Multilobular Osteochondrosarcoma in

39 Dogs: 1979–1993

Thirty-nine, older, large-breed dogs with multilobular osteochondrosarcoma (MLO)

each presented primarily with a fixed mass involving the flat bones of the skull.
Twenty-five dogs were treated with surgical resection alone, nine were treated with
adjuvant therapy, and five were not treated. Forty-seven percent of dogs treated had
local tumor recurrence, and 56% had metastasis. Median time to recurrence, median
time to metastasis, and median survival time were 797, 542, and 797 days,
respectively. Histological grade, surgical margins, and tumor location affected
outcome. Long-term remission can be obtained with aggressive treatment of MLO,
although it is locally invasive and moderately metastatic.
J Am Anim Hosp Assoc 1998;34:11–8.

William S. Dernell, DVM, MS Introduction

Rodney C. Straw, BVSc
Mary F. Cooper, DVM
Barbara E. Powers, DVM, PhD
Susan M. LaRue, DVM, PhD
Stephen J. Withrow, DVM
RS
From the Comparative Oncology Unit,
Department of Veterinary Clinical
Sciences (Dernell, Straw, Cooper,
Withrow), and the
Departments of Pathology (Powers) and
Radiologic Health Sciences (LaRue),
College of Veterinary Medicine and
Biomedical Sciences,
Colorado State University,
Fort Collins, Colorado 80523.
Multilobular osteochondrosarcoma (MLO) is an uncommon tumor of
the flat bones of the canine skull, with rare reports of sites other than
the skull. The clinical presentation is that of a firm, fixed mass.
Neurological signs can occur, depending on location and invasive-
ness of the lesion.1 Multilobular osteochondrosarcoma is typically a
slow-growing, locally invasive, malignant neoplasm which often re-
curs after marginal excision. 1 Although some authors have reported
rare metastases, 1–3 a recent report has shown a more variable meta-
static pattern.4
Radiographically, MLO appears as a mass with nodular or stippled
mineralized densities, giving a “popcorn ball” appearance [Figure 1].
Lysis of underlying bone frequently is present.5 Grossly, the tumor is
a firm, gritty, grayish white-to-yellow, nodular mass with occasional
areas of necrosis 1,6 [Figure 2]. Histologically, the tumor appears as a
multilobular mass, with the lobules demarcated by fibrovascular septa.
A characteristic trilaminar appearance to the nodules is present, con-
sisting of a central area of cartilage or bone that may be calcified or
ossified; a middle zone of plump, spindle- to ovoid-shaped cells; and
a peripheral zone of fibrous tissue [Figure 3]. 1,4 Although the bony
margins may be invaded by the tumor, the surrounding soft tissue
often is compressed rather than infiltrated by the mass.
Multilobular osteochondrosarcoma occurs primarily in older, me-
dium- to large-breed dogs, but has been reported in young7 and small
dogs. 8,9 The tumor has been reported in humans, 10,11 cats,12 a horse,13
and a ferret.14 Synonymous terms include chondroma rodens, carti-
lage analogue of fibromatosis, calcifying aponeurotic fibroma, juve-
nile aponeurotic fibroma, multilobular osteoma, multilobular
chondroma, multilobular tumor of bone,1 and multilobular osteosarcoma.6
Numerous case reports describing MLO appear in the veterinary
literature.2,3,5,8,9,15–19 The purpose of the present report is to describe
the clinical and pathological manifestations as well as the treatment
and outcome in a large number of dogs with MLO treated at a single
institution.

JOURNAL of the American Animal Hospital Association 11

12 JOURNAL of the American Animal Hospital Association January/February 1998, Vol. 34

Figure 1—Radiograph of a resected multilobular osteochondro- Figure 2—Photograph of a resected multilobular osteochondro-
sarcoma from the maxilla, demonstrating the typical “popcorn sarcoma showing the typical gross appearance on cut surface.
ball” appearance of the tumor.

Materials and Methods

Case Selection and Evaluation

Records of all cases presented to the Clinical Oncol-
ogy Service, College of Veterinary Medicine, Colo-
rado State University (CSU) from January 1979
through December 1993 with a diagnosis of MLO
were reviewed. Cases were selected if there was his-
tological confirmation of MLO with histological
slides available for review and adequate recorded in-
formation to assess case presentation, treatment, and
response. Case information included breed, sex, age,
Figure 3—Photomicrograph of a multilobular osteochondrosar-
weight, treatment history, clinical presentation, pre- coma demonstrating multiple lobules, each consisting of cen-
operative evaluation, surgical management and resec- tral cartilaginous or bone matrix surrounded by a thin layer of
tion margins, adjuvant therapy including external spindle cells (Hematoxylin and eosin stain, 100X).
beam radiotherapy or chemotherapy, pathological
grade, clinical outcome, and necropsy findings. necropsies were performed to include gross examina-
Cases were followed by presentation to CSU or by tion of all body systems and the primary disease sites.
conversations with referring veterinarians or owners. Histological samples were obtained for confirmation
Owners were encouraged to present their animals for of metastasis and local recurrence. When necessary,
follow-up physical examinations and thoracic radio- samples were decalcified in formic acid within an
graphic evaluations one, three, six, nine, and 12 ion-exchange resin, dehydrated, and then embedded
months following initial treatment. When permitted, in paraffin. Sections (6 to 7 µm) were cut, mounted
January/February 1998, Vol. 34 Multilobular Osteochondrosarcoma 13

dog were harvested by centrifugation of whole blood

Appendix through a filter system b with a density of 1.077. Lym-
Histological Grading Criteria for phocytes then were counted and used as diploid stan-
Multilobular Osteochondrosarcoma dards. For each diploid index (DI) determination,
three tubes (i.e., tumor alone, lymphocytes alone, and
Criteria Score tumor and lymphocytes combined) containing ap-
proximately two million cells each were prepared.
Borders
Cells were fixed in 50% ethanol in citric acid-buff-
Pushing 1
ered saline, then stained with 50 µg/ml of propidium
Pushing and invasive 2 iodide c and analyzed using flow cytometry. Flow
Invasive 3 cytometry was performed on a commercial flow cyto-
Size of lobules meterd or on a flow cytometer constructed at CSU.21
Small and medium 1 Procedures for flow cytometry have been described
Large 2 in detail previously.20
Organization
Well organized 1
Statistical Evaluation
Moderately well organized 2 Time (in days) to local recurrence was calculated
Poorly organized 3 from the date of initial surgery to the date of clinical,
radiographic, or histological evidence of recurrence.
Mitotic figures/10 HPFs*
For cases in which a second surgery was performed to
1 to 5 1
remove recurrent disease, a second time to recurrence
6 to 10 2
was calculated from the date of the second surgery to
>10 3 the time of additional recurrence. All recurrence times
Pleomorphism of cells were included in the analysis. Time (in days) to me-
Monormorphic 0 tastasis was calculated from the time of initial diag-
Mild 1 nosis to the time of clinical, radiographic, or
Moderate 2 histological evidence of metastatic disease. Survival
Marked 3 times (in days) were calculated from the time of
Necrosis initial evaluation to the time of death or loss to
None 0 follow-up.
Present 1 A multifactorial analysis was performed using a
Cox proportional hazards model for the influence of
Grade Total
various factors on time to local recurrence, time to
Grade I 7 or less
metastasis, and survival times. Factors evaluated in-
Grade II 8 to 12
cluded tumor grade (i.e., I, II, or III); surgical mar-
Grade III 13 or greater gins (i.e., complete or incomplete); tumor diameter
* HPFs=high-powered fields (i.e., 4 cm or less; 5 cm or greater); tumor location
(i.e., mandible or other skull site); number of surgical
procedures performed; previous resection (prior to
presentation to CSU); whether animals were treated
on slides, and stained with hematoxylin and eosin with surgery alone or a combination of surgery and
stain. All histology samples were reviewed by one adjuvant therapy; whether a preoperative computed
pathologist (Powers) and were scored using the sys- tomography (CT) scan was performed; and flow
tem described by Straw, et al. 4 [see Appendix]. cytometry results (i.e., diploid or nondiploid). Kaplan-
Meier product limit method was used to evaluate me-
Flow Cytometry dian local recurrence, metastasis, and survival times.
Flow cytometry was performed to determine diploid Cases that did not show local recurrence, that did not
or nondiploid status on nine cases. Samples were show metastasis, or that died of a nontumor or tumor-
obtained at the time of tumor excision. A 1-cm 3 sec- related cause or were lost to follow-up were cen-
tion of tumor was removed prior to formalin fixation sored from the evaluation for time to local
for histological processing and evaluation. Single- recurrence, time to metastasis, and survival time,
cell suspensions for flow cytometric evaluation were respectively. Cases that were not treated also were
obtained by coarsely mincing the sample, followed excluded from the analysis. Pearson’s product-mo-
by mechanical disaggregation in phosphate-buffered ment correlation coefficients were used to evalu-
saline in a mechanical digestera as described previ- ate the relationship between flow cytometry results
ously. 20 Lymphocytes from the patient or a normal and tumor grade.
14 JOURNAL of the American Animal Hospital Association
Results
Thirty-nine cases were found to meet the study crite-
ria. Twelve of the cases included were presented in a
previous article. 4 The study population consisted of
16 ovariohysterectomized females, 11 castrated males,
nine intact males, and three intact females. The
male:female ratio was 1.05. Eighteen breeds were
represented, consisting of mixed-breed dogs (n=13),
golden retrievers (n=4), Labrador retrievers (n=4),
Doberman pinschers (n=3), German shepherd dogs
(n=2), and one each of the English bulldog, Great
Dane, English setter, Old English sheepdog, rott-
weiler, basset hound, English springer spaniel, chow
chow, collie, Siberian husky, Finnish spitz, Irish wolf-
hound, and standard schnauzer breeds. Median age
was eight years (range, four to 17 years). Median
weight was 29 kg (range, 8.2 to 69.4 kg).
Tumors involved the maxilla (n=11), mandible
(n=10), calvarium (n=14), orbit (n=1), tympanic bulla
(n=1), both the orbit and maxilla (n=1), and both the
zygoma and the maxilla (n=1). Median diameter was
4 cm (range, 1 to 11 cm). The presenting complaints
were a firm, fixed mass (n=21; 54%); swelling (n=4);
neurological signs (n=2); ocular signs, weight loss,
dyspnea, or pain in one case each; both a mass and
exopthalmus (n=4); pain and exopthalmus (n=2); and
a mass and pain (n=1).
Five cases were not treated. Thirty-four cases were
treated, with four of these undergoing additional treat-
ments for local recurrence, for a total of 38 tumors
treated. Twenty-five cases were treated with surgery
alone, three of which underwent surgical resection of
the primary lesion and a recurrent lesion at a later
date. Nine of the resections were performed for lo-
cally recurrent masses after previous resections by
referring veterinarians. Thirty-seven surgeries were
performed, including maxillectomies (n=11), man-
dibulectomies (n=12), orbitectomies (n=2), partial
craniectomies (n=4), and combination surgeries (n=8),
all with the intent of complete resection. Adjuvant
therapy was performed in nine cases (10 tumors) when
complete resection was not possible, either from a
preoperative or postoperative assessment or follow-
ing histological indication of incomplete resection.
Following surgical resection, six cases were implanted
with a biodegradable polymer (open cell polylactic
acid) containing cisplatin (OPLA-Pt)22 (34 to 60 mg/m2)
within the surgical field. One case was implanted a
second time (60 mg/m 2) following tumor recurrence.
One of these six cases also was given external beam
radiation therapy at 49.5 Gy (15 fractions of 3.3 Gy).
One case was treated with adjuvant intraoperative
radiation therapy at 20 Gy (single dose). Two cases
were treated with adjuvant external beam radiation in
combination with intravenous (IV) cisplatin. One of
January/February 1998, Vol. 34
these cases was given 48 Gy (16 fractions of 3 Gy)
and one IV dose of cisplatin (70 mg/m 2). The other
case was treated with 49 Gy (15 fractions of 3.3 Gy)
combined with four IV doses of cisplatin at 70 mg/m2.
Of the 37 surgeries performed, surgical margin
evaluation was recorded in 32 cases. In 19 cases,
margins were considered complete, and in 13 cases
they were considered incomplete. Thirteen tumors
were classified as grade I, 17 were classified as grade
II, and nine were classified as grade III.
Of the five untreated cases, three are dead from
their disease (two with local disease only and one
with local disease and metastasis). One case died due
to a concomitant chondrosarcoma of the pelvis with
lung metastases, and one case was lost to follow-up
with local disease present at 350 days. Median sur-
vival time for this group was 24 days (range, two to
530 days).
Of the 34 treated cases, 19 are dead from their
disease (five with local recurrence, five with me-
tastases, and nine with both local recurrence and me-
tastases). Eleven cases (including one case with local
recurrence and one case with metastasis) are dead due
to other causes. One case is alive with no evidence of
disease at 2,340 days. Three cases were lost to fol-
low-up, all with no evidence of disease, at 394, 720,
and 1,332 days.
Of the 38 tumors treated, 18 (47%) developed lo-
cal recurrence. Median time to local recurrence was
797 days (range, 30 to 1,332 days). Nineteen (56%)
of 34 cases treated developed metastasis. Median time
to metastasis was 542 days (range, zero to 1,225 days).
Four cases had metastasis at the time of presentation.
Clinically evident metastasis was primarily to the
lungs (90%). Metastatic sites confirmed by necropsy
included the lung (n=4); the lung and soft tissue (n=1);
and the lung, soft tissue, and long bone (n=1). Histol-
ogy of metastatic and recurrent lesions was similar to
the primary site. Six (33%) of 18 cases which devel-
oped recurrence subsequently developed metastases.
The effect of local recurrence on the development of
metastasis was not found to be significant. Of six
cases treated with adjuvant chemotherapy, three de-
veloped local recurrence and one developed both lo-
cal recurrence and metastasis. Three of these cases
had metastasis at the time of initial treatment. Of two
cases treated with adjuvant radiation therapy, one
developed local recurrence and one developed local
recurrence and metastatic disease. The two cases
treated with both adjuvant chemotherapy and radia-
tion therapy developed local recurrence and meta-
static disease. Median survival time for the cases of
this report was 797 days (range, 28 to 1,670 days).
Median time to death from the onset of recurrent or
metastatic disease was 239 days (range, two to 1,280
days).
January/February 1998, Vol. 34
Figure 4—Kaplan-Meier survival curve showing a significant
negative effect on time to local recurrence for (1) incomplete
surgical margins compared with (2) complete margins.
Multifactorial analysis revealed a significant ef-
fect for margin evaluation on time to local recurrence
with a hazard ratio of 11.05 and 95% confidence
interval of 1.549 to 78.78 (p of 0.017). Median time
to local recurrence for complete margins was not
reached at 1,332 days (range, 165 to 1,332 days),
with eight (42%) of 19 cases having recurrence. Me-
dian time to local recurrence for incomplete margins
was 320 days (range, 30 to 782 days), with 10 (77%)
of 13 cases having recurrence [Figure 4]. High tumor
grade (grade III) also was shown to have a significant
negative effect on time to local recurrence, with a
hazard ratio of 21.2 and 95% confidence interval of
1.110 to 405.1 (p of 0.042). Seven (78%) of nine grade
III tumors, seven (47%) of 15 grade II tumors, and three
(30%) of 10 grade I tumors had local recurrence.
An effect also was found for tumor grade on time
to metastasis, with grade II (p of 0.030) and III (p of
0.007) tumors having significantly lower times to
metastasis and hazard ratios of 29.33 and 194.5, re-
spectively, and 95% confidence interval of 1.324 to
649.8 and 4.227 to 8,947, respectively. Median times
to local recurrence, times to metastasis, and survival
times based on tumor grade are listed in the Table.
Seven (78%) of nine grade III tumors, nine (60%) of
15 grade II tumors, and three (30%) of 10 grade I
tumors metastasized.
A significant effect was found for survival time
based on tumor location favoring mandibular sites
with a hazard ratio of 12.39 and 95% confidence
interval of 1.59 to 96.56 (p of 0.016). Median sur-
vival time for mandibular tumor sites was 1,487 days
compared to 528 days for nonmandibular tumor sites
(i.e., maxilla, calvarium, orbit).
Of the nine cases in which flow cytometry was
performed, five were found to be diploid and four
were found to be nondiploid. Of diploid tumors, three
were grade III, and one each were grade II and I. All
nondiploid tumors were grade II. The correlation co-
efficient between flow cytometry results and tumor
Multilobular Osteochondrosarcoma 15
grade was 0.31. There were no significant effects of
flow cytometry results on time to local recurrence,
time to metastasis, or survival time.
Discussion
Signalment in the present study was consistent with
that of the previous review 4 and with previous case
reports. 2,3,18,19,23,24 Multilobular osteochondrosarcoma
appears to be a disease of middle-aged to older, me-
dium- to large-breed dogs, although reports of young
and small 8,9 dogs 7 exist. In this study, median weight
was 29 kg, although four dogs weighed less than 25
kg. No breed or sex predilection was noted.
Tumors were located primarily in the flat bones of
the skull. It has been proposed that the characteristic
multilobular pattern of the tumor is attributable to
abnormal cellular activity arising from the perios-
teum of bones formed by intramembranous ossifica-
tion. 1 The fact that all bones of the skeleton arise, in
part, from intramembranous ossification has led to
debate of this theory to explain the preferential skull
sites for MLO. 4,25 Another attempt to explain the pref-
erential skull sites revolves around the theory that
MLO cells may arise from periosteal cells of only
chondrocranium and viscerocranium, which share
common embryological sites.2
Presenting signs were similar to previous reports,
with the presence of a mass or swelling being most
common. 3,4,8,9,23,24 Neurological2,4 and ocular4,18 signs
also occurred, dependent on tumor location. The rela-
tively slow and nonaggressive, local, biological be-
havior of this tumor (compared to high-grade
osteosarcoma) probably allows it to grow to medium-
to-large size prior to causing clinical signs. The ten-
dency for MLO to compress adjacent structures rather
than invade probably results in the slow development
of neurological signs which do not occur until central
nervous system structures are compromised from pres-
sure. 1 Size was not found to have a significant effect
on recurrence, metastasis, or survival in the present
study. It would seem logical that larger tumors may
be more likely to predispose to local recurrence due
to the increased difficulty of complete resection. It
may be that anatomic location is a more pivotal
factor in dictating completeness of resection than
size.
Incomplete surgical margins were found to be sig-
nificant in decreasing the time to local recurrence.
The hazard ratio would indicate that incomplete sur-
gical margins would have an approximate 11-fold
increased chance of significantly shorter time to local
recurrence compared to complete surgical margins.
Previous case reports have shown a tendency for tu-
mor recurrence following marginal resection.3,4,8,18
The Cox proportional hazards ratio in this study indi-
cates that nonmandibular sites have an approximate
16 JOURNAL of the American Animal Hospital Association
Table
Survival Outcome for Multilobular Osteochondrosarcoma Based on Tumor Grade
Grade I II
Number of cases 13
Time to local recurrence
(days)
Median >1,332
Range 192–1,332
Time to metastasis
(days)
Median >820
Range 720–820
Survival time
(days)
Median >897
Range 66–797
12-fold increased chance of significantly decreased
survival when compared to mandibular sites. This
merely may be a reflection of the better ability to
resect mandibular masses adequately with aggressive
mandibulectomy procedures.
Median time to local recurrence was over two years
in the present study, which was longer than the times
to local recurrence in the previous review and several
case reports. 2–4,8,18,23 Since surgical margins appear
to play an important role in local tumor control with
MLO, it might be expected that advanced imaging
would help in preplanning resection margins accu-
rately, especially with the typical skull locations of
this tumor. Cases evaluated preoperatively with CT
in the present study did not show improved local or
distant disease control; however, CT was utilized in a
small number of cases, and selection bias may have
existed, with CT chosen for more difficult (i.e., re-
section) cases. Further evaluation of imaging modali-
ties and their influence on outcome for MLO is
warranted. The number of surgical resections was not
found to have a significant effect on time to local
recurrence, time to metastasis, or survival time. This
would support the slow, insidious, local behavior of
this tumor and the primary influence of surgical mar-
gins regardless of the number of resections. In the
previous review, 75% of dogs that developed local
recurrences subsequently developed metastatic dis-
ease.4 This effect was not found to be significant (p of
0.055) in the present study, although a trend may be
evident.
Increasing tumor grade was related to decreased
time to local recurrence, time to metastasis, and sur-
vival time for the present study [see Table], indicating a
relationship between more aggressive histological fea-
January/February 1998, Vol. 34
III
17 9
782 288
30–782 82–534
405 321
28–1,225 150–542
520 405
28–1,487 82–1,670
tures and more aggressive biological behavior. A
grade III MLO would have an approximate 21-fold
increased chance of significantly shorter time to local
recurrence and a 195-fold increased chance of sig-
nificantly shorter time to metastasis compared to a
grade I tumor based on the hazard ratios. Grading of
MLO is not a common finding in pathological reports
in the veterinary literature and was not established
until the previous review. 4 Tumor grade has been
shown to be predictive of biological behavior for a
variety of tumors in animals 26 and humans.27
Greater than 50% of the dogs in the present study
developed metastases. Previous case reports have de-
scribed metastasis. 2,3 However, some reports have
considered this tumor type to have a low metastatic
rate 1–3,8 rather than a more moderate rate which was
indicated by this and the previous study. 4 Time to
local recurrence, time to metastasis, and survival time
were long when compared to the more common pri-
mary bone tumor, osteosarcoma. A median survival
time of 239 days (range, two to 1,280 days) from the
onset of locally recurrent or metastatic disease would
support a relatively slow biological behavior com-
pared to other malignant bone tumors. 1 Median sur-
vival time for the four cases presented with metastases
and subsequently treated for their local disease was
420 days, which also supports the relatively slow
biological behavior of MLO. Of these four cases, two
each had grade I and grade II tumors, which may
indicate a grade influence on the prolonged survival
times of these dogs. In a recent study, dogs with
solitary (or few), slow-growing, pulmonary, meta-
static osteosarcoma lesions (which were more than
365 days out from the start of their treatment) showed
significant improvement in survival times following
January/February 1998, Vol. 34
pulmonary metastasectomy when compared to those
dogs not undergoing metastasectomy. 28 Pulmonary
metastasectomy may be beneficial in MLO cases, es-
pecially those cases with lower grade tumors.
A high percentage of dogs receiving adjuvant
therapy subsequently developed local recurrence or
metastasis or both in the present study. This may be a
reflection of the clinical selection of adjuvant thera-
pies in high-risk cases. The effect of adjuvant thera-
pies on control of MLO disease was not shown to be
significant when compared to surgery alone. Com-
parisons are difficult, however, due to the extreme
variability in treatment among these cases. Adjuvant
therapies generally were chosen for the worst cases,
which may have resulted in a selection bias. The use
of OPLA-Pt was based generally on the inability to
obtain complete margins when resecting the primary
mass. It did not appear, from the small number of
cases in this report, that this therapy had a benefit in
controlling MLO disease. This form of intracavitary
cisplatin chemotherapy has been shown to decrease
significantly the local recurrence rates in cases of
marginal resection for osteosarcoma. 22 The previous
review also failed to show an appreciable effect for
improving outcome by the use of adjuvant therapy.4
The role of chemotherapy and radiation therapy for
MLO requires further investigation in more controlled
studies. Two previous case reports described radia-
tion therapy adjunctive to surgery in cases of MLO
which recurred six and nine months after therapy. 3,18
Flow cytometry was not shown to be predictive of
treatment outcome in this study, nor was it shown to
correlate with tumor grade. However, it is difficult to
draw conclusions due to the small number of dogs
evaluated. Flow cytometry has been shown to be pre-
dictive of outcome for chondrosarcoma in humans
with diploid tumors, having significantly better out-
come than aneuploid tumors. 29 Further evaluation of
flow cytometry in a larger number of MLO cases may
be warranted.
Conclusion
Multilobular osteochondrosarcoma occurs as a
firm, fixed mass originating from the flat bones of
the skull primarily in medium- to large-breed dogs.
It is a slow-growing, locally invasive tumor with
moderate metastatic potential, with histological
grade being prognostic in that higher grades show
more aggressive biological behavior. Aggressive
surgical resection, if it results in complete mar-
gins, can result in long-term disease remission.
The effectiveness of adjunctive therapy in cases of
MLO has not been demonstrated.
a bone tumors in the dog. J Sm Anim Pract 1977;18:313–26.
Stomacher; VWR Corporation, Denver, CO
b
Histopaque; Sigma Chemical Company, St. Louis, MO
Multilobular Osteochondrosarcoma 17
c
PI; CalBioChem, San Diego, CA
d
EPICS V; Coulter Corporation, Hialeah, FL
Acknowledgments
Supported in part by grant no. 2 PO1 CA 29582 from
the National Cancer Institute. Contents are solely the
responsibility of the authors and do not necessarily
represent the official views of the National Cancer
Institute.
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21. Fox MH, Coulter JR. Enhanced light collection in a flow cytometer.
Cytometry 1980;1:21–5.
22. Withrow SJ, Straw RC, Dernell WS. Local slow release cisplatin after
limb sparing or amputation for canine osteosarcoma. Florence, Italy:
Proceed, European Musculo-Skeletal Oncology Soc, 1995:35 (abstract).
23. Liu SK, Dorfman HD. The cartilage analogue of fibromatosis (juvenile
aponeurotic fibroma) in dogs. Vet Path 1974;11:60–7.
24. Liu SK, Dorfman HD, Hurvitz AI, Patnaik AK. Primary and secondary
(Continued on next page)
18 JOURNAL of the American Animal Hospital Association January/February 1998, Vol. 34

