was compared to
gastropexy in a retrospective review of 134 dogs with
GDV,12 the recurrence rate was 75.8% with conserva-
tive therapy and 6.6% with gastropexy. When a ran-
domized controlled trial was conducted comparing
conservative therapy for GDV with circumcostal gas-
tropexy, the median survival times were 107 days and
549 days, respectively.13 Thus, it is clear that shock
therapy and gastric decompression should be consid-
ered only as first aid for dogs with GDV, and some
May/June 1998, Vol. 34
form of gastropexy is needed to prevent a recurrence
and reduce mortality.
Gastropexy is intended to create a permanent ad-
hesion between the stomach and body wall. The py-
loric antral region of the stomach is fixed to the
adjacent right abdominal wall, because some gastric
rotation still may occur if gastropexy is performed on
the left side. The common procedures for gastropexy
include right-sided tube gastrostomy (i.e., tube gas-
tropexy), 14,15 circumcostal gastropexy,16,17 belt-loop
gastropexy, 18 and incisional gastropexy. 19 Random-
ized controlled trials comparing different types of
gastropexy have not been conducted. Therefore, at
this time, the choice of a particular gastropexy tech-
nique is largely a personal preference. The surgeon
should be familiar with not only the specific tech-
nique but also its advantages, potential complications,
and failure rates, which are in the range of 3% to 8%.
Conclusion
The general physical condition of the dog along with
the appearance of the stomach at surgery are the best
short- and long-term prognostic factors. Older age
alone is not a contraindication for surgical interven-
tion. While the time from onset of clinical signs to
medical and surgical treatments has not been associ-
ated with prognosis, dog owners (especially those
who own breeds at the highest risk of GDV) should
be educated to recognize the earliest signs of GDV
and the need for immediate emergency gastric de-
compression and treatment. There is presently insuf-
ficient data to recommend one method of gastropexy
over another, and randomized controlled trials are
needed to distinguish their efficacy. Improvements in
medical and surgical treatments of GDV over time
have improved survival rates significantly, but more
studies are needed regarding disease prevention since
mortality for GDV remains around 15% with current
treatments.
Acknowledgments
Supported in part by funds from the Morris Animal
Foundation, the American Kennel Club Canine Health
Foundation, the Irish Setter Club of America, and
many dog breeders and owners.
References
1. Burrows CG, Ignaszewski A. Canine gastric dilatation-volvulus.
J Sm Anim Pract 1990;31:495–501.
2. Glickman LT, Glickman NW, Perez CM, Schellenberg DB, Lantz GC.
Analysis of risk factors for gastric dilatation and dilatation-torsion in
dogs. J Am Vet Med Assoc 1994;204:1465–71.
3. Glickman LT, Glickman NW, Schellenberg DB, Simpson K, Lantz GC.
Multiple risk factors for gastric dilatation-torsion syndrome in dogs: a
practioner/owner case-control study. J Am Anim Hosp Assoc
1997;33:197–204.
Gastric Dilatation-Volvulus Syndrome 259
4. Lantz GC. Treatment of gastric dilatation-volvulus syndrome. In: Bojrab
MJ, Birchard SJ, Tomlinson JL Jr., eds. Current techniques in small
animal surgery. 3rd ed. Philadelphia: Lea & Febiger, 1990:224–31.
5. Brockman DJ, Washabau RJ, Drobatz KJ. Canine gastric dilatation/
volvulus syndrome in a veterinary critical care unit: 295 cases (1986–
1992). J Am Vet Med Assoc 1995;207:460–4.
6. Brourman JD, Schertel ER, Allen DA, Birchard SJ, DeHuff WD. Factors
associated with perioperative mortality in dogs with surgically managed
gastric dilatation-volvulus: 137 cases (1988–1993). J Am Vet Med
Assoc 1996;207:1855–8.
7. SAS/STAT User’s Guide (Vol. 2). Cary, NC: SAS Institute, 1990:
1071–126.
8. Lee ET. Statistical methods for survival data analysis. 2nd ed. New
York: John Wiley-Interscience, 1992:109–12.
9. Van Sluijs FJ. Gastric dilatation-torsion in the dog: current views and a
retrospective study in 160 patients. Tijdschr Diergeneeskd 1991;
116:112–21.
10. Van Sluijs FJ. Gastric dilatation-volvulus in the dog. PhD thesis, Faculty
of Veterinary Medicine, University of Utrecht, the Netherlands,
1987:31–128.
11. Eggersdottir AV, Moe L. A retrospective study of conservative treat-
ment of gastric dilatation-volvulus in the dog. Acta Vet Scand
1995;36:175–84.
12. Meyer-Lindenberg A, Harder A, Fehr M, Luerssen D, Brunnberg L.
Treatment of gastric dilatation-volvulus and a rapid method for preven-
tion of relapse in dogs: 134 cases (1988–1991). J Am Vet Med Assoc
1993;203:1303–7.
13. Eggersdottir AV, Stigen O, Lonase L, Kolvjornsen O, Moe L. Compari-
son of two surgical treatments of gastric dilatation-volvulus in dogs.
Acta Vet Scand 1996;37:415–26.
14. Flanders JA, Harvey HJ. Results of tube gastrostomy as treatment for
gastric torsion in the dog. J Am Vet Med Assoc 1984;185:74–7.
15. Johnson RG, Barrus J, Greene RW. Gastric dilatation-volvulus: recur-
rence rate following tube gastrostomy. J Am Vet Med Assoc 1984;
20:33–7.
16. Live MS, Konde LJ, Wingfield WE, Twedt TC. Circumcostal gastropexy
for preventing recurrence of gastric dilatation-volvulus in the dog: an
evaluation of 30 cases. J Am Vet Med Assoc 1985;187:245–8.
17. Woolfson JM, Kostolich M. Circumcostal gastropexy: clinical use of the
technique in 34 dogs with gastric dilatation-volvulus. J Am Anim Hosp
Assoc 1986;22:825–30.
18. Whitney WO, Scavelli TD, Matthiesen DT, Burk RL. Belt-loop gas-
tropexy: technique and surgical results in 20 dogs. J Am Anim Hosp
Assoc 1989;25:75–83.
19. MacCoy DM, Sykes GP, Hoffer RE, Harvey HJ. A gastropexy technique
for permanent fixation of the pyloric antrum. J Am Anim Hosp Assoc
1982;18:763–8.
 Triple Pelvic Osteotomy:
Effect on Limb Function and
Progression of Degenerative Joint Disease
The objective of this study was to evaluate prospectively the outcome of 21 clinical
patients treated with triple pelvic osteotomies during the year following surgery.
Specific aims included documenting the time of and extent of improved limb function
as measured by force plate analysis, evaluating the progression of degenerative joint
disease (DJD) in the treated and untreated coxofemoral joints, and determining
whether or not triple pelvic osteotomy resulted in degenerative joint changes in the
ipsilateral stifle and hock.
Twelve dogs were treated unilaterally and nine dogs were treated bilaterally with
triple pelvic osteotomies. There were no differences in mean anteversion angles,
angles of inclination, or preoperative DJD between treated hips and untreated hips.
Degenerative joint disease progressed significantly in all hips regardless of
treatment. Two cases developed hyperextension of their hocks after the triple pelvic
osteotomies. However, no radiographic evidence of DJD was observed for any of the
stifles or hocks at any observation time. A significant increase in vertical peak force
(VPF) scores was noted for treated legs by two-to-three months after surgery, which
continued over time. Untreated legs did not show a significant change in VPF scores
over time. No differences were found in progression to higher scores when
unilaterally treated legs, first-side treated legs, and second-side treated legs were
compared. J Am Anim Hosp Assoc 1998;34:260–4.