References (cont’d)
25. Withrow SJ, Holmberg DL. Mandibulectomy in the treatment of oral
cancer. J Am Anim Hosp Assoc 1983;19:273–86.
26. Powers BE. The pathology of neoplasia. In: Withrow SJ, MacEwen EG,
eds. Small animal clinical oncology. Philadelphia: WB Saunders, 1996:
4–15.
27. Diamanti L, Montironi R, Prete E. Up-date on quantitative grading
systems and prognosis. Anticancer Res 1994;14:1297–304.
28. O’Brien MG, Straw RC, Withrow SJ, et al. Resection of pulmonary
metastases in canine osteosarcoma: 36 cases (1983–1992). Vet Surg
1993;22:105–9.
29. Adler CP, Herget GW, Neuburger M. Cartilaginous tumors: prognostic
applications of cytophotometric DNA analysis. Cancer 1995;76:
1176–80.
 Clinical Features of Trigeminal
Nerve-Sheath Tumor in 10 Dogs
Nerve-sheath tumor was diagnosed in 10 dogs with clinical signs of unilateral
trigeminal nerve dysfunction. Unilateral temporalis and masseter muscle atrophy
were present in all cases. An enlarged foramen and distorted rostral petrous
temporal bone were seen with computed tomography imaging in one case. Magnetic
resonance imaging was used to identify the lesion accurately in seven cases.
Surgery was performed for biopsy and lesion removal in three cases. Cases not
treated had a progressive course eventually resulting in euthanasia or death. Of the
cases treated surgically, one case is alive without disease progression 27 months
after surgery. Survival times of the nontreated cases ranged from five to 21 months.
J Am Anim Hosp Assoc 1998;34:19–25.

Rodney S. Bagley, DVM Introduction

Simon J. Wheeler, BVSc, PhD
Lisa Klopp, DVM
Donald C. Sorjonen, DVM, MS
William B. Thomas, DVM, MS
Brent E. Wilkens, DVM
Patrick R. Gavin, DVM, PhD
Ruth Dennis, MA, Vet MB
RS
From the Department of
Clinical Sciences (Bagley, Gavin),
College of Veterinary Medicine,
Washington State University,
Pullman, Washington 99164-6610; the
Department of Small Animal Medicine
and Surgery (Wheeler),
the Royal Veterinary College,
London, United Kingdom; the
Department of Small Animal Surgery
and Medicine (Klopp, Sorjonen),
College of Veterinary Medicine,
Auburn University,
Auburn, Alabama 36849; the
Department of Small Animal
Clinical Sciences (Thomas, Wilkens),
College of Veterinary Medicine,
University of Tennessee,
Knoxville, Tennessee 37901-1071; and
the Animal Health Trust (Dennis),
Newmarket, United Kingdom.
The trigeminal nerve supplies afferent sensory information from the
head and face and efferent motor innervation to the muscles of masti-
cation. The name of this cranial nerve is derived from the Latin
“trigeminus,” meaning three born at the same time. 1 This description
reflects the fact that this nerve has three main branches: the oph-
thalmic nerve, maxillary nerve, and mandibular nerve. The ophthalmic
branch is sensory to the eye and surrounding skin. The maxillary
branch supplies sensory innervation to the maxillary area. The man-
dibular branch supplies sensory innervation to the mandibular area of
the face and motor innervation to the muscles of mastication.
Disease processes selectively involving this nerve are rare. Of
these, neoplastic involvement is surprisingly common.2–11 While
trigeminal nerve involvement with myelomonocytic leukemia and
lymphosarcoma is reported,12,13 nerve-sheath tumors are present more
frequently.2–11 Clinical features, results of diagnostic tests, and treat-
ments of these latter tumors, however, often are lacking. In this
report, 10 dogs with unilateral trigeminal nerve dysfunction each
were found to have a nerve-sheath neoplasm. Clinical signs and
imaging features of 10 affected cases, including surgical treatment of
three cases, are reported. Clinical features of case no. 9 have been
described previously.14
Case Reports
No breed predilection was identified among the 10 cases affected [see
Table]. Age of cases at admission ranged from four to 14 years
(median, eight years). Six cases were male, two were intact female,
and two were neutered females.
Duration of clinical signs prior to admission ranged from five days
to 18 months (median duration, five months). Clinical signs reflected
unilateral trigeminal nerve dysfunction. Six cases had tumors of the
left trigeminal nerve, and four cases had tumors of the right trigemi-
nal nerve. All cases had ipsilateral atrophy of the temporalis and
masseter muscle groups. Other clinical signs, in order of decreasing
frequency, included reduced facial sensation (n=5), absent palpebral
reflex with normal menace response (n=3), reduced corneal sensation