A. L. Johnson, DVM, MS, Introduction

Diplomate ACVS
C. W. Smith, DVM, MS,
Diplomate ACVS
G. J. Pijanowski, DVM, PhD
L. L. Hungerford, DVM, PhD
O magnitude of forces acting on the hip joint to effect these beneficial
From the Departments of Veterinary
Clinical Medicine (Johnson, Smith,
Hungerford) and
Veterinary Biosciences (Pijanowski),
College of Veterinary Medicine,
University of Illinois,
1008 Hazelwood Drive,
Urbana, Illinois 61801.
Triple pelvic osteotomy was described first by Hohn and Janes in
1969 as an alternative to femoral head and neck ostectomy or pros-
thetic replacement for canine hip dysplasia. 1 The procedure has been
modified and frequently is used to treat immature dogs with coxo-
femoral joint subluxation and minimal or no radiographic evidence of
degenerative joint disease (DJD). 2–6 The expected outcomes for dogs
treated with triple pelvic osteotomy are improved function of the limb
and minimized progression of DJD in the hip.6 Theoretically, triple
pelvic osteotomy increases femoral head coverage and reduces the
clinical results. 7 The effects of triple pelvic osteotomy on the ipsilat-
eral stifle and hock have not been evaluated.
Limb function assessed with force plate analysis approached or
reached control levels by 28 weeks after surgery in 15 dogs with
bilateral hip dysplasia.8 Subjective assessments of limb function over
longer times show “satisfactory,” or “normal-to-near normal” func-
tion in most clinical patients.3,5 Although improved hip congruence
has been reported in most studies, progression of secondary DJD
varies from minimal-to-moderate osteophyte formation over times
ranging from three months to five years. 3,5,6,8–10 Complications in-
clude implant failure, pelvic canal stenosis, sciatic nerve damage, and
hyperextension of the hock. 3,5,10–12

260 JOURNAL of the American Animal Hospital Association

May/June 1998, Vol. 34
Appendix
Criteria for Degenerative Joint Disease
(DJD) Scoring
Hip
1 = Normal
2 = Incongruity only
3 = Mild degenerative changes
(early osteophytes, roughening along joint capsule
margins)
4 = Moderate degenerative changes
(obvious osteophytes)
5 = Severe degenerative changes
(large osteophytes, change in the joint shape,
marked subchondral sclerosis)
6 = Very severe degenerative changes
(large osteophytes on acetabular margin and
femoral neck, loss of joint space, severe subchon-
dral sclerosis)
Stifle
1 = Normal
2 = Soft-tissue swelling only
3 = Mild degenerative changes
(early osteophytes, roughening along joint capsule
margins)
4 = Moderate degenerative changes
(obvious osteophytes)
5 = Severe degenerative changes
(obvious osteophytes, change in the joint shape,
marked subchondral sclerosis)
6 = Very severe degenerative changes
(large osteophytes, loss of joint space, severe
subchondral sclerosis)
Hock
1 = Normal
2 = Soft-tissue swelling only
3 = Mild degenerative changes
(early osteophytes, roughening along joint capsule
margins)
4 = Moderate degenerative changes
(obvious osteophytes)
5 = Severe degenerative changes
(obvious osteophytes, change in the joint shape,
marked subchondral sclerosis)
6 = Very severe degenerative changes
(large osteophytes, loss of joint space, severe
subchondral sclerosis)
The objective of this study was to evaluate pro-
spectively the outcome of 21 clinical patients treated
with triple pelvic osteotomies during the year follow-
ing surgery. Specific aims included documenting the
Triple Pelvic Osteotomy 261
time of and extent of improved limb function as mea-
sured by force plate analysis, evaluating the progres-
sion of DJD in the treated and untreated coxofemoral
joints, and determining if triple pelvic osteotomy re-
sulted in degenerative joint changes in the ipsilateral
stifle and hock.