JOURNAL of the American Animal Hospital Association 19

20 JOURNAL of the American Animal Hospital Association
Table
Characteristics of Dogs with Trigeminal Tumors
Case Age
No. Breed Sex* (yrs)
1 Rottweiler M 4
2 Whippet FS 13
3 German shepherd dog M 14
4 Beagle M 8
5 American Staffordshire terrier M 8.5
6 Miniature schnauzer FS 7 Surgery/
7 Labrador retriever M 8
8 Boxer M 7
9 Jack Russell terrier F 8
10 Bernese mountain dog F 5.5
* M=male; FS=spayed female; F=female
and corneal ulcer (n=3), rubbing of the face (n=3),
decreased menace response (n=1), torticollis (n=1),
ipsilateral Horner’s syndrome (n=1), and ptosis (n=1).
One case had ipsilateral hemiparesis at presentation,
and two other cases developed hemiparesis during the
courses of their disease. One case developed signs of
forebrain disease ipsilateral to the tumor. Abnormali-
ties in this case included a contralateral menace defi-
cit associated with decreased vision, normal palpebral
reflex, and normal pupillary light reflex; contralateral
hemiparesis; and contralateral facial sensation
deficits. An additional case had severe ataxia at
presentation.
Fibrillation potentials and positive sharp waves
were present upon electromyography of the temporalis
and masseter muscles in each of five cases examined.
Three cases had cerebrospinal fluid (CSF) collected
from the cerebellomedullary cistern; protein content
of the CSF was elevated (27 mg/dl, 37 mg/dl, and 101
mg/dl, respectively; reference range, less than 25 mg/dl).
One case had concurrent mononuclear pleocytosis (30
nucleated cells/µl; reference range, less than 5 nucle-
ated cells/µl). Two cases had normal nucleated cell counts.
Three cases had computed tomography (CT) per-
formed. One of these studies was inconclusive; the
other two each had an isodense lesion that was en-
hanced with intravenous contrast mediuma adminis-
tration. In one case, the rostral part of the petrous
temporal bone in the area of the trigeminal canal had
a distorted and enlarged oval foramen on the ventral
surface of the skull [Figures 1A, 1B].
January/February 1998, Vol. 34
Treatment Outcome
Surgery Alive 27 months after surgery
None Died in hospital
None Euthanized at presentation
None Euthanized
None Alive 11 months after diagnosis
Euthanized due to progressive
retrovirus disease five months after surgery
injection
Surgery Alive five months after surgery
None Euthanized 21 months after onset
of clinical signs
None Euthanized 11 months after onset
of clinical signs
None Euthanized 13 months after onset
of clinical signs
Magnetic resonance (MR) imaging was performed
in seven cases. Three of these cases had previous CT
imaging. With MR imaging, an extra-axial mass was
seen in either the middle or caudal fossa [Figures 2A,
2B]. While imaging characteristics varied, the major-
ity of the lesions were isointense on T1-weighted
images and either isointense or hyperintense on T2-
weighted images. All lesions had mixed isointense
and hyperintense patterns on proton density-weighted
images. Enhancement of the lesions was noted for all
cases following intravenous administration of con-
trast material. b In three cases, the mass distorted the
associated brain stem.
Two cases were euthanized or died soon after ad-
mission to the hospital, and necropsy and histopa-
thology were performed [Figures 3A, 3B, 3C]. Four
cases were euthanized due to disease progression
without definitive treatment. Survival times after pre-
sumptive diagnoses of these four cases ranged from
five to 21 months (median survival time, 12 months).
One case was diagnosed presumptively without histo-
pathological diagnosis based upon clinical and radio-
graphic features. 14 Owners elected for no additional
treatment. Diagnoses were made in three cases from
surgical biopsies.
Definitive diagnoses were made in nine cases based
on histopathological examination of affected tissue.
Histological features were consistent with those cri-
teria for diagnosis of a nerve-sheath neoplasm.2–11
Predominant histological features consisted of
spindle-shaped cells connected in interlacing bundles.
January/February 1998, Vol. 34
Figure 1A
Figure 1B
Figures 1A, 1B—(A) Computed tomographic view set to en-
hance bone (bone window). Note the distortion of the rostral
petrous temporal bone (arrow). (B) Computed tomographic view
taken at a level 5 mm rostral to that of Figure 1A. Note the
enlarged cranial foramen (arrow).
Neurons often were seen incorporated in the lesion
[Figure 3C]. Three tumors were diagnosed as neurofi-
brosarcomas, one as a schwannoma and the remain-
ing five as unclassified nerve-sheath neoplasms.
In the three cases (case nos. 1, 6, 7) having sur-
gery, a lateral rostrotentorial craniectomy (n=1; case
no. 1) or a transzygomatic craniectomy (n=2; case
nos. 6, 7) was performed to provide exposure of the
ventral and ipsilateral floors of the skull. The lateral
rostrotentorial craniectomy performed in case no. 1 is
described as an example of the surgical procedures.
The mass was approached surgically via a left
rostrotentorial lateral craniectomy. The temporalis
Trigeminal Nerve Sheath Tumor 21
Figure 2A
Figure 2B
Figures 2A, 2B—(A) Noncontrast-enhanced and (B) contrast-
enhanced b T1-weighted magnetic resonance images of the
same case for which the computed tomographic view is shown
in Figures 1A, 1B. Note the mass (arrow) in the area of the
trigeminal nerve. Contrast enhancement is seen after intrave-
nous contrast administration.
muscle was atrophied, which was beneficial during
ventral exposure as the atrophied muscle could be
retracted easily. The craniectomy was extended ven-
trally to the level of the caudal attachment of the
zygomatic arch. Upon exploration just lateral and
rostral to the level of the attachment of the zygomatic
arch, a firm, rounded structure (assumed to be nerve)
was identified. This structure was traced medially to
the level at which it entered the skull through a fora-
men. A high-speed air drill was used to enlarge the
foramen medially and caudally, following the path of
22 JOURNAL of the American Animal Hospital Association
Figure 3A
Figure 3B
Figures 3A, 3B, 3C—(A) Lateral and (B) dorsoventral views of
the brain at necropsy of a dog with a trigeminal nerve-sheath
tumor. Note the enlarged, discolored lesion involving the left
trigeminal nerve (arrows). (C) Photomicrograph of a trigeminal
nerve-sheath tumor (original magnification, 100X). Neurons
(arrows) are entrapped by spindle-shaped neoplastic cells.
the nerve. The left temporal lobe was retracted dor-
sally to allow additional exposure of the ventral as-
pect of the calvarium. The dura overlying this area
January/February 1998, Vol. 34
Figure 3C
was incised for better visualization. The mass was
traced medially into and through the trigeminal canal
to its point of entrance into the brain stem. Approxi-
mately 2 mm lateral to the brain stem, the nerve
appeared grossly normal. At this level, the nerve was
incised sharply and the mass was exteriorized. The
distal aspect of the mass extended slightly distal to
the foramen. Gross total resection was achieved.
Branches of the nerve were traced as far as possible
into the temporalis and masseter muscles and sharply
removed. After resection, a gel foam sponge c was
placed in the trigeminal canal to prevent hemorrhage.
The craniectomy incision was closed routinely.
Two grand mal, tonic clonic seizures occurred in
the immediate postoperative period. This was assumed
to be due to damage of the left temporal lobe result-
ing from tissue retraction. Phenobarbital (3 mg/kg
body weight, per os [PO] q 12 hrs) therapy was initi-
ated. No additional seizures were noted, and the phe-
nobarbital dosage was tapered and subsequently
discontinued at nine months after surgery.
In case nos. 6 and 7, the tumors were resected
subtotally and biopsied. In case no. 6, an initial sur-
gery was performed for lesion biopsy. At the time of
biopsy, a recombinant mouse retrovirus possessing a
herpes virus-thymidine kinase (HSV-TK) gene in a
fibroblast vector packaging cell line was injected into
the mass. Five days after this injection, ganciclovir
(GCV) (5 mg/kg body weight, intravenously [IV] q
12 hrs for five days) was given. A second surgery was
performed 15 days after the first for tumor debulking,
and the majority of the tumor was removed. A second
injection of HSV-TK was administered into the re-
maining tumor, followed in five days by a second
course of GCV therapy.
Acute postoperative abnormalities of the cases with
subtotal resection included ventromedial strabismus,
positional nystagmus, and hemiparesis. One of these
cases developed seizures after surgery which also
were treated with phenobarbital.
January/February 1998, Vol. 34
Figure 4A
Figures 4A, 4B—Rottweiler (case no. 1) with a trigmenial nerve
tumor (A) before and (B) after surgical resection of the tumor.
Note the unilateral temporalis muscle atrophy (A, arrow). (B)
Appearance of the dog one month after surgery. This dog is alive
more than 27 months after surgery.
Two cases (case nos. 1, 7) are alive 27 and four
months after surgery (at the time of submission of
this manuscript) [Figures 4A, 4B]. Further atrophy of
the temporalis and masseter muscles occurred in case
no. 1 which had the tumor removed en gross. The
atrophy has remained through the clinical course (27
months). Neurotropic keratitis and keratoconjunctivi-
tis sicca (KCS) occurred in the ipsilateral eye within
one month of surgery. These latter problems were not
significant clinically six months after surgery. Case
no. 6 had surgery and retrovirus injections; it initially
improved postoperatively, but eventually developed
dysphagia and trismus, and was euthanized five
months after surgery.
The additional case (case no. 5) that is alive and
did not have definitive therapy has had progressive
temporalis and masseter muscle atrophy. This dog
has a tendency to stumble and fall, possibly reflecting
progressive hemiparesis.
Discussion
Trigeminal nerve-sheath tumor is an uncommon in-
tracranial tumor in humans. 1,15–26 While the true inci-
dence of this tumor is unknown, estimates range from
Trigeminal Nerve Sheath Tumor 23
Figure 4B
0.07% to 0.36% of intracranial tumors. Onset of clini-
cal signs is usually in the fourth to fifth decade of
life. A variety of clinical signs are reported depend-
ing upon where the trigeminal nerve is affected. Many
humans complain of pain or altered sensation in the
area of the face innervated by the involved branches.
Sensory signs are more difficult to determine in dogs
since they are unable to verbalize these sensations to
the examiner. It is interesting, however, that facial
pain or dysesthesia was suspected in three of the
cases reported here. Other signs associated with oph-
thalmic nerve disease (e.g., neurotropic keratitis) and
mandibular nerve disease (e.g., masticatory muscle
weakness or atrophy) are less common in humans. In
this series of cases, however, unilateral atrophy of the
muscles of mastication was a dramatic and consistent
clinical feature. Clinical signs reflect dysfunction of
one or all of the branches of the nerve. Signs (e.g.,
hemiparesis, forebrain signs, Horner’s syndrome) of
dysfunction of other areas of the nervous system were
most likely the result of expansion of the mass and
subsequent damage to adjacent brain structures.
Unilateral masticatory muscle atrophy is uncom-
mon with myositis, and when present, a trigeminal
24 JOURNAL of the American Animal Hospital Association
nerve tumor should be suspected. Trigeminal neuri-
tis, a commonly diagnosed but poorly described dis-
ease, affects the mandibular branches of the nerve
bilaterally and is self-limiting.26 The other neoplastic
diseases that may affect the trigeminal nerves include
myelomonocytic leukemias and lymphosarcoma. 12,13
Electromyography may suggest denervation as a
cause of the atrophy, as evidenced by the presence of
fibrillation potentials and positive sharp waves noted
in all of five cases examined. Imaging studies allow
for examination of the ventral skull area and usually
are most helpful for diagnosis of a trigeminal tumor.
In humans, the appearance of trigeminal tumors var-
ies from hypo- to hyperdense on noncontrast, en-
hanced CT scans.16 Many of these tumors enhance
after IV contrast medium administration.
Many unilateral trigeminal tumors in humans are
well circumscribed, having decreased signal on T1-
weighted MR images and increased signal on T2-
weighted images. Other imaging modalities, such as
cavernous venography, usually are not as helpful as
CT and MR. Magnetic resonance imaging is the pre-
ferred diagnostic modality due to superior resolution
of the tumor boundary, direct imaging in the dorsal
plane, absence of beam-harding artifacts, and lack of
ionizing radiation.16
Differentiating nerve-sheath tumors as neurofib-
rosarcoma or schwannoma sometimes is difficult, as
designations used in humans for these tumors may
not always describe the lesions seen in animals.2,4,8,27
While some feel this type of discrete classification is
useful, the clinical behavior of these tumors is similar
regardless of further histological classification.2,4,8,27
In general, tumors of peripheral or cranial nerves,
whether designated as neurofibrosarcoma or
schwannoma, are invasive locally and slow to metas-
tasize. These tumors tend to infiltrate proximally into
the central neural axis, ultimately resulting in in-
creased morbidity and mortality. Local surgical re-
section is the preferred treatment for these tumors.
The efficacy of radiation therapy is variable; how-
ever, anecdotal evidence suggests that using radiation
therapy subsequent to local resection may improve
survival times. Interestingly, the authors have ob-
served distant metastasis in a few dogs with spinal
nerve-root tumors treated with radiation following
surgical resection. This suggests that improved local
control of nerve-sheath tumors may allow more time
for metastasis to become evident.
Surgical resection is of prime importance for con-
trol of intracranial trigeminal nerve-sheath tumor in
humans.17–22 Surgical approaches differ based upon
location of the majority of the tumor. A lateral
rostrotentorial craniectomy or transzygomatic craniec-
tomy was used in these cases to access the ventral
internal skull. The ipsilateral muscle atrophy was less
January/February 1998, Vol. 34
of a hindrance to surgical exposure of this region
compared to normal-sized temporalis muscle. Surgi-
cal morbidity (i.e., seizures) apparently was related
to brain retraction and brain stem manipulation for
tumor resection. Successful removal of the tumor was
achieved in one case, resulting in no additional long-
term neurological abnormalities other than those as-
sociated with loss of trigeminal nerve function.
Surgically associated morbidity should decrease as
surgical technique and experience with tumors in this
location increase. The disease was progressive in all
of the cases not treated, many of which died due to
infiltration of the tumor into adjacent vital brain stem
and forebrain structures. In this instance, aggressive
local treatment, with surgery or possibly radiation
therapy, may be necessary to arrest the progression of
this tumor.
a
Conray; Mallinckrodt Medical, St. Louis, MO
b
Magnevist; Berlex Laboratories, Cedar Knolls, NJ
c
Gelfoam; The Upjohn Co., Kalamazoo, MI
Acknowledgments
The authors would like to thank Alexander de
Lahunta, DVM, PhD of the Department of Clinical
Sciences, College of Veterinary Medicine, Cornell
University for his interpretation of the surgical bi-
opsy from one of the dogs of this report and Dr. Andy
Platts of the Department of Radiology, Royal Free
Hospital, London, United Kingdom for assistance in
interpreting some of the magnetic resonance images.
References
1. Hughes RAC. Diseases of the fifth cranial nerve. In: Dyck PJ, Thomas
PK, eds. Peripheral neuropathy. 3rd ed. Philadelphia: WB Saunders,
1993:801–17.
2. Summers BA, Cummings JF, de Lahunta A. Neoplasia and the peripheral
nervous system. In: Summers BA, Cummings JF, de Lahunta A, eds.
Veterinary neuropathology. St. Louis: Mosby, 1995:472–501.
3. Holliday TA, Higgins RJ, Turrel JM. Tumors of the nervous system. In:
Theilen GH, Madewell BR, eds. Veterinary cancer medicine. 2nd ed.
Philadelphia: Lea & Febiger, 1987:601–17.
4. LeCouteur RA. Tumors of the nervous system. In: Withrow SJ, MacEwen
EG, eds. Clinical veterinary oncology. Philadelphia: JB Lippincott,
1989:325–50.
5. Zachary JF, O’Brien DP, Ingles BW, et al. Multicentric nerve sheath
fibrosarcomas of multiple cranial nerve roots in two dogs. J Am Vet Med
Assoc 1986;188:723–6.
6. Zaki FA. Spontaneous central nervous system tumors in the dogs.
Vet Clin N Am 1977;7:153–63.
7. Cordy DR. Tumors of the nervous system and eye. In: Moulton JE, ed.
Tumors of domestic animals. 3rd ed. Berkeley: Univ Calif Press,
1990:640–65.
8. Braund KG. Neoplasia of the nervous system. Comp Cont Ed 1984;
6:717–22.
9. Beezley DN. A trigeminal ganglioneuroma in a dog. Cornell Vet
1969;59:585–93.
10. Vandevelde M, Braund KG, Hoff EJ. Central neurofibromas in two dogs.
Vet Path 1977;14:470–8.
11. St. Clair LE, Dafanie AH. Intracranial nerve root tumors—report of a
neoplasm (neurofibroma) of the trigeminal nerve in a dog. J Am Vet Med
Assoc 1957;131:188–91.
January/February 1998, Vol. 34
12. Carpenter JL, King NW Jr, Abrams KL. Bilateral trigeminal nerve
paralysis and Horner’s syndrome associated with myelomonocytic neo-
plasia in a dog. J Am Vet Med Assoc 1987;191:1594–6.
13. Christopher MM, Metz AL, Klausner J, et al. Acute myelomonocytic
leukemia with neurologic manifestations in the dog. Vet Path
1986;23:140–7.
14. Simpson ST, Kloop L, Hathcock JT. What is your neurologic diagnosis?
J Am Vet Med Assoc 1995;206:621–2.
15. El-Kalliny M, van Loveren H, Keller JT, Tew JM Jr. Tumors of the
lateral wall of the cavernous sinus. J Neurosurg 1992;77:508–14.
16. Lye RH, Ramsden RT, Stack JP, Gillespie JE. Trigeminal nerve tumor:
comparison of CT and MRI. J Neurosurg 1987;67:124–7.
17. Samii M, Migliori MM, Tatagiba M, Babu R. Surgical treatment of
trigeminal schwannomas. J Neurosurg 1995;82:711–8.
18. Pollack IF, Sekhar LN, Jannetta PJ, Janecka IP. Neurilemomas of the
trigeminal nerve. J Neurosurg 1989;70:737–45.
19. Bullitt E, Tew JM, Boyd J. Intracranial tumors in patients with facial
pain. J Neurosurg 1986;64:865–71.
Trigeminal Nerve Sheath Tumor 25
20. Levinthal R, Bentson JR. Detection of small trigeminal neurinomas.
J Neurosurg 1976;45:568–75.
21. Yasui T, Hakuba A, Kin SH, Nishimura S. Trigeminal neurinomas:
operative approach in eight cases. J Neurosurg 1989;71:506–11.
22. McCormick PC, Bello JA, Post KD. Trigeminal schwannoma.
J Neurosurg 1988;69:850–60.
23. King TT. Clinical presentation and treatment of tumors of the cranial
nerves and spinal roots. In: Dyck PJ, Thomas PK, eds. Peripheral
neuropathy. 3rd ed. Philadelphia: WB Saunders, 1993:1599–622.
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 Extraskeletal Osteosarcomas in Dogs:
14 Cases
Fourteen dogs (11 females, three males) with extraskeletal osteosarcomas
(EsOSAs) were identified. The median age was 11.5 years. The median body weight
was 18 kg. The primary sites of the EsOSAs were the spleen (n=6), mammary gland
(n=3), lung (n=2), and one each in the skin, axilla, and mesenteric root. The overall
median survival time was 74 days. The only factor which was found to be prognostic
for survival was the use of chemotherapy (p of 0.02). Cases which did not have
chemotherapy were 3.62 times as likely to die a tumor-related death than cases
which had chemotherapy. J Am Anim Hosp Assoc 1998;34:26–30.

Charles A. Kuntz, DVM, MS Introduction

William S. Dernell, DVM, MS
Barbara E. Powers, DVM, PhD
Stephen Withrow, DVM
RS
Extraskeletal osteosarcomas (EsOSAs) are uncommon tumors in
dogs.1–13 Approximately 34 cases have been reported previously in
the veterinary literature. Diagnosis depends on the satisfaction of the
following criteria: 1) uniform morphological pattern of sarcomatous
tissue that excludes the possibility of mixed mesenchymal tumor; 2)
production of malignant osteoid or bone; 3) high mitotic index; and 4)
exclusion of osseous origin. 3,14 Previously reported cases have in-
volved the liver,4,11 esophagus, 12 upper respiratory tract, 6 jejunum, 9,14
lung,7 retroperitoneum,10 anal sac,15 spleen, 14 mammary gland, 13 ad-
renal gland, eye, testicle, vagina, kidney, and mesentery. 3 Extra-
skeletal osteosarcomas are malignant tumors with distant metastases
occurring in 64% of cases.3 Survival times with surgery have ranged
from one to 175 days, with one case surviving 43 months.1
Although histopathological descriptions of EsOSAs exist, the clini-
cal course has not been described completely. The majority of cases
reported in the veterinary literature are individual patients, many of
which were euthanized at initial diagnosis.1,2,4,7–12,14,16 The purpose of
this study was to describe the clinical features of EsOSA in dogs,
with reference to the effect of treatment.

Materials and Methods

From the Comparative Oncology Unit
(Kuntz, Dernell, Withrow) and the
Department of Pathology (Powers),
College of Veterinary Medicine and
Biomedical Sciences,
Colorado State University,
Fort Collins, Colorado 80523.
Dogs which presented to the Colorado State University Veterinary
Teaching Hospital (CSU-VTH) with EsOSAs (according to the previ-
ously mentioned criteria) were included in this study. All histopatho-
logical samples were evaluated by a single pathologist (Powers).
Tumors were classified and graded according to a previously de-
scribed scale used to interpret histopathological samples from hu-
mans with EsOSAs.17 An attempt to diagnose an osseous primary
lesion was made in all cases by nuclear scintigraphy (n=1), necropsy
(n=4), and physical examination (n=14) [see Table]. Each case had
three-view thoracic radiographs at the time of diagnosis. Medical
records were examined for the following parameters: age at presenta-
tion, sex, weight, location of primary tumor, radiographic findings,
surgical and chemotherapeutic treatments implemented, date and lo-
cation of metastasis, date of local recurrence, and date and cause of
death. One case was lost to follow-up at 223 days after surgery. All
other cases were followed to death.

26 JOURNAL of the American Animal Hospital Association

 Table
Dogs with Extraskeletal Osteosarcomas

Survival Method Used to Chemo- Degree of Primary Final Cause

Age Weight Time Rule Out Primary Primary therapeutic Metastasis Differen- Pathological Out- of
Breed (yrs) Sex* (kg) (days) Osseous Lesion Location Surgery Agent Used Location tiation Process come Death
Keeshond 7 FS 14 223 Physical Mammary Mastectomy Doxorubicin — Well Osteoblastic LTF† —
January/February 1998, Vol. 34

examination gland
Shih tzu 10 FS 5 185 Physical Mammary Mastectomy Doxorubicin Lung Well Osteoblastic Dead Tumor;
examination gland euthanasia
Labrador 7 FS 29 8 Physical Skin None — — Poor Osteoblastic Dead Tumor;
retriever examination euthanasia
Mixed- 13 FS 24 146 Physical Spleen Splenectomy Doxorubicin Liver Poor Osteoblastic Dead Tumor;
breed dog examination euthanasia
Labrador 8 FS 27 64 Nuclear Lung Thoracotomy — Liver, lung, Poor Osteoblastic Dead Tumor;
retriever scintigraphy mediastinum death
Mixed- 13 FS 19 129 Physical Spleen Splenectomy — Liver, Poor Fibroblastic Dead Tumor;
breed dog examination omentum death
Toy poodle 12 FS 7 130 Physical Axilla Amputation Cisplatin Lung Poor Osteoblastic Dead Tumor;
examination death
Mixed- 8 FS 5 33 Necropsy Mammary None — Lung, heart Poor Osteoblastic Dead Tumor;
breed dog gland euthanasia
Shetland 12 FS 17 3 Necropsy Lung None — Lung Poor Osteoblastic Dead Tumor;
sheepdog euthanasia
Chesapeake 8 FS 44 1 Necropsy Mesenteric Abdominal — Liver Poor Osteoblastic Dead Tumor;
Bay root exploration euthanasia
retriever
Mixed- 17 MC 9 6 Physical Spleen Abdominal — Liver Poor Osteoblastic Dead Tumor;
breed dog examination exploration euthanasia
Golden 14 M 31 0 Necropsy Spleen Abdominal — Liver Poor Fibroblastic Dead Tumor;
retriever exploration euthanasia
Miniature 14 FS 5 16 Physical Spleen Splenectomy — — Poor Fibroblastic Dead Tumor;
schnauzer examination euthanasia
Golden 11 MC 39 74 Physical Spleen Splenectomy Cisplatin Liver Poor Osteoblastic Dead Tumor;
retriever examination euthanasia

* FS=spayed female; MC=castrated male; M=male

Extraskeletal Osteosarcomas

†
LTF=lost to follow-up
27
28 JOURNAL of the American Animal Hospital Association
Figure 1—Kaplan-Meier survival curve for five dogs treated with
chemotherapy and six dogs not treated with chemotherapy.
Only cases not euthanized at diagnosis of EsOSA
were included in the survival analysis. Local recur-
rence free interval (LRFI) was defined as the time
between surgery at the CSU-VTH and clinical or ra-
diographic evidence of local recurrence. Metastasis
free interval (MFI) was defined as the time between
surgery and evidence of metastasis. Survival time
was defined as the time between surgery and death.
Cause of death was classified as tumor or nontumor
related. Survival times were determined by use of the
Kaplan-Meier product limit method.
Identification of variables prognostic for local re-
currence, metastasis, and survival was by univariate
log rank analysis. Variables evaluated included site
(i.e., mammary gland and lungs versus other), sex,
age at diagnosis (greater than or less than 10 years),
tumor diameter, surgical resection of tumor, presence
or absence of tumor calcification, administration of
chemotherapy following surgery, degree of histologi-
cal differentiation, and primary histological process
(i.e., fibroblastic, chondroblastic, or osteoblastic).
Only factors found to be prognostic in univariate
analysis were carried over to multivariate analysis
using Cox’s proportional hazards model.a Cases were
censored in LRFI, MFI, and survival analysis if local
recurrence, metastasis, or tumor-related death did not
occur, respectively. Statistical significance was es-
tablished at p less than 0.05.
Results
Fourteen cases (11 females, three males) were identi-
fied with EsOSAs [see Table]. No breeds appeared to
be overrepresented. Patient age ranged from seven to
17 years (median, 11.5 years). Body weight ranged
from five to 44 kg (median, 18 kg). The sites of the
presumed primary EsOSAs were the spleen (n=6),
mammary gland (n=3), lung (n=2), and one each in
January/February 1998, Vol. 34
the skin, axilla, and mesenteric root. Two cases (14%)
had well-differentiated tumors, and 12 (86%) had
poorly differentiated tumors. Three cases (21%) had
fibroblastic tumors, and 11 cases (79%) had osteo-
blastic tumors. Four (31%) of 13 cases which had
radiographs of the primary tumor available for evalu-
ation had calcification evident within the tumor.
Metastasis was present at diagnosis in eight (57%)
of 14 cases and at time of death in 11 (85%) of 13
cases which have died. One case which was lost to
follow-up had no evidence of metastasis at the time
(223 days) it was lost to follow-up. Metastases were
present in the lungs (n=5), the liver (n=7), the medi-
astinum (n=1), the omentum (n=1), and the heart
(n=1). No variables were found to be prognostic for
the development of metastasis. Two cases had local
recurrences following resection 14 days and 57 days
after surgery, respectively. No variables were found
to be prognostic for the development of local recurrence.
Regarding treatment, eight cases each had surgical
resection of the primary tumor. Three cases had ex-
ploratory surgery followed by euthanasia, and three
had no surgery performed (median survival time, eight
days). Five cases had chemotherapy following surgi-
cal resection of the primary tumor. Two cases each
had two doses of cisplatin at three-week intervals,
and three cases had five doses of doxorubicin at three-
week intervals. All cases which had chemotherapy
had surgical resection of their primary tumors. Three
of five cases receiving chemotherapy had evidence of
metastatic disease at the time of surgery. Of cases not
euthanized at diagnosis, the median survival time for
six cases not receiving chemotherapy was 33 days,
while the median survival time for five cases receiv-
ing chemotherapy was 146 days [Figure 1].
One case with a well-differentiated, mammary
EsOSA was lost to follow-up 223 days following
surgical treatment, with no evidence of disease. The
remaining 13 cases have died (n=3) or have been
euthanized (n=10) because of progression of their
tumors. The overall median survival time was 74 days.
The only factor which was found to affect survival
time significantly was the use of chemotherapy (p of
0.02). Cases which did not have chemotherapy were
3.62 times as likely to die a tumor-related death as
cases which had chemotherapy (95% confidence in-
terval [CI], 1.22 to 10.72).
Discussion
The diagnosis of EsOSA by definition requires the
elimination of an osseous primary bone lesion.1,14 In
five of 14 cases, this was confirmed by nuclear scin-
tigraphy or by necropsy. In the other nine cases, an
exhaustive search for an osseous primary tumor was
performed by physical examination and radiography.
Diagnosis of a primary EsOSA should raise suspicion
January/February 1998, Vol. 34
in the clinician of the possibility of an osseous pri-
mary lesion. Although these diagnostic measures can-
not rule out the presence of small, primary bone
lesions, none were identified by owner follow-up or
physical examination. Ideally, nuclear scintigraphy,
whole body radiography, necropsy, or a combination
of these diagnostics should be performed in search of
an osseous primary bone lesion in all cases of sus-
pected EsOSA.
The demographic data for dogs with EsOSA is
different from that for dogs with skeletal osteosar-
coma (SOSA). Skeletal osteosarcoma typically is as-
sociated with large-breed dogs, with only 5% of SOSA
occurring in dogs weighing less than 15 kg.18 In this
study of EsOSA, 43% of dogs weighed less than 15
kg. Skeletal osteosarcoma typically metastasizes to
the lung and bone, 19 while in this study, 86% of dogs
had tumors in places not associated typically with
SOSA metastasis. The median age in this study was
11.5 years, while with SOSA, the median age is seven
years. The median age of 11.5 years nearly is identi-
cal to that of the largest collection of EsOSAs in the
veterinary literature, all of which were confirmed by
complete necropsies. 3 The median body weight, sex
distribution, and survival time in this study also are
nearly identical with those reported in the aforemen-
tioned study. In addition, if these represented meta-
static lesions, then chemotherapy should not have had
any effect on survival time, as no effect of a single-
agent chemotherapy has been shown in dogs with
SOSA and measurable metastatic disease. 20 Given
these factors, it becomes apparent that this study rep-
resents a segment of population which is distinct from
that typical with SOSA and similar to that previously
reported for EsOSA.
It has been suggested that EsOSAs of the mam-
mary glands and lungs not be included with other
cases of EsOSA because of their bimodal (i.e., mes-
enchymal and epithelioid), histological content and
assumed origin from stromal metaplasia of associated
adenocarcinomas. 3 They were included in this study,
and based on analysis of survival and metastasis they
do not appear to behave differently from EsOSAs of
other sites. None of the samples in this study had
histopathlogical evidence of epithelioid origin. The
two well-differentiated tumors were of mammary ori-
gin and therefore may represent more benign tumor
behavior; the dogs had the longest survival times
(185 and 223 days) in the entire study. Both cases
were treated with chemotherapy. Determination of
the effect of variation in tumor differentiation was
not possible, because there were only two tumors
which were well differentiated.
The lack of tumor calcification in most of the cases
in this study is in contrast with what has been re-
ported previously in the literature regarding
Extraskeletal Osteosarcomas 29
EsOSAs. 1,2,5,8,9,11,14 This finding is important because
it demonstrates that an EsOSA cannot be ruled out
based on the lack of radiographic evidence of tumor
calcification. Calcification of the tumor did not affect
recurrence, metastasis, or survival.
Treatment of EsOSAs has not been evaluated in
the veterinary literature. Even with a relatively small
sample, the use of chemotherapy significantly affected
survival times in cases which were not euthanized at
diagnosis. This is consistent with what is recom-
mended in the human literature. 21 The effect of the
type and dosage regimen of chemotherapy adminis-
tered could not be determined because of the small
sample size and lack of statistical power.
Based on this and previous studies, dogs with
EsOSAs have a worse prognosis for survival and me-
tastasis than dogs with SOSAs. The median survival
time of cases not receiving chemotherapy which were
not euthanized after diagnosis was 33 days. This is
shorter than the median survival times of 139 22 to
21823 days in dogs with SOSAs not having chemo-
therapy. The median survival time in cases receiving
chemotherapy following surgical resection of EsOSA
was 146 days. This also is shorter than the median
survival times of 30124 to 415 23 days reported in dogs
receiving chemotherapy following surgical resection
of SOSA. In this study, 57% of cases had metastatic
disease at the time of diagnosis, in contrast to 10% of
dogs with SOSA. 19,22 The apparently poorer progno-
sis may be because EsOSA represents a more malig-
nant variant of osteosarcoma or because patients with
EsOSA present later in the disease course due to more
subtle clinical signs. Alternatively, some EsOSAs ac-
tually may represent metastasis from undetected pri-
mary lesions. Owners also may be less likely to pursue
aggressive therapy for dogs with EsOSA, which char-
acteristically are older than dogs with SOSA.
Extraskeletal osteosarcoma has a similar behav-
ior in human patients. 25–27 It is rare, in that it rep-
resents less than 1% of soft-tissue sarcomas. It is
more malignant than SOSA, with the five-year sur-
vival rate averaging 20%. 25 As in dogs, human
patients with EsOSA typically are older than those
with SOSA, and females are somewhat predis-
posed. A history of prior trauma is present in ap-
proximately 10% of human patients. In contrast to
EsOSA in dogs, extremities are affected most com-
monly in humans. Recurrence and metastasis rates
following surgery are approximately 44% and 65%,
respectively. 26,27 Patients with predominately chon-
droblastic tumors fare better than those with os-
teoblastic tumors. 27 Initial size is not related to
prognosis. The use of surgery followed by adju-
vant chemotherapy is the recommended course of
treatment. 25 Otherwise, the prognosis for patients
with EsOSA is dismal.
30 JOURNAL of the American Animal Hospital Association January/February 1998, Vol. 34