Materials and Methods
All immature, large dogs presenting to the University
of Illinois Veterinary Medical Teaching Hospital over
a two-year period which were showing signs of rear
limb lameness caused by canine hip dysplasia were
evaluated for inclusion in this study. Each dog which
qualified for the study had radiographic evidence of
coxofemoral joint subluxation with minimal-to-no
DJD and a positive Ortolani’s sign. A physical ex-
amination was done to rule out the presence of other
orthopedic abnormalities. The dog had to be willing
to trot over the force plate. Additionally, the owners
had to be willing to return their dogs for reevalua-
tions and give informed consent for their dogs to
participate in the study. Based on these criteria, 21
dogs (mean age, 8.9 months; range, seven to 12
months) were identified for the study.
The preoperative, radiographic examination con-
sisted of a ventrodorsal view of the pelvis with each
dog positioned for standard hip dysplasia evaluation,
lateral views of both femurs, and craniocaudal and
lateral views of the stifles and hocks. The images
were evaluated for signs of DJD. Angles of antever-
sion and inclination for all femoral heads were calcu-
lated from the ventrodorsal and lateral views of the
femurs.13 Postoperative radiographs of the pelvis were
evaluated for implant position. Owners were requested
to return their dogs for reevaluation and radiographs
of the pelvis at one, two, four, six, and 12 months
after surgery. Radiographs of the stifles and hocks
were repeated at six and 12 months after surgery.
Radiographs of each dog were evaluated by three
independent observers, blinded to individual dogs and
postoperative times. Signs of DJD in the hips, stifles,
or hocks were noted. Scores were assigned on the
basis of evidence of instability and DJD according to
a predetermined scale [see Appendix]. The mean of
the three observations was used as the DJD score for
each dog at each observation point.
Force plate analysis was performed preoperatively,
and the owners were requested to return their dogs for
reevaluation one, two, four, six, and 12 months after
surgery. The dogs were trotted on lead at their own
natural speed across an AMTI OR 6-3A force plate a
to measure ground reaction forces (GRFs). The active
area of the force plate (29.2 by 29.2 cm) was located
in the center of a 4.3-m walkway. Two photoelectric
cells, located 1 m on either side of the force plate,
were used to trigger the beginning and end of data
262 JOURNAL of the American Animal Hospital Association
Table 1—Graph of degenerative joint disease (DJD) scores
over time for 21 dogs treated with triple pelvic osteotomies.
(The n values for groups evaluated for DJD may differ from
the n values for groups evaluated for vertical peak force (VPF)
scores because of difficulties obtaining data.)
collection and to determine the dog’s speed. Output
from the force plate was sampled at 1 kHz with a 12-
bit analog to digital converter b controlled by a Zenith
248 (AT-style) computer. c The GRF was scaled to
body weight (BW) and reported as newton force per
newton BW. Vertical peak force (VPF) scores were
used to assess limb function. Each dog was trotted
over the force plate numerous times to obtain clear
strikes of each foot within the area of the force plate.
A minimum of six recordings of the GRF from each
foot were obtained, and the mean was used as the
VPF score for each dog at each time point.
The angles of subluxation and reduction were de-
termined, and the appropriate canine pelvic osteotomy
plate d (30˚ plate, n=26; 20˚ plate, n=2; 40˚ plate, n=1;
45˚ plate, n=1) was selected.6 A triple pelvic osteotomy
was performed to treat the limb for which the dog
showed the most severe clinical signs of lameness. 6 If
the owners opted to have surgical treatment for the
contralateral hip, a triple pelvic osteotomy was per-
formed two months after the initial procedure.
The anteversion angles, angles of inclination, and
preoperative DJD scores were compared for treated
and untreated hips using the Wilcoxon’s paired signed
rank test. The observation points were grouped as
two-to-three months after surgery, four-to-six months
after surgery, and 10-to-12 months after surgery be-
cause of the variation in actual (versus requested)
reevaluation times. Group means were calculated for
DJD and VPF scores of all legs which received the
same type of treatment and were graphed over time.