Conclusion
Extraskeletal osteosarcoma appears to have demo-
graphic characteristics that are distinct from SOSA.
The prognosis for EsOSA appears to be worse than
that for SOSA. Chemotherapy following surgical re-
moval of the primary tumor appears to offer the best
opportunity for survival,21 but even with the use of
chemotherapy, the prognosis is poor. Exhaustive ef-
forts must be made to find an osseous primary tumor
before the diagnosis of EsOSA can be confirmed.
23. Mauldin GN, Matus RE, Withrow SJ, Patnaik AK. Canine osteosarcoma:
treatment by amputation and adjuvant chemotherapy using doxorubricin
and cisplatin. J Vet Int Med 1988;2:177–80.
24. Shapiro W, Fossum TW, Kitchell BE, Couto CG, Theilen GH. Use of
cisplatin for treatment of appendicular osteosarcoma in dogs. J Am Vet
Med Assoc 1988;192:507–10.
25. Bane BL, Evans HL, Ro JY, et al. Extraskeletal osteosarcoma. A
clinicopathologic review of 26 cases. Cancer 1990;65:2762–70.
26. Chung EB, Enzinger FM. Extraskeletal osteosarcoma. Cancer
1987;60:1132–42.
27. Lee JS, Fetsch JF, Wasdhal DA, Lee BP, Pritchard DJ, Nascimento AG.
A review of 40 patients with extraskeletal osteosarcoma. Cancer
1995;76:2253–9.

a
Statistical package for the Social Sciences; Jandel Scientific Software, San
Rafael, CA

References
1. Kipnis RM, Conroy JD. Canine extraskeletal osteosarcoma. Can Pract
1992;17:34–7.
2. Alexander JW, Walker MA, Easley JR. Extraskeletal osteosarcoma in a
dog. J Am Anim Hosp Assoc 1979;15:99–102.
3. Patnaik AK. Canine extraskeletal osteosarcoma and chondrosarcoma: a
clinicopathologic study of 14 cases. Vet Path 1990;27:46–55.
4. Patnaik AK, Lui SK, Johnson GF. Extraskeletal osteosarcoma of the
liver in a dog. J Sm Anim Pract 1976;17:365–70.
5. Bartels JE. Canine extraskeletal osteosarcoma: a clinical communica-
tion. J Am Anim Hosp Assoc 1975;11:307–9.
6. Brodey RS, O’Brien J, Bergs P, Roszel JE. Osteosarcoma of the upper
airways in the dog. J Am Vet Med Assoc 1969;155:1460–4.
7. Seiler RJ. Primary pulmonary osteosarcoma in a dog with associated
hypertropic osteopathy. Vet Path 1979;16:369–71.
8. Norrdin RW, Lebel JC, Chitwood JS. Extraskeletal osteosarcoma in a
dog. J Am Vet Med Assoc 1971;158:729–34.
9. Eckerlin RH, Fowler EH. Chondroblastic osteosarcoma in the jejunum
of a dog. J Am Vet Med Assoc 1976;168:691–3.
10. Salm R, Mayes SEF. Retroperitoneal osteosarcoma in a dog. Vet Rec
1969;85:651–3.
11. Jeraj K, Yano B, Osborne CA. Primary hepatic osteosarcoma in a dog.
J Am Vet Med Assoc 1981;179:1000–3.
12. Turnwald GH, Smallwood JE, Helman RG. Esophageal osteosarcoma in
a dog. J Am Vet Med Assoc 1979;174:1009–11.
13. Misdorp W, Cotchin E, Hampe JF. Canine malignant mammary tumors.
Vet Path 1971;8:99–117.
14. Schena CJ, Stickle RL, Dunstan RW, et al. Extraskeletal osteosarcoma
in two dogs. J Am Vet Med Assoc 1989;194:1452–6.
15. Bardet JF, Weisbrode S, DeHoff WD. Extraskeletal osteosarcomas:
literature review and a case presentation. J Am Anim Hosp Assoc
1983;19:601–4.
16. Ewing GO. Primary mixed sarcoma in a Labrador. Calif Vet 1967;
21:18–9.
17. Sordillo PP, Hajdu SI, Magill GB, Golbey RB. Extraosseous osteogenic
sarcoma: a review of 48 patients. Cancer 1993;51:727–34.
18. Kistler KR. Canine osteosarcoma: 1,462 cases reviewed to uncover
patterns of height, weight, breed, sex, age and site of involvement. In:
Phi Zeta Awards. Philadelphia: School of Veterinary Medicine, Univer-
sity of Pennsylvania, 1981;17.
19. Brodey RS, Riser WH. Canine osteosarcoma: a clinicopathological
study of 194 cases. Clin Orthop Rel Res 1969;62:54–64.
20. Ogilvie GK, Straw RC, Jameson VJ, et al. Evaluation of single-agent
chemotherapy for treatment of clinically evident osteosarcoma me-
tastases in dogs: 45 cases (1987–1991). J Am Vet Med Assoc
1993;202:304–6.
21. Patel RS, Benjamin RS. Primary extraskeletal osteosarcoma—experi-
ence with chemotherapy. J Nat Cancer Inst 1995;87:1331–3.
22. Spodnick GJ, Berg J, Rand WM, et al. Prognosis for dogs with appen-
dicular osteosarcoma treated by amputation alone: 162 cases (1978–
1988). J Am Vet Med Assoc 1992;200:995–9.
 Fibrosarcoma in the Distal Radius and
Carpus of a Four-Year-Old Persian
A four-year-old Persian was presented for evaluation of a nonweight-bearing, left
forelimb lameness. Radioulnar and pancarpal osteolysis with minimal periosteal
reaction were seen on radiographs of the antebrachium. Cytological examinations
of fine-needle aspirates and impression smears were suggestive of sarcoma. After
forequarter amputation, histopathological examination provided a diagnosis of
fibrosarcoma with axillary lymph-node metastasis. J Am Anim Hosp Assoc 1998;34:31–3.

James L. Cook, DVM Introduction

James R. Turk, DVM, PhD,
Diplomate ACVP
James L. Tomlinson, DVM, MVSc,
Diplomate ACVS
Louis A. Corwin, DVM, PhD,
Diplomate ACVR
Deborah C. Shaw, DVM
C sity of Missouri-Columbia Veterinary Medical Teaching Hospital for
From the Departments of Small Animal
Surgery (Cook, Tomlinson),
Pathobiology (Turk), and
Radiology (Corwin),
Veterinary Teaching Hospital and
Diagnostic Laboratory,
University of Missouri-Columbia,
379 East Campus Drive,
Columbia, Missouri 65211 and the
Laurie Animal Hospital (Shaw),
P.O. Box 1061,
Laurie, Missouri 65038.
Fibrosarcomas account for approximately 5% to 12% of all feline
neoplasms. 1,2 The primary cause of fibrosarcomas in young (mean
age, three years) cats is feline sarcoma virus (FeSV). 1–4 The neo-
plasms associated with FeSV are usually multicentric, poorly differ-
entiated, and highly invasive. 1,2 Solitary fibrosarcomas tend to occur
in older (mean age, 10 years) cats and have no relationship to FeSV or
feline leukemia virus (FeLV).1–3 The solitary fibrosarcomas closely
resemble canine fibrosarcomas. 3
Case Report
A four-year-old, castrated male Persian was presented to the Univer-
evaluation of a nonweight-bearing, left forelimb lameness. The lame-
ness first was observed by the owner eight months prior to admission
after known trauma. The lameness had progressed from intermittent
episodes of weight-bearing lameness to complete nonweight-bearing.
The cat had been treated with multiple attempts at bandaging and
splinting the limb and several courses of antibiotics, with no im-
provement.
On presentation, the cat was alert and responsive but was cachectic
and had a poor hair coat. His rectal temperature was 39.2˚ C, heart
rate was 200 beats per minute, and respiratory rate was 50 breaths per
minute. A nonweight-bearing lameness of the left forelimb was ob-
served. The limb was swollen over the area of the distal radius and
carpus, and palpation of the area elicited signs of pain. No neurologi-
cal abnormalities were found.
Osteolysis of the distal radius, distal ulna, and the proximal row of
carpal bones was noted on radiographs of the left antebrachium [Fig-
ures 1A, 1B]. Punctate lytic lesions and a well-modeled periosteal
reaction were evident over the mid-to-distal radius. Resorptive and
remodeling changes of the distal row of carpal bones and the proxi-
mal fourth and fifth metacarpal bones also were present. Caudal
subluxation of the radiocarpal joint was noted. Radiographs of the
thorax were considered to be within normal limits. The differential
diagnoses of primary bone neoplasia, associated soft-tissue neopla-
sia, metastatic disease, and osteomyelitis were considered.
Complete blood count and biochemistry panel values were within
reference ranges. A test for FeLV antigen a was negative. Fine-needle

JOURNAL of the American Animal Hospital Association 31

32 JOURNAL of the American Animal Hospital Association
Figure 1A Figure 1B
Figures 1A, 1B—(A) Lateral and (B) craniocaudal radio-
graphic views of the left antebrachium demonstrating
pancarpal osteolysis.
Figure 2—Photomicrograph of a section of tumor demonstrating
bony invasion and osteonecrosis (Hematoxylin and eosin stain,
400X; bar=50 µ).
aspirates of the swollen area of the limb were ob-
tained using a 22-gauge needle and a 6-cc syringe.
Biopsies using a Jamshidi bone biopsy needleb also
were obtained. Fine-needle aspirate samples and im-
pression smears made from the biopsy samples were
examined cytologically. Nucleated cells (with low-
to-moderate cellularity), erythrocytes, and tissue de-
bris were noted. The nucleated cells consisted of small
and large spindle cells, osteoblasts, and osteoclasts.
Some of the spindle cells contained indistinct nucleoli
that were greater than 5 µ in diameter. Cytology of
January/February 1998, Vol. 34
Figure 3—Photomicrograph of a tissue section from the left
axillary lymph node demonstrating neoplastic cells consistent
with fibrosarcoma (Hematoxylin and eosin stain, 200X; bar=
100 µ).
the aspirates and impression smears was considered
to be consistent with sarcoma. Given the presumptive
diagnosis, associated prognosis, and options for treat-
ment, the owners opted for forequarter amputation as
the sole treatment.
A forequarter amputation was performed the fol-
lowing day, and the entire limb and axillary lymph
node were submitted for histopathological evaluation.
Immediately following extubation, the cat demon-
strated signs of dyspnea and tachypnea. Dexametha-
sone sodium phosphate (2 mg/kg body weight,
intravenously [IV]) and butorphanol (0.1 mg/kg body
weight, IV) were administered and resulted in resolu-
tion of the postoperative respiratory problems. The
cat recovered without further incident and was dis-
charged two days after surgery.
Sections of the distal radius and radiocarpal bone
with associated articular cartilage were examined his-
tologically. Hyaline cartilage and lamellar bone were
incarcerated by neoplastic, pleomorphic spindle cells
with prominent single or multiple nucleoli [Figure 2].
Neoplastic cells were present within marrow spaces.
Osteonecrosis of the affected bone also was evident.
Neoplastic spindle cells similar to those in the
antebrachium were arranged in irregular bundles and
whorls within the subcapsular sinuses of the axillary
lymph node [Figure 3]. Mitotic figures ranged from
zero to one per 400X field. Histopathology was con-
sistent with fibrosarcoma of the distal antebrachium
with bony invasion and lymph-node metastasis.
The cat was examined by another veterinarian two
weeks after surgery for suture removal, and at that
time the owner reported that the cat was doing well
with no complications related to the surgery. During
a telephone conversation with the owner two months
after surgery, the cat was reported to have no evi-
dence of recurrence, metastasis, or related complica-
tions. The cat had no health problems or evidence of
January/February 1998, Vol. 34
related disease on routine examination six months
after surgery. The owner reported that the cat died
suddenly of apparently unrelated causes seven months af-
ter surgery. A postmortem examination was not performed.
Discussion
Fibrosarcomas in cats can be divided into two distinct
categories based on their relationship to FeSV. The
virus that induces the neoplastic transformation of
cells is a recombinant hybrid of host genome and
FeLV.2–4 The causal virus can be found only in cats
that have at some point been infected with FeLV. 2–4
Fibrosarcomas associated with FeSV usually occur in
younger cats and tend to be multiple, poorly differ-
entiated, and highly invasive. 1–4 Treatment is not
recommended. 1,2
Fibrosarcomas that are not associated with FeSV
normally occur in older cats. These neoplasms re-
semble their canine counterpart in that they are soli-
tary, well-differentiated tumors. Fibrosarcomas are
fibroblastic neoplasms that produce bundles of col-
lagenous fibers without neoplastic bone, osteoid, or
cartilage.2,5–8 Fibrosarcomas of bone arise from med-
ullary or periosteal connective tissue. 5–7 Radiographi-
cally, osteolysis predominates with minimal reactive
response. 5–7 Histologically, the neoplasm consists of
spindle cells (i.e., fibroblasts) arranged in fascicles or
syncytia, with or without collagen. 5,6,8
Recent reports have indicated the possibility of
vaccination-induced fibrosarcomas developing in cats
at the site of administration of various vaccines.9–11
Further investigation is needed to determine the causal
relationship and the pathophysiology associated with
the development of these neoplasms. In the current
case report, vaccination-induced fibrosarcoma was
ruled out based on the vaccination history of the cat.
Well-differentiated fibrosarcomas usually do not
metastasize. 6,8 Less well-differentiated fibrosarcomas
may produce hematogenous metastases. 6,8 Some fi-
brosarcomas have been shown to follow lymphatic
chains.1,2 Approximately 10% have demonstrated de-
finitive metastases, most often pulmonary. 3,7 Local
recurrence is common. 1–3,6–8 Mitotic index affects the
rapidity, but not the prevalence, of recurrence.3 Radi-
cal surgical excision (i.e., amputation) is recom-
mended. 2,5,6,8 No evidence has been reported to
support the use of adjunctive chemotherapy. The prog-
nosis is guarded when there is evidence of metastasis.
Based on the seronegativity of this cat for FeLV
and the histopathological findings, the neoplasm re-
ported presently would be categorized as a solitary,
nonFeSV-induced fibrosarcoma. The radiographic,
gross, and histopathological findings are consistent
with periosteal origin. The unusual findings reported
in this case involve the relatively young age of the
cat, the radiographic findings of radioulnar and
Fibrosarcoma 33
pancarpal osteolysis, and the demonstration of me-
tastasis to the regional lymph node.
Conclusion
Fibrosarcoma is a significant disease entity in the
feline population. Knowledge of the possible etiolo-
gies, clinical findings, and biological behavior of
these neoplasms is essential to effective diagnosis
and management of affected cats. Feline leukemia
virus status and vaccination history are vital in deter-
mining the etiology of feline fibrosarcomas. Radical
surgical excision of fibrosarcomas should be per-
formed only in cases of solitary, nonFeSV-induced
neoplasms. Careful evaluation and continued moni-
toring for metastatic disease and local recurrence are
recommended.
This case report describes a solitary, nonFeSV-
induced fibrosarcoma of proposed periosteal origin
involving the forelimb of a cat. The diagnostic find-
ings of interest included radioulnar and pancarpal
involvement and regional lymph-node metastasis. Fi-
brosarcoma should be a diagnostic differential in cats
of all ages with radiographic signs of osteolysis in the
extremities, even with transarticular involvement.
a
Feline Leukemia Virus Antigen Test Kit; IDEXX Laboratories,
Westbrook, ME
b
Baxter Healthcare Corp.; Valencia, CA
References
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MacEwen EG, eds. Clinical veterinary oncology. Philadelphia: JB
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8. LaRue SM, Withrow SJ. Tumors of the skeletal system. In: Withrow SJ,
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9. Hendrick MJ, Shofer FS, Goldschmidt MH, et al. Comparison of fibro-
sarcomas at vaccination sites and at nonvaccination sites in cats: 239
cases (1991–1992). J Am Vet Med Assoc 1994;205:1425–9.
10. Kass PH, Barnes WG, Spangler WL, et al. Epidemiologic evidence for
a causal relationship between vaccination and fibrosarcoma tumorigen-
esis in cats. J Am Vet Med Assoc 1993;203:396–405.
11. Hendrick MJ, Goldschmidt MH, Shofer FS, et al. Postvaccinal sarcomas
in the cat: epidemiology and electron probe microanalytical identifica-
tion of aluminum. Cancer Res 1992;52:5391–4.
Editorial Review Board
Joseph W. Alexander
Stillwater, Oklahoma
Mark A. Anderson
Florissant, Missouri
Claudia J. Baldwin
Ames, Iowa
Jan E. Bartels
Auburn, Alabama
Joseph W. Bartges
Athens, Georgia
Bonnie V. Beaver
College Station, Texas
G. John Benson
Urbana, Illinois
James P. Boulay
Boston, Massachusetts
Nancy O. Brown
Plymouth Meeting, Pennsylvania
Karen L. Campbell
Urbana, Illinois
Phyllis A. Ciekot
Scottsdale, Arizona
James R. Cook, Jr.
Cooper City, Florida
Thomas M. Craig
College Station, Texas
Charlotte Davies
Blacksburg, Virginia
William S. Dernell
Fort Collins, Colorado
Jennifer Devey
Springfield, Virginia
Curtis Dewey
College Station, Texas
W. Jean Dodds
Santa Monica, California
R. Tass Dueland
Madison, Wisconsin
Nicole Ehrhart
Urbana, Illinois
Theresa W. Fossum
College Station, Texas
Paul C. Gambardella
Boston, Massachusetts
Urs Giger
Philadelphia, Pennsylvania
Rebecca E. Gompf
Knoxville, Tennessee
Robert A. Green
College Station, Texas
Gary M. Greene
Covington, Louisiana
Cathy L. Greenfield
Urbana, Illinois
Craig Griffin
San Diego, California
Thelma Lee Gross Royce Roberts
W. Sacramento, California Athens, Georgia
Sandee M. Hartsfield Kenita S. Rogers
College Station, Texas College Station, Texas
Cheryl S. Hedlund Robert C. Rosenthal
Baton Rouge, Louisiana Rochester, New York
Charles M. Hendrix Gerard J. Rubin
Auburn, Alabama Dallas, Texas
Ann L. Johnson Michael Schaer
Urbana, Illinois Gainesville, Florida
Spencer A. Johnston Scott Schelling
Blacksburg, Virginia Boston, Massachusetts
Thomas J. Kern Robert E. Schmidt
Ithaca, New York W. Sacramento, California
Kerry L. Ketring Linda Shell
Cincinnati, Ohio Blacksburg, Virginia
George E. Lees Peter K. Shires
College Station, Texas Blacksburg, Virginia
Patricia J. Luttgen Charles E. Short
Lakewood, Colorado Ithaca, New York
Mary Mahaffey Mitchell D. Song
Athens, Georgia Scottsdale, Arizona
Charles L. Martin Rebecca L. Stepien
Athens, Georgia Madison, Wisconsin
Robert A. Martin Jean Stiles
Blacksburg, Virginia Athens, Georgia
Robert E. Matus Priscilla K. Stockner
Oneonta, New York San Marcos, California
Neal Mauldin Cheryl Swenson
New York, New York East Lansing, Michigan
Charles J. McGrath Joseph Taboada
Blacksburg, Virginia Baton Rouge, Louisiana
D. J. Meyer Jennifer S. Thomas
W. Sacramento, California College Station, Texas
Matthew W. Miller John C. Thurmon
College Station, Texas Urbana, Illinois
Eric Monnet David M. Tinsley
Fort Collins, Colorado Gloucester, Ontario
Thomas W. Mulligan William J. Tranquilli
El Cajon, California Urbana, Illinois
Mark J. Novotny Grant H. Turnwald
Groton, Connecticut Stillwater, Oklahoma
Frederick W. Oehme Don R. Waldron
Manhattan, Kansas Blacksburg, Virginia
Carl A. Osborne Wendy A. Ware
St. Paul, Minnesota Ames, Iowa
Mark G. Papich Stephen D. White
Raleigh, North Carolina Fort Collins, Colorado
Rhonda D. Pinckney Michael D. Willard
Madison, Wisconsin College Station, Texas
Barbara E. Powers Alice M. Wolf
Fort Collins, Colorado College Station, Texas
Jean D. Powers J. Paul Woods
Columbus, Ohio Stillwater, Oklahoma
Bernhard Pukay
Ottawa, Ontario
34
 Isolated Right-Ventricular Hypertrophy
Associated with Severe Pulmonary
Vascular Apolipoprotein A1-Derived
Amyloidosis in a Dog
A 12-year-old dachshund was referred for respiratory distress, coughing, and weight
loss. Cyanosis, dyspnea, tachypnea, and harsh lung sounds were noted on physical
examination. Polycythemia with an increased number of nucleated red blood cells;
right atrial enlargement; severe interstitial-to-alveolar pattern in all lung fields; and
peripheral, echogenic, pulmonary masses were observed. Cytological examination
of pulmonary aspirates indicated possible pulmonary carcinoma. The dog was
euthanized at the owner’s request. Isolated right-ventricular hypertrophy and
pulmonary arteriopathy with amyloid deposits of apolipoprotein A1 were identified
upon necropsy and histopathology. Pulmonary vascular amyloidosis should be
considered in the differential diagnoses of respiratory distress in aged dogs.
J Am Anim Hosp Assoc 1998;34:35–7.

Karen K. Faunt, DVM Case Report

Jim R. Turk, DVM, PhD
Leah A. Cohn, DVM, PhD
John R. Dodam, DVM, PhD
Kenneth H. Johnson, DVM, PhD
C other significant abnormalities were noted. A severe and diffuse in-
From the Departments of Veterinary
Medicine and Surgery (Faunt, Cohn,
Dodam) and
Veterinary Pathobiology (Turk),
Veterinary Medical Teaching Hospital,
Clydesdale Hall,
University of Missouri,
379 East Campus Drive,
Columbia, Missouri 65211 and the
Department of Veterinary Pathobiology
(Johnson),
College of Veterinary Medicine,
University of Minnesota,
1971 Commonwealth Avenue,
St. Paul, Minnesota 55108.
An 8.4-kg, 12-year-old, intact male dachshund presented to the Uni-
versity of Missouri Veterinary Medical Teaching Hospital on an
emergency basis for evaluation of progressive respiratory distress,
coughing, and weight loss of several weeks’ duration. Abnormalities
identified upon physical examination included cyanosis, dyspnea,
tachypnea (respiratory rate, 180 breaths per min), an increased capil-
lary refill time (three to four sec), and harsh lung sounds bilaterally
which obscured cardiac sounds. Body temperature was normal, and
femoral pulses were regular and strong at 126 beats per minute. No
terstitial-to-alveolar pattern in all lung fields was present on thoracic
radiographs [Figure 1].
Initial treatment consisted of placement in an enriched oxygen
(O 2) environment (40% O2 ) where the dog appeared less cyanotic and
less dyspneic. Two doses of furosemide (3 mg/kg body weight, intra-
venously [IV] q 2 hrs) for treatment of suspected pulmonary edema
were given, but no further improvement was seen.
Subsequent diagnostic evaluations included an electrocardiogram
(EKG), echocardiogram, complete blood count (CBC), serum chem-
istry panel, occult heartworm enzyme-linked immunoassay (ELISA),
and cytological evaluation of transthoracic, ultrasonographic-guided,
fine-needle lung aspirates. Increased amplitude of the P waves at 0.5
to 0.6 millivolts on the EKG indicated right atrial enlargement [Fig-
ure 2]. However, the cardiac ultrasonographic examination docu-
mented normal left-ventricular function and could not confirm right
atrial enlargement. Abnormalities on the CBC were polycythemia
(packed cell volume [PCV], 65%) with no evidence of dehydration
(normal albumin on the serum chemistry panel), and five nucleated
red blood cells (NRBCs) per 100 white blood cells (WBCs). No
significant abnormalities were identified on the serum chemistry
panel. The heartworm ELISA was negative. Irregular echogenic

JOURNAL of the American Animal Hospital Association 35

36 JOURNAL of the American Animal Hospital Association
Figure 1—Right lateral radiograph of a 12-year-old dachshund.
Note the severe and diffuse interstitial-to-alveolar pattern in all
lung fields.
Figure 2—Lead II electrocardiogram (EKG) from a 12-year-old
dachshund. Note the marked increase in amplitude of P waves
at 0.5 to 0.6 millivolts (indicated by arrow).
masses were observed along the visceral surface of
the lung fields during ultrasonographic examination.
Ultrasonographic-guided, transthoracic fine-needle
aspirates of the lung produced cells which were com-
patible with carcinoma cells microscopically. At this
time, the dog was euthanized at the owner’s request
due to a probable diagnosis of carcinoma, worsening
clinical signs, and a poor prognosis. A cosmetic
necropsy was obtained.
Significant necropsy and histopathological find-
ings included isolated right-ventricular hypertrophy,
pulmonary arteriopathy, and pulmonary arterial amy-
loid deposits of apolipoprotein A1. Isolated right-
ventricular hypertrophy was identified by cardiac
dissection at the time of necropsy based on a ratio of
the weight of the left ventricle (LV) plus interven-
tricular septum (S) to the weight of the right ventricle
(RV). The (LV+S)/RV equaled 1.91 (reference range,
2.76 to 3.88). 1 No other grossly apparent lesions in
the thoracic and abdominal viscera were found. Rou-
tine tissue samples were fixed in phosphate-buffered
10% formalin and processed for histopathology. Mul-
tifocal interstitial fibrosis and alveolar epithelial hy-
perplasia were identified on pulmonary tissue
sections. Additionally, accumulations of alveolar
macrophages adjacent to small, muscular pulmonary
arteries that contained multifocal accumulations of
January/February 1998, Vol. 34
Figure 3—Photomicrograph of a small, muscular, pulmonary
artery containing amyloid within the intima and media (Verhoeff’s
elastic stain, 400X; bar=24 µ).
Figure 4—Photomicrograph of a small, muscular, pulmonary
artery containing birefringent amyloid within the intima and
media (Congo Red stain, 400X; bar=24 µ).
faintly eosinophilic, fibrillar-to-amorphous material
were seen on hematoxylin and eosin (H&E)-stained
sections. In Congo red-stained sections, the material
within the pulmonary arteries was identified as amy-
loid on the basis of Congophilia and its pale green
birefringence upon polarization. In Verhoeff’s elas-
tic-stained sections, the amyloid was shown to reduce
the luminal diameter and to be contained within the
intima and media of pulmonary arteries with an exter-
nal diameter of 200 µ or less [Figures 3, 4]. Amyloid
was not present in the coronary arteries, liver, spleen,
pancreas, or kidney. The pulmonary amyloid was
positive for apolipoprotein A1 on immunohistochemi-
cal staining. 3
Pulmonary vascular amyloidosis is a newly reported
and apparently common condition in the aged dog,
seen in 22% of dogs over 10 years of age.2–4 Amyloid
is an aggregate of rigid, insoluble protein fibers in a
β-pleated sheet configuration that accumulates extra-
cellularly. In the dog, several known types of precur-
sor proteins are associated with amyloidosis. The
January/February 1998, Vol. 34 Pulmonary Vascular Amyloidosis 37

precursor protein found in canine pulmonary vascular hypoxemia. The large deposits of amyloid in small
amyloidosis is a lipoprotein normally found in circu- muscular arteries of the pulmonary vasculature could
lation, apolipoprotein A1. The current literature de- interfere with the normal redistribution of blood flow
scribes pulmonary amyloidosis as a benign condition to various pulmonary capillary beds in response to
associated with aging. 2–4 In this condition, deposits normal changes in alveolar ventilation. This would
of amyloid appear in the small, muscular pulmonary induce significant ventilation-perfusion mismatch and
arteries and are not seen in any other organ systems. arterial hypoxemia. Arterial hypoxemia stimulates in-
Previous reports found no association between these creased levels of erythropoietin, leading to exagger-
amyloid deposits and clinical disease. 2–4 The case ated erythropoiesis, polycythemia, and the presence
described herein demonstrates a possible clinical cor- of NRBCs.
relation between isolated right-ventricular hypertro- Pulmonary vascular amyloidosis in the dog may
phy and pulmonary vascular amyloidosis. not be limited to nonclinical, senile pathological
The more general condition of pulmonary amyloi- changes in the lung. Pulmonary vascular amyloidosis
dosis in humans is not an uncommon diagnosis; pul- should be considered as a cause of isolated right-
monary involvement is usually only one component ventricular hypertrophy. Indeed, this report suggests
of systemic amyloidosis and often is found concur- that right-ventricular hypertrophy, hypoxemia, and
rently with cardiac amyloidosis. 5 Localized pulmo- respiratory distress may be induced by severe pulmo-
nary amyloidosis refers to amyloid deposits that are nary vascular amyloidosis.
restricted to the respiratory tract and are categorized
as tracheobronchial, solitary or multiple nodular, or
diffuse pulmonary amyloidosis.5,6 In the diffuse pa- References
1. Turk JR, Turk MA, Root CR. Necropsy of the canine heart: a simple
renchymal form, amyloid is found in muscular arteri- technique for quantifying ventricular hypertrophy and valvular alter-
oles and alveolar septa, with a minority of cases ations. Comp Cont Ed Pract Vet 1983;5:905–10.
presenting only with primarily vascular deposits.6 2. Roertgen KE, Lund EM, O’Brien TD, Westermark P, Hayden DW,
Johnson KH. Apolipoprotein A1-derived pulmonary vascular amyloid in
In humans, pulmonary arterial hypertension and aged dogs. Am J Path 1995;147:1311–7.
clinical symptomatology can be caused by pulmonary 3. Johnson KH, Sletten K, Hayden DW, O’Brien TD, Roertgen KE,
amyloidosis. 6 Significant pulmonary arterial amyloid Westermark P. Pulmonary vascular amyloidosis in aged dogs. Am J Path
1992;141:1013–9.
deposits result in increased resistance to flow, de- 4. Schuh JCL. Pulmonary amyloidosis in a dog. Vet Path 1988;25:102–4.
struction of pulmonary capillary beds by amyloid in- 5. Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis—the Mayo
filtration of alveolar septa, and concurrent heart Clinic experience from 1980 to 1993. Ann Int Med 1996;124:407–13.
failure from cardiac amyloid deposits. 6 The prognosis 6. Shiue ST, McNally DP. Pulmonary hypertension from prominent vascu-
lar involvement in diffuse amyloidosis. Arch Int Med 1988;148:687–9.
for the patient when this occurs is very poor to grave.6
In the dog of this report, necropsy findings of
right-ventricular hypertrophy likely were secondary
to the arteriopathy resulting from pulmonary arterial
deposits of amyloid. The pulmonary interstitial fibro-
sis and alveolar epithelial hyperplasia seen on histo-
pathology were mild and unlikely to have caused
right-ventricular hypertrophy. No gross or histologi-
cal evidence of pulmonary airway disease, parenchy-
mal disease, or thoracic cage disease capable of
producing cor pulmonale was found, nor was evi-
dence of primary right-sided cardiac disease seen.
However, pulmonary thromboembolism cannot be
ruled out completely, even with necropsy.
It is unknown why the pulmonary aspirates re-
vealed cells consistent with carcinoma cells. Malig-
nant cells were not identified on multiple sections of
lung on histopathology. Perhaps without benefit of
preserved tissue architecture, hyperplastic alveolar
epithelial cells cytologically resembled neoplastic
cells.
While arterial O 2 saturation and partial arterial
pressure of oxygen (P aO 2) were not measured in this
case, central cyanosis, polycythemia, and the elevated
NRBC count were likely the result of chronic arterial
 The Use of Enalapril in the Treatment of
Feline Hypertrophic Cardiomyopathy
The clinical response to enalapril in 19 cats with hypertrophic cardiomyopathy (HCM)
was evaluated retrospectively. Eleven cats were in congestive heart failure (CHF) at
the time enalapril was prescribed, while only one cat was in CHF when the cats were
reexamined three-to-six months later. Significant changes in cardiac dimensions
were identified echocardiographically. No adverse effects on blood pressure, serum
creatinine, or potassium were noted. Although the preliminary data suggests that
enalapril is well tolerated and may contribute to some improvements in cats with
HCM, controlled, prospective studies are needed to prove the efficacy of enalapril in
this disease. J Am Anim Hosp Assoc 1998;34:38–41.

John E. Rush, DVM, MS Introduction

Lisa M. Freeman, DVM, PhD
Don J. Brown, DVM, PhD
Francis W. K. Smith, Jr, DVM
RS
From the Department of Medicine,
Tufts University School of
Veterinary Medicine,
200 Westboro Road,
North Grafton, Massachusetts 01536.
Hypertrophic cardiomyopathy (HCM), characterized by primary con-
centric hypertrophy, is a common disease in cats, estimated to occur
in approximately 1.6% of a hospital-based population.1 The goals of
long-term management of cats with HCM and congestive heart failure
(CHF) are 1) to prevent the development or recurrence of pulmonary
edema; 2) to improve diastolic ventricular filling; and 3) to prevent
thromboembolism. 2 The ideal method to accomplish these goals, how-
ever, is controversial. Diltiazem or a β-adrenergic receptor antago-
nist, in conjunction with furosemide, is usually the first-line therapy
in cats with HCM and CHF.2–4 The diuretic effect of furosemide acts
to reduce preload. Diltiazem, a calcium-channel antagonist, improves
diastolic function by enhancing left-ventricular relaxation, decreas-
ing heart rate, and dilating coronary arteries. 4 It also may have ben-
eficial effects by reducing left-ventricular wall thickness. 4
Beta-adrenergic antagonists reduce heart rate, reduce wall stress, and
may reduce left-ventricular outflow tract gradients.3,5 If the use of
diltiazem or β antagonists does not control CHF or halt progressive
cardiac hypertrophy, few therapeutic alternatives remain. Enalapril,
an angiotensin-converting enzyme (ACE) inhibitor, has been used
extensively in humans and in dogs with CHF. The use of enalapril has
been reported only anecdotally in cats with HCM. Some clinicians
feel ACE inhibition is contraindicated in HCM, especially in cats
with left-ventricular outflow tract obstruction. Arteriolar vasodila-
tion caused by ACE inhibitors is hypothesized to worsen the dynamic
outflow obstruction to ejection of blood by the left ventricle. 6 In
addition to their vasodilatory effects, however, ACE inhibitors also
have important tissue effects which can alter cardiac remodeling and
may modify the progression of cardiac hypertrophy in various animal
and human models of cardiac disease. 7–9 The purpose of this retro-
spective study was to evaluate the clinical and echocardiographic
responses to enalapril in cats with HCM.
Materials and Methods
The records of all cats with HCM treated at Tufts University Foster
Hospital for Small Animals between January 1989 and April 1995
were reviewed. Cats that did not have initial and follow-up examina-