The groups included treated legs of dogs undergoing
unilateral surgery (n=8); legs treated first in dogs
undergoing bilateral surgery (n=9); legs treated sec-
ond in dogs undergoing bilateral surgery (n=6); and
untreated legs of dogs undergoing unilateral surgery
(n=10). The inconsistencies in treatment numbers
were due to lack of data in cases for which the owners
May/June 1998, Vol. 34
failed to return the dogs for all of the postsurgical
radiographs and force plate examinations. Changes in
DJD and VPF scores for all legs, for treated legs, and
for untreated legs were evaluated separately (using
Wilcoxon’s paired signed rank tests) for each postop-
erative time relative to preoperative time (i.e., two-
to-three months, four-to-six months, and 10-to-12
months after surgery). 14 Changes in DJD and VPF
scores for each postoperative time relative to preop-
erative period were compared between all treated and
untreated legs using Wilcoxon’s paired signed rank
tests. 14 For dogs with unilateral pelvic osteotomies,
the amount of change in DJD and VPF scores from
preoperative to later time periods was compared be-
tween the treated and untreated legs using Wilcoxon’s
paired signed rank tests. A p value of less than 0.01
was considered to be statistically significant.
Results
Of the 21 dogs enrolled in the study, 12 dogs were
treated unilaterally and nine dogs were treated bilat-
erally with triple pelvic osteotomies. The mean ante-
version angle for all femoral heads was 35.4˚ (median,
34.3˚; range, 26.6˚ to 48.4˚). The mean anteversion
angle of femoral heads of treated hips was 35.5˚ (me-
dian, 33.8˚; range, 26.6˚ to 48.4˚). The mean antever-
sion angle for femoral heads of untreated hips was
35.6˚ (median, 34.9˚; range, 28˚ to 45˚). The mean
angle of inclination for all femoral heads was 142.2˚
(median, 141.2˚; range, 122˚ to 165.1˚). The mean
angle of inclination of femoral heads of treated hips
was 142.1˚ (median, 141.4˚; range, 122˚ to 165.1˚).
The mean angle of inclination for femoral heads of
untreated hips was 142.4˚ (median, 140.6˚; range,
132.3˚ to 159.9˚). No differences were detected be-
tween treated hips and untreated hips.
The mean and median preoperative radiographic
scores for all hips were 2.7 (range, 1.3 to 5). The
mean and median preoperative radiographic scores
for treated hips were 2.7 (range, 2.0 to 3.7). The mean
and median preoperative radiographic scores for un-
treated hips were 2.7 (range, 1.5 to 5). No differences
were detected in mean preoperative DJD scores be-
tween the three groups of all hips, treated hips, and
untreated hips. Degenerative joint disease progressed
significantly in all hips regardless of treatment [Table
1]. Although the graphed data appeared to show a
trend toward increased DJD scores in untreated hips,
there was no significant difference between treated
hips and untreated hips over the three time intervals for
all dogs. No significant differences were detected
between treated hips and untreated hips when the
group of dogs treated with unilateral osteotomies was
evaluated.
Two dogs each developed bilateral hyperextension
of the hocks after bilateral triple pelvic osteotomies.
May/June 1998, Vol. 34
Table 2—Graph of vertical peak force (VPF) scores obtained
with force plate analysis over time. (The n values for groups
evaluated for DJD may differ from the n values for groups
evaluated for VPF scores because of difficulties obtaining data.)
However, no radiographic evidence of DJD was ob-
served in any of the stifles or hocks.
When the group of all dogs was evaluated, VPF
scores increased significantly in treated legs by two-
to-three months after surgery and continued to in-
crease over time. Untreated legs did not show a
significant change in VPF scores over time. The
graphed data showed a trend for decreasing VPF
scores by the two-to-three month evaluation time for
the untreated limbs [Table 2]. There was no difference
in progression to higher scores when unilaterally
treated legs, first-side treated legs, and second-
side treated legs were compared. A trend toward im-
provement in the treated legs which increased over
time was observed for the group of dogs (n=8) treated
unilaterally. The changes in VPF scores for the treated
legs were greater than the changes in VPF scores for
the untreated legs. This difference was not significant
at the two-to-three month evaluation (p of 0.08) but
was significant at the two later evaluation periods (p
of 0.04 at four-to-six months and p of 0.02 at 10-to-
12 months).
Discussion
The dogs included in this study were selected as can-
didates for triple pelvic osteotomy because they met
criteria (e.g., clinical signs of lameness, radiographic
evidence of hip dysplasia with minimal degenerative
changes, and a positive Ortolani’s sign) indicative for
such treatment. This preliminary screening selected a
population of immature dogs with hips which were
similar initially. Therefore, the authors expected no
differences in angles of anteversion, angles of incli-
nation, and preoperative radiographic scores between
treated and untreated hips in this study. Clinical lame-
ness rather than radiographic criteria often was the
deciding factor for owners to choose surgical treat-
ment for their dogs. Also, the owners’ wishes deter-
Triple Pelvic Osteotomy 263
mined if bilateral triple pelvic osteotomies were per-
formed. However, the anteversion angles and angles
of inclination of the treated hips were similar to those
described in previous case studies. 3 In particular, the
anteversion angles of treated hips were, with one
exception, within the 45˚ cited as acceptable for hips
treated with triple pelvic osteotomy.6
The mean preoperative DJD scores indicated that
the dogs in this study generally had some radiographic
evidence of DJD before surgery was performed. The
radiographic evidence of DJD (as assessed by the
mean radiographic scores) progressed regardless of
treatment. However, when the data was graphed, there
was a trend toward higher radiographic scores over
time for untreated hips. This trend may become signifi-
cant with larger numbers or longer follow-up times.
It has been reported that the progression of DJD is
halted or diminished after triple pelvic osteotomy. 5,6
Improved hip congruence has been reported 9,10 with
moderate progression of osteophyte formation after
three months10 and mild progression in 28% of treated
hips at six months.8 Gross and microscopic degenera-
tive changes in articular cartilage were similar for
treated and untreated hips in three dogs evaluated 28
weeks after surgery, although consistently more reac-
tivity in the synovial membrane was observed in un-
treated hips. 8 The ideal candidate for triple pelvic
osteotomy has been proposed as a dog with mild
subluxation of the femoral head and no radiographic
evidence of osteophytosis or damage to the dorsal rim
of the acetabulum. 6 It is possible that progressive
DJD develops in hips which already have radiographic
signs of osteophytosis prior to surgery but does not
develop in hips which do not have radiographic signs
of osteophytosis prior to surgery.
Despite progressive DJD, mean VPF scores in-
creased significantly over time for all treated legs.
The mean VPF scores for the untreated legs decreased
over time until, at six months after surgery, the mean
VPF scores of treated and untreated limbs in dogs
treated with unilateral triple pelvic osteotomy were
similar. The mean VPF scores for treated legs in dogs
treated bilaterally also stabilized by six months after
surgery but were higher than the scores for the unilat-
erally treated dogs. The first surgery always was per-
formed on the limb for which the dog showed more
severe clinical signs of lameness. This is reflected in
the difference in the preoperative VPF scores be-
tween the treated and untreated limbs for unilaterally
treated dogs. After surgery, the VPF scores of the
limbs converged, indicating the willingness of the
dog to use the treated limb more normally in spite of
progressive DJD. A similar pattern is seen in the
bilaterally treated cases.
The range of VPF scores for normal canine hind
limbs is 60% to 70% of total BW. 15 Previously, evalu-
264 JOURNAL of the American Animal Hospital Association May/June 1998, Vol. 34

ation of limb function of 15 dogs by force plate analy-
sis documented return to the level of forces transmit-
ted through the treated hips, reaching or approaching
control levels by seven months after surgery. 8 Similar
outcome has been documented subjectively when 106
dogs were observed one year after triple pelvic os-
teotomy. In this study, 86.2% of the dogs showed
normal or near-normal function of the treated limb,
while 12% showed improved function of the limb. 5
Owners have observed that triple pelvic osteotomy
resulted in an abnormal gait.3 Changing the orienta-
tion of the pelvis reduces the magnitude of forces
acting on the hip. 7 Reorienting the pelvic position
may change the limb orientation and did appear to
affect the position of the hocks in two cases in this
study. However, if there are changes in the forces
directed through the stifle and hock of dogs treated
with triple pelvic osteotomy, they do not result in
radiographic signs of DJD.