38 JOURNAL of the American Animal Hospital Association

January/February 1998, Vol. 34
Table 1—Mean values for left-atrial dimension, interventricular
septal thickness, left-ventricular free wall thickness, and left-
ventricular internal dimension from the time of initiation of
enalapril to follow-up evaluation three-to-six months later
(mean±standard error of the mean).
Key:
LA=left atrial dimension (normal, 1.21±0.18 cm) 18
IVSd=interventricular septal thickness in diastole (normal,
0.50±0.07 cm)
IVSs=interventricular septal thickness in systole (normal,
0.76±0.12 cm)
LVWd=left-ventricular free wall thickness in diastole (normal,
0.46±0.05 cm)
LVWs=left-ventricular free wall thickness in systole (normal,
0.78±0.10 cm)
LVIDd=left-ventricular internal dimension in diastole (normal,
1.51±0.21 cm)
LVIDs=left-ventricular internal dimension in systole (normal,
0.69±0.22 cm)
* p of 0.05 or less compared to initial examination
+ p of 0.01 or less compared to initial examination
tions within six months of each other were excluded.
Serum biochemistry data, systolic blood pressure mea-
surements, electrocardiographic findings, and
echocardiographic measurements were recorded from
medical records of cats with HCM treated with
enalapril (with or without other medications) for
three-to-six months. Echocardiographic measure-
ments were reviewed and recorded in each case for
both two-dimensional (2-D) and 2-D-guided M-mode
techniques. Measurements recorded included left-
atrial and left-ventricular internal dimension, inter-
ventricular septum and left-ventricular free wall
thickness, and the presence of narrowing of the left-
ventricular outflow tract. Narrowing of the left-ven-
tricular outflow tract was defined as the presence of
systolic anterior motion of the mitral valve, subjec-
tive assessment of localized hypertrophy of the inter-
ventricular septum into the outflow tract, or both on
2-D echocardiography.
Data on indirect (i.e., Doppler) measurements of
systolic blood pressure, serum creatinine, and serum
potassium (assessed by automated analyzer a) was ob-
tained from medical records of cats that underwent
these procedures. The presence of CHF (based on
clinical or radiographic evidence) also was recorded.
Baseline and follow-up measurements within the
group were compared using paired t-tests, while cat-
Enalapril 39
egorical variables were analyzed with the Pearson’s
chi-square test.
Results
Nineteen cats treated with enalapril for at least three
months that had baseline and follow-up echocar-
diography performed within a six-month period were
identified. Seventeen of these cats were receiving
other cardiac medications (i.e., aspirin [n=15],
diltiazem [n=14], furosemide [n=11], and propranolol
[n=1]) at the time enalapril was initiated. Enalapril
was prescribed between two days and 64 months after
the initial diagnosis of HCM. The reasons for initiat-
ing enalapril included persistent CHF despite a con-
servative dosage of furosemide (n=8); progressive
left-atrial enlargement, left-ventricular hypertrophy,
or both (n=8); and lack of owner compliance with
other medications which required three doses per day
(n=3). Eight of the 19 cats received enalapril at a
dosage of 1.25 mg/cat per os (PO) every 24 hours,
and 11 cats received enalapril at a dosage of 2.50 mg/cat
PO every 24 hours (range, 0.19 to 0.69 mg/kg body
weight q 24 hrs).
Fifteen cats had CHF at some point in their disease
process. At the time of starting enalapril, 11 cats had
CHF, nine of which were diagnosed on the basis of
thoracic radiography. In the remaining two cats, CHF
was diagnosed on the basis of increased lung sounds
and jugular vein distention (n=1) or exercise intoler-
ance and tachypnea (n=1). In the latter two cases,
progressive left-atrial enlargement was evident
echocardiographically. When the cats were reexam-
ined three-to-six months later, only one cat was diag-
nosed with CHF. Ten of the 19 cats had narrowed
left-ventricular outflow tracts at the time enalapril
was initiated, while seven were assessed to have this
same echocardiographic feature three-to-six months
later.
Mean left-atrial size±standard deviation (SD) de-
creased significantly (from 1.8±0.3 cm to 1.6±0.4
cm; p of 0.01) [Table 1]. Interventricular septal
thickness±SD decreased significantly in both diastole
(from 0.7±0.2 to 0.6±0.1; p of 0.007) and systole
(from 1.0±0.2 to 0.9±0.1; p of 0.002), and the left-
ventricular free wall thickness±SD in diastole also
decreased significantly (from 0.8±0.2 to 0.7±0.2; p of
0.04) [Table 1]. The mean left-ventricular internal
dimension±SD in diastole also increased significantly
(1.4±0.3 to 1.5±0.2; p of 0.04) [Table 1]. There was
no correlation between the dose of enalapril and
changes in clinical or echocardiographic parameters.
No adverse side effects of enalapril were noted.
For all available blood pressure measurements at each
time point, the mean systolic blood pressure±SD was
131±25 mmHg at the time of initiation of enalapril
(n=15) and 139±30 mmHg when measured three-to-
40 JOURNAL of the American Animal Hospital Association
Table 2—Mean systolic blood pressure, serum creatinine con-
centration, and serum potassium concentration in cats at baseline
and follow-up evaluations.
* p of 0.05 or less compared to initial examination
six months later (n=6; p of 0.94) [Table 2]. If only
cats with blood pressure measurements at both time
points were analyzed, the initial mean systolic blood
pressure±SD was 137±33 mmHg, while the follow-up
mean systolic blood pressure±SD was 139±30 mmHg
(p of 0.94). Mean heart rate±SD was 188±25 beats
per minute at the initial evaluation and 192±30 beats
per minute at the follow-up evaluation (p of 0.63).
Mean serum creatinine concentration±SD decreased
significantly (from 1.60±0.36 mg/dl to 1.40±0.23 mg/dl; p
of 0.02) in the 15 cats that had renal profiles per-
formed at both time points [Table 2]. The mean serum
potassium concentration±SD increased significantly
(from 3.89±0.41 to 4.07±0.37 mEq/L; p of 0.05) in
these same 15 cats [Table 2]. No cat had a potassium
concentration above the reference range at either time
point.
At the time of this writing, the mean survival times
for these 19 cats are 1,174 days from the time of
diagnosis of HCM and 815 days from the time of
initiation of enalapril. Seventeen of the 19 cats still
are alive. In addition, the mean survival time for cats
that had CHF at the time of initiation of enalapril is
1,147 days, with nine of 11 cats still alive (the two
cats that died had survival times of 875 and 699 days,
respectively).
Discussion
Enalapril was well tolerated in these cats with HCM
and appeared to be beneficial in the treatment of
some cats with CHF. At baseline, 11 cats had CHF;
eight of these cats had persistent CHF despite treat-
ment with other medications. Congestive heart failure
was treated successfully after the addition of enalapril
in 10 of these 11 cats. Angiotensin-converting en-
zyme inhibitors have been used successfully in hu-
mans and in dogs for the treatment of CHF due to a
variety of conditions. 10,11 To this point, there have
been only anecdotal reports regarding the use of ACE
inhibitors in cats with CHF. The current study docu-
January/February 1998, Vol. 34
ments the usefulness of enalapril in the management
of CHF in some cats with HCM.
The use of vasodilators in humans with left-ven-
tricular outflow tract obstruction generally is thought
to be contraindicated.6 Vasodilators cause arteriolar
vasodilation and may, therefore, increase the vigor of
left-ventricular contraction, placing the interventricu-
lar septum and mitral valve in closer apposition. This
can worsen the left-ventricular outflow gradient and,
as the mitral valve is drawn into the left-ventricular
outflow tract, mitral regurgitation can increase. In
addition, the changes in the left-ventricular outflow
tract can lead to diminished cardiac output which can
result in symptomatic hypotension. Despite these con-
cerns, the authors were unable to identify any adverse
effects of enalapril in the 10 cats that had narrowing
of the left-ventricular outflow tract at the time of
initiation of enalapril treatment. Although it was an-
ticipated that blood pressure might decrease, blood
pressure was unchanged following treatment with
enalapril. Despite the fact that clinical improvement
was noted in cats treated with enalapril, the number
of cats with narrowing of the left-ventricular outflow
tract did not change significantly over time. This sug-
gests that the assumed outflow obstruction was not a
primary cause of the clinical signs in these cats. Con-
firmation of left-ventricular outflow obstruction, how-
ever, would require Doppler evaluation of the gradient
across the narrowed left-ventricular outflow tract.
Despite the fact that development of azotemia is a
recognized side effect of ACE inhibitors, this was not
a problem in the current study. Mean creatinine con-
centration actually decreased significantly. A study
in dogs with CHF showed that four of 10 dogs treated
with an ACE inhibitor, furosemide, digoxin, and a
sodium-restricted diet developed mild azotemia. 12 In
contrast, in a separate study on dogs with CHF, there
was no significant increase in the mean serum creati-
nine concentration in dogs treated with either enalapril
and furosemide or placebo and furosemide for the 28-
day study period. 11 Azotemia is most likely to result
in dogs with CHF when high doses of furosemide are
used. Therefore, it is recommended to use the lowest
possible dose of furosemide required to control clini-
cal signs of CHF.13 In the current study, cats were
given the lowest furosemide dose (mean dose±SD,
1.35±0.64 mg/kg body weight per day; range, 0.52 to
2.29 mg/kg body weight per day) necessary to pre-
vent fluid accumulation, and renal function typically
was assessed seven-to-10 days after initiating
enalapril.
Hyperkalemia also is a recognized side effect of
ACE inhibitor therapy in humans. In dogs, one study
found that 33% to 50% of normal dogs and 60% of
dogs with CHF treated with an ACE inhibitor, furo-
semide, digoxin, and a sodium-restricted diet devel-
January/February 1998, Vol. 34
oped mild hyperkalemia, although it was not signifi-
cant clinically. 12 This phenomenon has not been stud-
ied in cats with CHF, but enalapril in healthy cats was
shown to either promote or not change potassium
excretion. 14 In the current study, mean serum potas-
sium concentration increased significantly, although
the mean and individual concentrations remained
within the reference range. This suggests that, despite
the statistically significant rise in serum potassium,
there is little clinical significance to this finding.
Mean left-atrial size decreased significantly in this
group of cats. In addition, several measures of left-
ventricular hypertrophy improved after the cats were
started on enalapril. Mean interventricular septal
thickness in diastole and systole and left-ventricular
free wall thickness in diastole decreased significantly,
while the size of the left-ventricular chamber in dias-
tole increased. The data does not prove necessarily
that treatment with enalapril caused a reduction in
ventricular hypertrophy. Although these changes were
significant statistically, they may not account for the
possibility of variation in echocardiographic tech-
nique. In addition, the natural progression of HCM in
cats has not been well described, and changes in car-
diac dimensions may occur spontaneously over time.
Similarly, altered ventricular geometry might occur
as a result of changes in cardiac-loading conditions
which accompany either treatment or resolution of CHF.
The authors’ results differ from those published in
a study of human HCM which showed no improve-
ment in left-ventricular dimensions in patients taking
an ACE inhibitor compared to those taking a calcium
channel-blocker or β-antagonist. 15 The latter study,
however, used a low dosage of enalapril (range, 0.07
to 0.14 mg/kg body weight per day), whereas the
dosage used in cats in the current study would be
considered a high dose (range, 0.19 to 0.69 mg/kg
body weight per day) in human medicine. Previous
studies have found that enalapril reduced plasma ACE
activity by 95% in healthy cats using either a dosage
of 0.25 or 0.50 mg/kg body weight per day.14 Cur-
rently, a great deal of controversy exists regarding
the optimal dosage of ACE inhibitors in human pa-
tients with cardiac disease. Although small-scale tri-
als suggest that clinical improvements are correlated
positively with an increasing ACE inhibitor dose,
larger clinical trials (some of which currently are
underway) are needed for definitive answers. 16,17 In
the current study, no correlation was found between
clinical signs or echocardiographic changes and dos-
age of enalapril.
Several limitations in the current study are note-
worthy. The retrospective design did not allow for the
identification of an appropriate control group that did
not receive enalapril. In addition, it was not a blinded
study so there was the potential for investigator bias.
Enalapril 41
Finally, 17 of the 19 cats also were given medications
in addition to enalapril. This could be a confounding
factor in the improvements seen in some cats. Ran-
domized, double-blind, placebo-controlled studies are
needed to prove the efficacy of enalapril in feline
HCM. At this time, enalapril cannot be recommended
for routine use in uncomplicated cases. Nonetheless,
the preliminary data suggests that enalapril is well
tolerated, and it appears to improve clinical signs and
some echocardiographic parameters in cats with HCM.
a
Hitachi 747; Boehringer Mannheim Corp., Indianapolis, IN
References
1. Atkins C, Gallo A, Kurzman I, Cowen P. Risk factors, clinical signs, and
survival in cats with a clinical diagnosis of idiopathic hypertrophic
cardiomyopathy: 74 cases (1985–1989). J Am Vet Med Assoc
1992;201:613–8.
2. Sisson D, Thomas W. Myocardial diseases. In: Ettinger SJ, Feldman ED,
eds. Textbook of veterinary internal medicine. 4th ed. Philadelphia: WB
Saunders, 1995:995–1032.
3. Fox P. Evidence for or against efficacy of beta-blockers and aspirin for
management of feline cardiomyopathies. Vet Clin N Am Sm Anim Pract
1991;21:1011–22.
4. Bright J, Golden A, Gompf R, Walker M, Toal R. Evaluation of the
calcium channel-blocking agents diltiazem and verapamil for treatment
of feline hypertrophic cardiomyopathy. J Vet Int Med 1991;5:272–82.
5. Bonagura J, Stepien R, Lehmkuhl L. Acute effects of esmolol on left
ventricular outflow obstruction in cats with hypertrophic cardiomyopa-
thy: a Doppler-echocardiographic study. In: Proceed, 9th Am Coll Vet
Int Med Forum, 1991:878.
6. O’Gara P, DeSanctis R, Powell W. Hypertrophic cardiomyopathy. In:
Eagle KA, Haber E, DeSanctis RW, Austen WG, eds. Practice of cardi-
ology. 2nd ed. Boston: Little, Brown and Company, 1989:951–76.
7. Greenberg B, Quinones M, Koilpillai C, et al. Effects of long-term
enalapril therapy on cardiac structure and function in patients with left
ventricular dysfunction: results of the SOLVD echocardiography
substudy. Circulation 1995;91:2573–81.
8. Spinale F, Holzgrefe H, Mukherjee R, et al. Angiotensin-converting
enzyme inhibition and the progression of congestive cardiomyopathy.
Circulation 1995;92:562–78.
9. Sun Y, Ratajska A, Weber KT. Inhibition of angiotensin-converting
enzyme and attenuation of myocardial fibrosis by lisinopril in rats
receiving angiotensin II. J Lab Clin Med 1995;126:95–101.
10. SOLVD investigators. Effect of enalapril on survival in patients with
reduced left ventricular ejection fractions and congestive heart failure.
New Engl J Med 1991;325:293–302.
11. COVE study group. Controlled clinical evaluation of enalapril in dogs
with heart failure: results of the cooperative veterinary enalapril study
group. J Vet Int Med 1995;9:243–52.
12. Roudebush P, Allen T, Kuehn N, Magerkurth J, Bowers T. Effect of
combined therapy with captopril, furosemide, and a sodium-restricted
diet on serum electrolyte concentrations and renal function in normal
dogs and dogs with congestive heart failure. J Vet Int Med 1994;8:337–42.
13. Keene B, Rush J. Therapy of heart failure. In: Ettinger SJ, Feldman ED,
eds. Textbook of veterinary internal medicine. 4th ed. Philadelphia: WB
Saunders, 1995:867–92.
14. Sanders N, Hamlin R, Buffington T, Blaisdell J. Effects of enalapril on
healthy cats. In: Proceed, 10th Am Coll Vet Int Med Forum, 1992:822.
15. Hartmann A, Putz A, Hopf R. Effect of long-term ACE-inhibitor therapy
in hypertrophic cardiomyopathy (HCM). J Am Coll Cardiol
1995;25:234A.
16. Vagelos R, Nejedly M, Willson K, Yee YG, Fowler M. Comparison of
low versus high dose enalapril therapy for patients with severe conges-
tive heart failure (CHF). J Am Coll Cardiol 1991;17:275A.
17. Riegger GAJ. Effects of quinapril on exercise tolerance in patients with
mild to moderate heart failure. Eur Heart J 1991;12:705–11.
18. Moise NS. Echocardiography. In: Fox PR, ed. Canine and feline cardi-
ology. New York: Churchill Livingstone, 1988:113–56.
 Diagnosis of Shoulder Instability in
Dogs and Cats: A Retrospective Study
The glenohumeral joint is a remarkable articulation providing the greatest range of
motion of any joint in the body. Glenohumeral stability results from several
mechanisms, including those that do not require expenditure of energy by muscle
(“passive mechanisms”) and those that do (“active mechanisms”). Glenohumeral
instability has been recognized in 47 shoulders of 45 dogs and one cat. Cases are
presented because of chronic foreleg lameness. Shoulder joint pain is obviated by
the orthopedic examination. Only 57% of the involved shoulders presented with
degenerative joint disease. Signs of instability are recognized under anesthesia
using a craniocaudal or mediolateral drawer sign or both. This report describes the
radiographic and arthroscopic findings of shoulder instability. Arthroscopy of the
shoulder joint allows identification of all intra-articular pathologies. Shoulder
instability, not fully recognized in the past, appears to be the most common cause of
shoulder lameness in the dog. J Am Anim Hosp Assoc 1998;34:42–54.

J. F. Bardet, DVM, MS Introduction

O diagnostic “blind alley.” 1 “It is very difficult to make an exact diag-
From the Referral Surgical Practice,
32 rue Pierret,
92200 Neuilly-Sur Seine—France.
The shoulder joint is a common source of foreleg lameness. When
shoulder pain is elicited, many cases of foreleg lameness end up in a
nosis due to the lack of objective findings to reinforce the subjective
signs.”1 “Many cases are treated successfully based on a presumptive
diagnosis of tenosynovitis of the biceps tendon.” 1 Surprisingly, the
veterinary literature focused primarily on treatment of shoulder
luxations, 1–19 with only a few papers on the anatomy and biomechan-
ics of the canine shoulder joint. 9,20–22 Descriptions of shoulder
subluxations are anecdotal.23–27
In 1986, the first publication on arthroscopy of the canine shoulder
gave details of the technique, normal anatomy, and complications. 28
Several later papers have described the use of diagnostic arthroscopy
of the shoulder and arthroscopic surgery for the treatment of osteo-
chondritis dissecans (OCD) of the shoulder joint in dogs. 29–35
In human orthopedics, few topics have as broad an outline as the
treatment of the unstable shoulder. This subject has produced decades
of debate and over 250 surgical techniques. 36–39 The past decade has
produced many advances in the diagnosis and treatment of shoulder
instabilities including better anatomical studies, 40 which describe the
anatomy of stability as well as the pathophysiology of instability; the
use of magnetic resonance (MR) imaging to describe the multitude of
bony and soft-tissue lesions found in the unstable shoulder; 41 the
refinement of the medical history and the physical examination to
provide a more efficient diagnosis; and the use of the arthroscope to
finalize the pathoanatomic diagnosis and to treat the unstable shoul-
der.12–45 The evolution of open surgical techniques and postoperative
physiotherapy leads to a higher quality outcome on a predictable
basis.
The goals of this paper are to review the surgical anatomy and
biomechanics related to shoulder stability and to describe the diagno-

42 JOURNAL of the American Animal Hospital Association

January/February 1998, Vol. 34
Figure 1—Macroscopic view of an anatomical specimen of the
left shoulder joint showing the medial glenohumeral ligament
(MGHL). Note the (1) articular cartilage of the glenoid cavity, (2)
articular cartilage of the humeral head, (3) Y-shaped MGHL, and
(4) supraglenoid tubercle.
sis of shoulder instability, focusing mainly on
arthroscopic signs of instability.
Anatomy and Biomechanics of Glenohumeral
Stability
The glenohumeral joint is suited for mobility. The
large, spherical head of the humerus articulates with
the small, shallow glenoid fossa of the scapula. The
glenoid provides little coverage of the humeral head. 46
It has been suggested that glenohumeral stability re-
sults from a hierarchy of mechanisms, including those
that do not require the expenditure of energy by
muscle (“passive mechanisms”) and those that do
(“active mechanisms”).40 The shoulder joint is ca-
pable of movement in any direction, but its chief
movements are flexion and extension. 20,46
Passive Mechanisms
Muscle activity is not required to hold the shoulder
together. The intact shoulder of a fresh, anatomi-
cal specimen is quite stable. It appears appropriate
to discuss the “passive” mechanisms of the gleno-
Shoulder Instability 43
Figure 2—Macroscopic view of an anatomical specimen of the
left shoulder joint. Note the (1) articular cartilage of the glenoid
cavity, (2) articular cartilage of the humeral head, (3) medial
glenohumeral ligament (MGHL) which appears as a diagonal
band on the medial aspect of the joint, (4) biceps tendon, and (5)
tendon of insertion of the subscapularis muscle.
humeral joint which include ligamentous and cap-
sular restraints, joint conformity, glenoid labrum,
joint conformity, finite joint volume, and adhe-
sion/cohesion.
The glenohumeral ligaments can be identified on
the deep surface of the articular capsule on the medial
and lateral sides of the shoulder joint. 9,46 The medial
glenohumeral ligament (MGHL) appears either as a Y
shape [Figure 1] or a transverse band [Figures 2, 3].
The MGHL extends downward from the medial sur-
face of the supraglenoid tubercle of the scapula [Fig-
ure 3] across the shoulder joint to attach to the joint
capsule at the junction of the humeral neck and lesser
tubercule. 9 The caudal band of the ligament attaches
proximally (approximately 2 cm caudal to the cranial
band) on the medial side of the glenoid cavity. The
MGHL appears more often as a Y shape in large-
breed dogs. On arthroscopy from a lateral portal, the
MGHL appears most commonly as a transverse di-
agonal band on the medial side of the glenohumeral
joint [Figure 4]. The MGHL is visualized best when
the joint is distended. The distal humeral insertion is
located caudally in relation to the tendon of insertion
of the subscapularis muscle [Figure 5].
The lateral glenohumeral ligament (LGHL) extends
downward from the lateral rim of the glenoid cavity
to attach to the neck of the humerus and to the caudal
portion of the greater tubercle [Figure 6]. In large-
breed dogs, the ligament is approximately 2 cm wide
at its proximal insertion and 1.5 cm wide at its hu-
meral attachment. 9 Seen from either a medial or a
caudolateral portal on arthroscopy, the LGHL ap-
pears as a wide ligament on the craniolateral aspect of
the glenohumeral joint [Figure 7].
The medial and lateral glenohumeral ligaments ap-
pear as relatively wide structures with strands of fi-
bers that invaginate in the joint cavity from the
44 JOURNAL of the American Animal Hospital Association January/February 1998, Vol. 34

Figure 5—Arthroscopic view of the craniomedial aspect of the

left shoulder joint from a lateral portal. Note the (1) articular
cartilage of the glenoid cavity, (2) articular cartilage of the
humeral head, (3) medial glenohumeral ligament (MGHL) which
appears as a diagonal band on the medial aspect of the joint, (4)
biceps tendon, and (5) tendon of insertion of the subscapularis
muscle.