8. McLaughlin RM, Miller CW, Taves CL, Hearn TC, Palmer NC, Ander-
son GI. Force plate analysis of triple pelvic osteotomy for the treatment
of canine hip dysplasia. Vet Surg 1991;20:291–7.
9. McLaughlin RM, Miller CW. Evaluation of hip joint congruence and
range of motion before and after triple pelvic osteotomy. Vet Comp
Ortho Trauma 1991;4:65–9.
10. Koch DA, Hazewinkel HAW, Nap RC, Meij BP, Wolvekamp WThC.
Radiographic evaluation and comparison of plate fixation after triple
pelvic osteotomy in 32 dogs with hip dysplasia. Vet Comp Orthop
Trauma 1993;6:9–15.
11. Hosgood G, Lewis DD. Retrospective evaluation of fixation complica-
tions of 49 pelvic osteotomies in 36 dogs. J Sm Anim Pract 1993;
34:123–30.
12. Remedios AM, Fries CL. Implant complications in 20 triple pelvic
osteotomies. Vet Comp Orthop Trauma 1993;6:202–7.
13. Montavon PM, Hohn RB, Olmstead ML. Inclination and anteversion
angles of the femoral head and neck in the dog. Vet Surg 1985;
14:277–82.
14. Zar JH. Biostatistical analysis. 2nd ed. Englewood Cliffs, NJ: Prentice-
Hall, 1984:138–46, 153–6.
15. Rumph PE, Lander JE, Kincaid SA, Baird DK, Kammermann JR, Visco
DM. Ground reaction force profiles from force platform gait analysis of
clinically normal mesomorphic dogs at the trot. Am J Vet Res
1994;55:756–61.

Conclusion
Triple pelvic osteotomy did not alter the progression
of DJD significantly in this population of dogs but
was successful in eliminating lameness by six months
after surgery, as evidenced by increased VPF scores
over time. Degenerative joint disease did not develop
in stifles or hocks in limbs treated with triple pelvic
osteotomy.

a
AMTI OR6-3A force plate; Advanced Mechanical Technology, Inc., New-
ton, MA
b
Data translation 2801-A analog digital converses; Data Translation, Inc.,
Marborough, MA
c
Zenith model 248 personal computer; Zenith Data Systems Corp., Inc., St.
Joseph, MI
d
Canine pelvic osteotomy plate; Slocum Enterprises, Eugene, OR

Acknowledgments
Funding provided in part by the American Animal
Hospital Association.

References
1. Hohn RB, Janes JM. Pelvic osteotomy in the treatment of canine hip
dysplasia. Clin Orthop Rel Res 1969;62:70–8.
2. Schrader SC. Triple osteotomy of the pelvis as a treatment for canine hip
dysplasia. J Am Vet Med Assoc 1981;178:39–44.
3. Schrader SC. Triple osteotomy of the pelvis and trochanteric osteotomy
as a treatment for hip dysplasia in the immature dog: the surgical
technique and results of 77 consecutive operations. J Am Vet Med Assoc
1986;189:659–65.
4. Slocum B, Devine T. Pelvic osteotomy technique for axial rotation of the
acetabular segment in dogs. J Am Anim Hosp Assoc 1986;22:331–8.
5. Slocum B, Devine T. Pelvic osteotomy in the dog as treatment for hip
dysplasia. Sem Vet Med Surg (Sm Anim) 1987;2:107–16.
6. Slocum B, Slocum T. Pelvic osteotomy. Vet Clin N Am (Sm Anim)
1992;22:645–82.
7. Dejardin LM, Perry RL, Arnoczky SP, Torzilli PA. The effect of triple
pelvic osteotomy on hip force in dysplastic dogs: a theoretical analysis.
Vet Surg 1996;25:114–20.