Figure 3—Detailed macroscopic view of the craniomedial as-

pect of the left shoulder. Note the (1) articular cartilage of the
glenoid cavity, (2) articular cartilage of the humeral head, (3)
medial glenohumeral ligament (MGHL) which appears as a
diagonal band on the medial aspect of the joint, (4) biceps
tendon, (5) tendon of insertion of the subscapularis muscle, and
(6) supraglenoid tubercle.
Figure 6—Macroscopic view from an anatomical specimen of
the craniolateral aspect of the shoulder. Note the (1) articular
cartilage of the humeral head, (2) biceps tendon, (3) bicipital
groove, (4) lateral glenohumeral ligament (LGHL), and (5) joint
capsule.

Figure 4—Arthroscopic view of the medial aspect of the left

shoulder joint from a lateral portal. Note the (1) articular carti-
lage of the glenoid cavity, (2) articular cartilage of the humeral
head, and (3) medial glenohumeral ligament (MGHL) which
appears as a diagonal band on the medial aspect of the joint.
Figure 7—Arthroscopic view of the lateral glenohumeral liga-
ment (LGHL). Note the (1) LGHL and (2) articular cartilage of the
humeral head.
January/February 1998, Vol. 34
Figure 8—Macroscopic view from an anatomical specimen of
the glenoid cavity and capsuloligamentous restraints of the left
shoulder. Note the (1) glenoid cavity, (2) biceps tendon, (3)
medial glenohumeral ligament (MGHL), (4) caudomedial joint
capsule, and (5) lateral joint capsule.
Figure 9—Macroscopic view from an anatomical specimen of
the glenoid cavity and capsuloligamentous restraints of the left
shoulder as seen in Figure 8. Note the (1) glenoid cavity, (2)
biceps tendon, (3) medial glenohumeral ligament (MGHL), (4)
caudomedial joint capsule, (5) lateral joint capsule, and (6)
scalpel handle introduced into the capsular recess.
capsule so that the inner and outer surfaces of the
ligaments are covered with synovial membranes. 9
The articular joint capsule forms a loose sleeve
which attaches proximally at the periphery of the
glenoid cavity on the cranial, lateral, and caudal as-
pects [Figure 8]. On the medial margin, the joint
capsule attaches more proximally several millimeters
away from the glenoid rim, forming a synovial recess
[Figures 9, 10]; on the humeral neck, it attaches sev-
eral millimeters distal to the articular aspect of the
humeral head, where it blends with the periosteum on
the neck of the humerus. Part of the joint capsule
surrounds the tendon of origin of the biceps brachii
muscle and extends distally about 2 cm in the intertu-
bercular groove [Figures 3, 11]. Medially, the capsule
is attached loosely to the tendons of the subscapularis
and coracobrachialis muscles and laterally to the ten-
dons of the infraspinatus and teres minor muscles.
These tendons can be separated carefully from the
capsule without entering the joint.
Shoulder Instability 45
Figure 10—Macroscopic view from an anatomical specimen of
the medial aspect of the left glenoid cavity. Note the (1) glenoid
cavity, (2) biceps tendon, (3) medial glenohumeral ligament
(MGHL), (4) caudomedial joint capsule, and (5) medial free
margin of the glenoid cavity. The joint capsule inserts on the
scapular neck.
Figure 11—Arthroscopic view of the biceps tendon and bicipital
groove of the right shoulder joint. Note the (1) cranial surface of
the articular cartilage of the humeral head, (2) biceps tendon,
and (3) bicipital groove.
Until recently, it was agreed that the insertions of
the “cuff muscles” were responsible for maintaining
joint integrity. 23 More recently it has been shown that
the joint capsule and collateral ligaments of the gle-
nohumeral joints play significant roles in stability. 9,21
An in vitro study revealed that cutting the tendons of
the “cuff muscles” results in minimal loss of stability.
Stability is decreased substantially by transecting the
capsule and collateral ligaments. 21 The humeral joint
is not luxated easily when the collateral ligaments are
intact. 21
Other contributing mechanisms to stability are con-
cavity and compression. 47 The depth of the bony gle-
noid is enhanced by the articular cartilage and the
glenoid labrum when present. The concavity and the
fit of the glenoid to the humeral head provide stabil-
ity to the joint, which is enhanced by forces pressing
the ball into the socket 47 (see Active Mechanisms).
46 JOURNAL of the American Animal Hospital Association
Figure 12—Macroscopic view from an anatomical specimen of
the right glenoid cavity and periarticular labrum. Note the (1)
glenoid cavity, (2) biceps tendon, (3) medial capsular recess, (4)
caudolateral labrum, and (5) caudolateral joint capsule.
The glenoid labrum is a fibrous rim that serves to
deepen the glenoid fossa and allow attachment of the
glenohumeral ligaments and the biceps tendon to the
glenoid in humans.47 It is the interconnection of the
glenoid periosteum, bone, articular cartilage, syno-
vium, and joint capsule. This labrum is described in
dogs;9,23,46 however, the authors only identified it
macroscopically in one of the 12 cadaver specimens
used for the anatomical study of the shoulder joint
[Figure 12]. The labrum is described as fibrocartilage
that extends 1-to-2 mm beyond the edge of the gle-
noid cavity caudolaterally.46 It may appear as the
proximal insertion of the biceps tendon [Figure 13],
but in most cases there is no macroscopic transitional
structure at the insertion of the joint capsule on the
glenoid rim [Figure 14]. Therefore, the stabilizing
role of the labrum in the dog appears limited.
Anatomical studies, surgical findings, attempts at
aspiration, and MR images confirm that there is mini-
mal (less than 1 ml) free fluid in the normal shoulder
joint.47 The normal shoulder is sealed by the capsule.
Thus, like the syringe, the shoulder joint is stabilized
by its limited joint volume. As long as the joint is a
closed space containing minimal free fluid, the joint
surfaces cannot be distracted easily or subluxated.
Small translations of the humerus on the glenoid can
be balanced by fluid flow in the opposite direction,
allowing a nonuniform gap to open in the joint space.
This gap can increase until all available fluid has
been mobilized, at which point further motion of the
joint is resisted by negative fluid pressure in the joint.
This negative pressure pulls the capsule inward to-
ward the joint space, putting its fibers “on the stretch.”
This mechanism is aided by the fact that intraarticular
pressure normally is slightly negative.49
The stabilization mechanism changes when the gap
between the articular surfaces becomes very small.
Viscous and intermolecular forces begin to dominate,
preventing ready fluid motion and providing a cohe-
January/February 1998, Vol. 34
Figure 13—Arthroscopic view of the biceps tendon of the left
shoulder. Note the (1) supraglenoid tubercle, (2) cranial border
of the articular cartilage of the humeral head, (3) biceps tendon,
and (4) glenoid labrum.
sive bond between the glenoid and humerus. This is
termed the “adhesion-cohesion mechanism.” 47 A fa-
miliar example is provided by two wet microscope
slides pressed together. Water is held to their surfaces
by adhesion. They readily can slide on each other but
cannot be pulled apart easily by forces applied at
right angles to their flat surfaces, because the water
holds them together by cohesion. Joint surfaces are
wet with joint fluid that holds them together by adhe-
sion/cohesion as well. This joint fluid interface has
the very desirable properties of high tensile strength
(i.e., surfaces are difficult to pull apart), and little
shear strength (i.e., the interface allows sliding of the
two joint surfaces on each other with low resistance).
An important distinction is that the adhesion/cohe-
sion mechanism does not put the capsular fibers on
the stretch, as viscous forces suffice to prevent fluid
from entering the joint space. Thus, stability is pro-
vided entirely by forces exerted by and on the articu-
lar surfaces.
Both the effects of limited joint volume and adhe-
sion/cohesion would be reduced or eliminated by the
addition of excess fluid (gas or liquid) to the joint or
when the joint is inflamed. This phenomenon was
well described by Humphry in 1858.47
Active Mechanisms
Dynamic glenohumeral stability in humans is pro-
vided by the biceps and the subscapularis, supraspina-
tus, infraspinatus, and teres minor muscles of the
rotator cuff. The cuff muscles serve several stabiliz-
ing functions. First, by virtue of the blending of their
tendons with the glenohumeral capsule and ligaments,
selective contraction of the cuff muscles can adjust
the tension in these structures, producing “dynamic”
ligaments, as proposed by Cleland in 1866. 47 Second,
January/February 1998, Vol. 34 Shoulder Instability 47

Table 1
Breeds of the 45 Dogs Diagnosed with Shoulder Instability

Brittany 6 Cavalier King Charles spaniel 1

French poodle 5 Pyrenees Mountain dog 1
Labrador retriever 5 English springer spaniel 1
Doberman pinscher 4 Irish setter 1
Mixed-breed dog 3 Boxer 1
Greyhound 3 German shepherd dog 1
Rottweiler 2 Cocker spaniel 1
Whippet 2 Standard schnauzer 1
Dogue of Bordeaux 1 Braque 1
Napolitan 1 Dachshund 1
Dalmatian 1 Afghan hound 1
Drakar 1

by contracting together, they press the humeral head
into the glenoid fossa, locking it into position and
thus providing a secure scapulohumeral link for fore-
limb function. Third, by contracting selectively, the
rotator cuff muscles can resist displacing forces re-
sulting from contraction of the principal shoulder
muscles.
Materials and Methods
Forty-seven shoulder joints were examined in 45 dogs
and one cat between September 1, 1993 and March
31, 1996 because of foreleg lameness and shoulder
instability. The history included the breed, age, sex,
weight, onset and duration of clinical signs, progres-
sion of signs, activity of the animal, prior medical treat-
ment, and influence of activity. Ages of dogs ranged
from 18 months to 13 years (mean, 5.3 years). There
were 30 males and 16 females. Among the 45 dogs, 23
breeds were represented including Brittany (n=6),
French poodle (n=5), Labrador retriever (n=5), and Do-
berman pinscher (n=4) [Table 1]. Only one dog (2.2%)
had bilateral involvement. Before entering the study,
each case underwent complete physical and orthopedic
examinations. In two patients, clinical signs initially
were attributed to cervical disk disease. A myelographic
examination was performed first, followed by an elec-
tromyography and nerve conduction velocities.
When the cause of lameness was located, the or-
thopedic examination included range of motion, pres-
ence of pain in hyperextension, biceps tendon test,
and palpation to assess joint instability. Each animal
was anesthetized, and the same orthopedic examina-
tion was repeated. Mediolateral, craniocaudal, and
stress mediolateral radiographs were taken of each
shoulder. The preoperative radiographic status of os-
teoarthritis involving the shoulder joint was graded
as absent, minimal (i.e., osteophytes less than 2 mm),
moderate (i.e., osteophytes 2-to-4 mm), or severe (i.e.,
osteophytes greater than 4 mm). Following radiogra-
phy, an arthroscopy of the affected joint was per-
formed prior to any treatment.
Arthroscopic examination was performed with a
2.7-mm 30˚ foreoblique arthroscope with a 3.5-mm,
outside-diameter sleeve. Light was supplied by a xe-
non source. The arthroscopic procedure was visual-
ized on a monitor using a camera. Photographic
documentation was made with a color printer. Each
patient was positioned in lateral recumbency and the
leg was prepared aseptically. The joint was distended
with 10-to-15 ml of lactated Ringer’s solution after
being punctured with a 19-gauge needle craniolater-
ally between the acromion and caudal part of the
greater tubercule in a caudomedial direction. A stab
incision was made 1 cm caudally and 1 cm distally to
the acromion 28 using a no. 11 Bard-Parker scalpel
blade. The joint capsule then was penetrated using
the blunt trocar locked in the arthroscopic sleeve. The
trocar was replaced by the arthroscope, and the light
cable and the camera and inflow lines were connected.
Joint inspection then could be performed. Fluid in-
flow was maintained via a sterile infusion set con-
nected to the stopcock of the trocar sleeve. Fluid
leaving the outflow canula was drained away via a
silastic tube. 21
With the arthroscope in the lateral portal, a sys-
tematic arthroscopic examination is carried out with
inspection of the synovium, articular cartilage sur-
faces, glenohumeral ligaments, labrum, tendon of the
biceps muscle, tendon of the subscapularis muscle,
and joint capsule.
Results
Each dog and the cat were presented because of
chronic foreleg lameness. Most had been lame for
48 JOURNAL of the American Animal Hospital Association January/February 1998, Vol. 34

Table 2 Table 4
Clinical Signs of Shoulder Subluxation Arthroscopic Findings in
47 Unstable Shoulders
Signs No. of Cases
Chronic foreleg lameness Arthroscopic Findings No. of Cases
Permanent* 36 Normal shoulder 15
Intermittent 10
Synovium
Atrophy of the shoulder muscles 15 Minimal synovitis 10
Nonweight-bearing lameness 6 Moderate synovitis 5
Spontaneous cries 5 Severe synovitis 13
Fibrous synovitis 4
“Disk disease” 5
Articular cartilage of the glenoid cavity
“Wobbler syndrome” walk 1 Erosion of medial ridge 22
Jumping from stairs 1 Eburnation 8
Osteophytes 8
* Continual lameness; nonresponsive to nonsteroidal Fractures of caudal rim 2
anti-inflammatory drug treatment Articular cartilage of the humeral head
Superficial erosion of caudal 25
articular cartilage
Eburnation 11
Table 3 Osteophytes 11
Preoperative Radiographic Examination of Medial glenohumeral ligament (MGHL)
47 Unstable Shoulders Distended 20
Torn 8
Thickening of the branch of the MGHL 3
No. of
Caudolateral labral tear 5
Radiographic Findings Cases Percentage
Tendon of the biceps muscle
No degenerative joint 20 43 Tendonitis 1
disease Partial tear 3
Degenerative joint Bipartite 1
disease Tendon of the subscapularis muscle
Minimal 10 21 Tendonitis 3
(osteophytes less Tear 2
than 2 mm) Ballooning joint capsule 3
Moderate 5 11
(osteophytes 2 to
4 mm)
high stairs and landing on all four legs. This case had
Severe 12 26 bilateral shoulder involvement. Atrophy of the shoul-
(osteophytes greater
than 4 mm) der muscles was obvious in 15 dogs. The clinical
signs are summarized in Table 2.
Supraspinatus muscle 5 11
calcification All dogs except one had pain on shoulder hyperex-
Medial osseous defect of 3 6 tension. The biceps tendon test, with the front limb in
humeral head full extension, along with the thorax test were posi-
tive in 40 shoulders. In five shoulders, the sublux-
ation was recognized without anesthesia during the
more than two months and some for several years. biceps tendon test.
The lameness was permanent (i.e., continual and nonre- A preoperative radiographic examination was per-
sponsive to nonsteroidal anti-inflammatory drug formed for each shoulder. Normal shoulders were
[NSAID] treatment) in 35 dogs and one cat and inter- identified in 20 (43%) cases [Table 3]. Osteoarthritis
mittent in 10 dogs. Five dogs and the cat had was observed in 27 (57%) cases. Osteoarthritis was
nonweight-bearing lamenesses. Five dogs were cry- classified as minimal in 10 (21%) cases and severe in
ing spontaneously because of pain and were referred 12 (26%) cases. A medial osseous defect was ob-
for cervical disk disease; two of these five were re- served on the craniocaudal views of the humeral head
ferred for tetraplegia. One of these five, a Brittany, in five (11%) dogs, and calcification of the tendon of
presented for evaluation of cervical disk disease, it the supraspinatus muscle was obvious in five (11%)
was walking as if it had wobbler syndrome, was un- more cases. The medial rim of the glenoid cavity
able to go downstairs, and was jumping from 1.5 m- appeared flattened in three cases.
January/February 1998, Vol. 34
Figure 14—Arthroscopic view of the caudal margin of the gle-
noid cavity. Note the (1) articular cartilage of the glenoid cavity,
(2) joint capsule, and the absence of an obvious labrum.
Figure 15—Arthroscopic view of the left shoulder showing a
severe synovitis associated with shoulder instability. Note the
(1) articular cartilage of the glenoid cavity, (2) articular cartilage
of the humeral head, (3) medial glenohumeral ligament (MGHL)
which appears as a diagonal band on the medial aspect of the
shoulder, and (4) severe synovitis with pendulous villi.
Upon arthroscopic examination, the synovial mem-
brane was normal in 15 of the 47 shoulders [Table 4].
In the remaining 32 shoulders, synovitis was graded
as minimal (n=10), moderate (n=5), severe (n=13)
[Figure 15], and fibrous (n=4). Abnormalities of the
articular cartilage were observed on the glenoid cav-
ity and on the humeral head. The most common find-
ing on the glenoid cavity was an erosion of the medial
rim (n=22) [Figure 16]. The articular cartilage of the
glenoid cavity was eburnated (n=8); eburnation always
was associated with osteophyte formation on the cau-
dal rim of the glenoid cavity. The most common ar-
ticular cartilage defect was located on the caudal
articular cartilage of the humeral head in 25 shoul-
ders [Figure 17]. Eburnation of the humeral head was
associated with osteophyte formation in 11 shoulders.
In three patients, the osseous defect seen on the
Shoulder Instability 49
Figure 16—Arthroscopic view of the left shoulder showing
erosions of the medial margin of the glenoid cavity. Note the (1)
articular cartilage of the glenoid cavity, (2) articular cartilage of
the humeral head, (3) medial glenohumeral ligament (MGHL)
which appears as a diagonal band on the medial aspect of the
shoulder, and (4) severe synovitis with pendulous villi.
Figure 17—Arthroscopic view of the caudal aspect of the right
shoulder showing erosion of the caudal articular surface of the
humeral head. Note the (1) caudal margin of the glenoid cavity,
(2) caudal articular surface of the humeral head, and (3) joint
capsule.
craniocaudal radiographs was observed during the
arthroscopic examination.
After assessing the synovium and articular carti-
lage, the evaluation of the glenohumeral ligaments
was carried out. The medial glenohumeral ligament
(MGHL) either was distended [Figures 18A, 18B]
and frayed (n=20) [Figures 19, 20] or torn (n=8) [Fig-
ures 21, 22]. In three cases, only the caudal part of the
MGHL was thickened [Figure 23]. If no lesion was
identified in the MGHL, the lateral and caudolateral
labrum was inspected. It was found detached in five
shoulders [Figure 24].
After assessing the biceps anchor, the biceps is
followed out to its exit point in the bicipital groove.
The biceps tendon was torn partially in three cases
50 JOURNAL of the American Animal Hospital Association
Figure 18A
Figure 18B
Figures 18A, 18B—Arthroscopic view of the right shoulder
showing a distended, incompetent medial glenohumeral liga-
ment (MGHL). (A) Note the (1) glenoid cavity, (2) humeral head,
(3) distended MGHL, and (4) joint capsule. (B) Note the (1)
glenoid cavity, (2) humeral head, (3) distended MGHL, and (4)
an egress cannula probing the incompetent MGHL.
and bipartite in one case. In one shoulder, a severe
tendonitis without rupture was observed. The tendon
of insertion of the subscapularis muscle was torn in
two cases [Figure 25]; a tendonitis of the same tendon
was seen in three instances.
The arthroscopist should be familiar with capsular
volume. The caudal axillary recess was capacious and
did not tighten with appropriate changes in leg posi-
tion, suggesting the possibility of a plastically de-
formed capsule secondary to microtrauma [Table 4]
in three shoulders.
Discussion
Shoulder instability appears to be a common cause of
lameness in dogs, affecting mainly medium- and
large-breed dogs. Most affected dogs are hyperactive.
January/February 1998, Vol. 34
Figure 19—Arthroscopic view of a frayed medial glenohumeral
ligament (MGHL) in the left shoulder. Note the (1) articular
cartilage of the glenoid cavity, (2) articular cartilage of the
humeral head, and (3) MGHL. The MGHL is torn partially.
Figure 20—Arthroscopic view of a frayed medial glenohumeral
ligament (MGHL) in the right shoulder. Note the (1) articular
cartilage of the glenoid cavity, (2) articular cartilage of the
humeral head, (3) MGHL, and (4) an egress cannula probing the
dilacerated MGHL.
The Brittany, French poodle, and Labrador retriever
appear overrepresented. Shoulder instability is much
more common than luxations since only nine dogs
were treated for shoulder luxations during the same
period. The most common clinical presentation is a
permanent foreleg lameness. It should be differenti-
ated from spinal disorders since five cases were re-
ferred because of neurological disorders.
Pain on hyperextension was present in almost ev-
ery case, and the biceps tendon test was positive in 40
(85%) of 47 unstable shoulders. The biceps tendon
test appears to be more an indicator of shoulder joint
pain than a pathognomonic sign of biceps tendon
disorders. In five shoulders, subluxations were recog-
nized preoperatively without anesthesia. Having
learned to diagnose shoulder instability initially by
arthroscopy, a clinical test of palpation under anes-
January/February 1998, Vol. 34
Figure 21—Arthroscopic view of a torn medial glenohumeral
ligament (MGHL) in the right shoulder. Note the (1) articular
cartilage of the glenoid cavity, (2) articular cartilage of the
humeral head, and (3) MGHL.
Figure 22—Arthroscopic view of the medial aspect of the left
shoulder. The medial glenohumeral ligament (MGHL) is absent.
Note the (1) articular cartilage of the glenoid cavity, (2) articular
cartilage of the humeral head, (3) medial joint capsule, and (4)
an egress cannula probing the distended joint capsule.
thesia was developed to detect shoulder subluxations.
It may be compared with the drawer sign for the stifle
joint. Both shoulders should be compared in the same
individual. It is mandatory to use bony landmarks of
the scapula and humerus. The scapula is held in one
hand with the thumb on the acromion and the index
finger wrapped around the craniomedial side of the
scapular neck. The other hand holds the humerus with
the thumb on the caudolateral aspect of the proximal
humeral metaphysis and the index finger on the
greater tubercule. Translocation of the humeral head
in the cranial, medial, caudal, and lateral directions is
determined with the shoulder in a semiflexed posi-
tion. A craniocaudal or mediolateral drawer sign may
be elicited. The direction and importance of the sub-
luxation must be recorded. The degree of transloca-
tion may be classified as none or absent (i.e., Grade
Shoulder Instability 51
Figure 23—Arthroscopic view of the medial aspect of the right
shoulder showing the thickening of the caudal branch of the
medial glenohumeral ligament (MGHL). Note the (1) glenoid
cavity, (2) humeral head, and (3) thickened caudal branch of the
MGHL.
Figure 24—Arthroscopic view of the detached labrum and joint
capsule from the lateral aspect of the right shoulder. Note the (1)
lateral margin of the glenoid cavity, (2) humeral head, (3)
detached labrum and joint capsule, and (4) an egress cannula
probing the lateral joint capsule tear.
1) when translocation of the head of the humerus on
the glenohumeral joint is not appreciated; as mild
(i.e., Grade 2) when some translocation is appreciated
but is not enough to allow the head of the humerus to
rise up on the rim of the glenoid cavity; as moderate
(i.e., Grade 3) when the head of the humerus is appre-
ciated to move up on the rim of the glenoid cavity;
and as severe (i.e., Grade 4) when the head of the
humerus courses over the rim of the glenoid cavity
and is dislocated. 50
Degenerative joint disease (DJD) was present in
57% of the cases. Degenerative joint disease was
minimal in 21% of the unstable shoulders; the first
sign was a small osteophyte on the caudal margin of
the humeral head on the mediolateral radiograph.
When DJD is apparent on the radiographs and occurs
in the absence of OCD, instability of the shoulder
52 JOURNAL of the American Animal Hospital Association
Figure 25—Arthroscopic view of the craniomedial aspect of the
left shoulder joint showing the torn insertion of the subscapularis
muscle tendon. Note the (1) biceps tendon, (2) humeral head,
(3) torn subscapularis muscle tendon, and (4) joint capsule.
joint should be suspected strongly. However, the ab-
sence of DJD cannot exclude instability since 43% of
the unstable shoulders did not show any signs of
DJD. Other means of diagnosis are most helpful for
the early diagnosis of shoulder instability.
Shoulder instability in humans typically is diag-
nosed and classified on the basis of history, physical
examination, and plain radiographs. Classification of
the instability is of considerable importance because
surgical treatment varies with the direction of the
instability. Special diagnostic tests are available in
human medicine. They include stress examination,
tomographic or computed tomographic arthrography,
ultrasonography, MR imaging, shoulder arthroscopy,
and exploratory arthrotomy. 41,51 Plain film radio-
graphs primarily assess the alignment and integrity of
the osseous structures. Ultrasonography has been ad-
vocated for the detection of rotator cuff tears, whereas
computed tomography (CT) after the injection of
intraarticular contrast has been used in the detection
of injuries to the osseous or labral-capsular compo-
nents. 50 The most recent modality to be employed is
MR imaging, a technique that combines excellent soft-
tissue contrast and multiplanar capabilities without
the use of ionizing radiation. 41,50 However, these tech-
niques are not readily available in most veterinary
hospitals, or the techniques are not described. None
of the tests are effective for assessing abnormalities
of the joint capsule, nor can they assess the compe-
tency of the capsule and its ligamentous structures in
preventing translocation of the head of the humerus
on the glenoid cavity. Shoulder arthroscopy appears
effective for identifying impression lesions of the
head of the humerus and glenoid margins and for
assessing the volume and relative laxity of the cap-
sule, anomalies of the synovium, and lesions of the
glenohumeral ligament, biceps tendons, and labrum.
January/February 1998, Vol. 34
The glenohumeral joint is a remarkable articula-
tion, providing the greatest range of motion of any
joint in the body. In contrast to the acetabulum of the
hip joint, the glenoid does not provide an instrinsically
stable socket. Capsuloligamentous constraints pro-
vide a critical contribution to glenohumeral joint sta-
bility.21,37,51 The concept of concavity compression
refers to the stability afforded a convex object that is
pressed into a concave surface. For example, pressing
a round ball onto a flat table top provides little resis-
tance to a counter pressure trying to slide the ball
across the table’s surface. If the ball is pressed into a
concavity on the table top, the stability of the ball is
enhanced by the depth of the concavity and by the
magnitude of the compressive force. The glenoid ar-
ticular geometry may seem too shallow to provide
significant constraint for the humeral head. Although
the glenoid fossa is only one-fourth the size of the
humeral articular surface, it does provide a concav-
ity. 51 Stability attributed to concavity compression is
compromised if the glenoid is small or flat, if the
labrum is torn or avulsed, or when the concavity is
lessened by injury or wear as observed radiographi-
cally in three cases. Recurrent instability episodes
would tend to erode the articular cartilage of the
medial glenoid rim and further lessen the concavity.
Perhaps relative flatness of the glenoid articular sur-
face (i.e., lack of effective glenoid depth) could pre-
dispose these patients to abnormal subluxations.
Simple observation suggests that the harder the
humeral head is compressed into the glenoid concav-
ity, the more stable the glenohumeral joint is to ap-
plied translating forces. The various shoulder muscles
provide the dynamic compression of the humeral head
into the glenoid concavity in vivo. Other potential
causes of subluxations related to an abnormal con-
cavity compression include muscle imbalance, creat-
ing a net force that deviates excessively from the
glenoid center, or abnormal position of the humeral
head due glenoid version.
High-demand, repetitive use of the shoulder also
has been implicated in the etiology of glenohumeral
instability. Historically, shoulder dislocations had
been classified as either “traumatic” or “atraumatic.”
Shoulders were thought to become unstable either on
the basis of a major traumatic injury or multiple small
traumas. Repetitive microtrauma has been implicated
as an etiology of shoulder instability, mainly in ath-
letes who use their arms to throw objects. 52 If these
stresses are applied at a rate that is greater than the
rate of tissue repair, these repetitive insults can pro-
duce damage to the tissues. It is well accepted that if
a material is subjected to a large number of loading
cycles, it will fail at a stress lower than its ultimate
tensile stress. It is quite possible that the repetitive,
high-velocity motions of the shoulder may cause fa-
January/February 1998, Vol. 34
tigue failure to the fibers of the glenohumeral liga-
ments because the endurance limit is exceeded during
these motions. 52 It has been shown that a ligament
undergoes significant stretching before ultimate fail-
ure when it is tested in uniaxial tension. 52 It is sus-
pected that the high-demand, repetitive loading of
certain shoulders may lead to fatigue failure of the
ligament, resulting in stretching of the ligament and
impairment of the proprioceptive function of the cap-
sule. Indeed, axonal fibers of different diameters have
been identified in the glenohumeral ligaments, sug-
gesting a proprioceptive role for these ligaments. 53
Moreover, differences have been demonstrated in
shoulder proprioception between stable shoulders and
unstable shoulders before and after repair.52
In 31 (66%) of 47 cases, the MGHL either was
distended (i.e., incompetent), torn, or thickened; in
five (11%) cases, there was a tear of the caudolateral
labrum. The severity of the MGHL lesions appeared
to be related to the degree of DJD. When the MGHL
was torn, in two instances the tendon of insertion of
the subscapularis muscle also was torn, the shoulder
joint was severely osteoarthritic with eburnation and
an associated fibrous synovitis. Changes related to
aging in soft tissues of the shoulder may represent a
complex situation in which two independent factors
(i.e., chronological aging and activity-induced wear-
and-tear effects) might contribute in equally signifi-
cant ways to the development of the pathologies. 54
Aging is associated with important structural, bio-
chemical, and biomechanical changes in the tendon. 55
The collagen content of a tendon remains fairly con-
stant throughout maturity and seems to decrease
slowly with age. 53 In old rabbits, multiple morpho-
logical and biochemical changes occur in the Achilles
tendon which are attributed to aging. 54 In older hu-
mans, the supraspinatus tendon shows a progressive
loss in integrity with marked fiber disorganization. 54
Aging may be a contributing factor of shoulder insta-
bility in dogs; however, not every old dog has un-
stable shoulders even if many have DJD of the
shoulder without clinical signs. 56 Many younger dogs
(mean age, 5.3 years) have unstable shoulders.
It also has been shown that dogs suffering from hip
dysplasia may suffer from shoulder DJD three-to-
four years after the clinical manifestations of hip dys-
plasia. 56 Several joints appear involved by DJD.
Genetic factors may be suspected as in hip dysplasia.
Joint instability has been recognized as a cause of
DJD. The phenomenon of joint laxity and instability,
leading to altered contact stresses and contact areas,
has been well documented. 56,57 The exact role of re-
petitive trauma on articular cartilage has been ques-
tioned. Repetitive loading appears to be a factor in
the development of the osteoarthritis of the gleno-
humeral joint. 52,58 Many shoulders are subject to re-
Shoulder Instability 53
petitive stresses, but only a small percentage of cases
develop clinical signs.
Finally, the instability of the shoulder joint should
be differentiated from the tenosynovitis of the biceps
tendon, 1 mineralization of the supraspinatus ten-
don, 59,60 calcifying tendinopathy of the biceps brachii
muscle, 61 and rupture of the biceps brachii tendon.1
Tenosynovitis of the biceps tendon was a disease of
the 1940s and 1950s in the human medical litera-
ture. 62 The number of diagnosed cases has decreased
dramatically over the decades because of the improve-
ment in the knowledge of the anatomy, biomechanics,
and diagnostic imaging of the shoulder joint. During
this study, the author found only one case of teno-
synovitis of the biceps tendon. 63 Arthroscopy offers
the advantage of recognizing all the intraarticular pa-
thologies. Most of these pathologies are recognized
today because of the magnification offered by new
arthroscopic means and were not recognized in the
past, even after exploratory arthrotomy of the shoul-
der joint. Mineralization of the supraspinatous tendon
and calcifying tendinopathy may be suspected if all
the other intraarticular causes of lameness have been
eliminated by arthroscopy.
Conclusion
Shoulder instability was found to be the most com-
mon cause of shoulder lameness in medium- and
large-breed adult dogs. The patients were presented
for chronic foreleg lameness. Pain was elicited on
hyperextension of the shoulder joint. Of affected
shoulder joints, 57% showed signs of DJD. Palpation
of these shoulders under anesthesia revealed a
craniocaudal or mediolateral drawer sign or both.
Arthroscopy was most helpful in detecting signs of
instability.
a
Karl STORZ Veterinary Endoscope; Tuttlingen, Germany
b
Olympus France; Scope, Rungis, France
c
OTV-S3 Olympus camera; Scope, Rungis, France
d
Sony color printer manigraph; Sony, Paris, France
e
U-Matic videocassette recorder VO-7630; Sony, Paris, France
f
Digivideo-system Karl Storz; Tuttlingen, Germany
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 The Canine Intervertebral Disk
Part One: Structure and Function
Intervertebral disk disease continues to be a common and debilitating condition of
dogs. In the first of a two-part article on the canine intervertebral disk, the
microscopic and ultrastructural anatomy of the normal, nonchondrodystrophoid disk
is described. Specific attention is placed on elements of the structure which impart
important functional attributes. Finally, the role of the intervertebral disk in providing
flexibility to the vertebral column is discussed, with a description of its biomechanical
properties and reaction to compressive loads. J Am Anim Hosp Assoc 1998;34:55–63.

Jonathan P. Bray, MVSc, Introduction

CertSAS, MACVSc, MRCVS,
Diplomate ECVS
Hilary M. Burbidge, BVSc, MVSc,
DVR, FACVSc, MRCVS
R climbed annually during a 10-year period.3 These increases may be
From the Department of Veterinary
Clinical Science,
Massey University,
Palmerston North, New Zealand.
Doctor Bray’s current address is
71a Millen Avenue,
Pakuranga, Auckland, New Zealand.
Intervertebral disk disease is a common, frequently debilitating and
painful disease. Although current figures on its incidence are not
available, some evidence indicates that the disease is becoming more
prevalent in the dog. Over 40 years ago, disk-related disease ac-
counted for 0% to 1% of clinical patients; 1 this incidence apparently
had increased to 2.3% by the 1970s.2 In one study, the frequency of
disk-related problems in dogs which required veterinary attention
attributed to improved recognition of the disease by veterinarians,
changes in breed popularity during this time, and a more aged popula-
tion due to improvements in health care overall.
Initial descriptions of intervertebral disk herniation in humans first
were reported in 1824. 4 The origin of the bulging, compressive tissue
within the neural canal at first was not appreciated, and the lesion was
considered to be neoplastic in nature. Eventually, in 1932, Mixter and
Barr 5 identified the true nature of disk protrusions and demonstrated
that so-called “chondromata” actually were intervertebral disk
herniations and not neoplastic lesions.
Veterinary reports of intervertebral disk herniation followed in
1881, when Janson a described an apparent disk herniation at the
fourth-to-fifth lumbar vertebrae in a young dachshund. Subsequent
reports by Pommer a in 1937 again considered the lesion to be either
proliferative tissue or a cartilaginous tumor originating from the
intervertebral disk. Investigations during the 1940s by several au-
thors 6,7 determined intervertebral disk degeneration and herniation to
be the cause of paralysis or paraplegia in the dog. Classical descrip-
tions by Hansen 8 separated the disease process between the
chondrodystrophoid and nonchondrodystrophoid dogs and provided a
classification of disk herniations as either type I or type II. Type I
herniations typically were of considerable size and were explosive,
causing trauma to the spinal cord and hemorrhage from the vertebral
sinuses. These herniations were confined to the chondrodystrophoid
breeds and could occur at any age. Type II herniations, on the other
hand, were smaller, with a more regular and often symmetrical pro-
file, and they were seen more commonly in nonchondrodystrophoid
dogs over eight years of age.
Following the preliminary work by Olsson, 9,10 Hoerlein,11,12 and
Funkquist, 13 the literature from the last two decades has focused on
the incidence, clinical signs, diagnosis, and treatment of the disease.

JOURNAL of the American Animal Hospital Association 55

56 JOURNAL of the American Animal Hospital Association
Figure 1—Scanning electron micrograph of the annulus fibrosus.
Individual lamellae can be seen distinctly. Note the alternating
direction of the collagen fibers in each lamellar layer.
As a result, management of intervertebral disk her-
niation by a combination of medical and surgical
methods is well established, with successful rehabili-
tation occurring in 71% to 100% of cases. 3,14–16
Investigations into the microscopic and ultrastruc-
tural properties of the intervertebral disk, its biome-
chanical function, and causes of degeneration have
been the basis of numerous reports in the medical
literature. An excellent review of the human interver-
tebral disk was provided by Humzah 17 in 1988. It is
hoped that this article will provide the reader with a
comprehensive and comparative summary of the cur-
rent knowledge regarding the canine intervertebral
disk. In Part I, the structure and function of the inter-
vertebral disk will be described, and in Part II, the
processes and possible causes of degeneration in both
chondrodystrophoid and nonchondrodystrophoid dogs
will be explained.
Normal Anatomy
An intervertebral disk exists between each pair of
vertebrae along almost the entire length of the spinal
column.18 Only the atlanto-axial joint does not have
an interposing intervertebral disk. Dorsally and ven-
trally, the intervertebral disk is bound by, and is in
places continuous with, the dorsal and ventral longi-
tudinal ligaments. Laterally, the smooth, fibrocarti-
laginous surface of the disk is visible when the
surrounding musculature is removed from the verte-
bral column. 18,19
Three distinct anatomical regions (i.e., the annulus
fibrosus, the nucleus pulposus, and the cartilaginous
end plates) are seen upon sectioning the disk in the
sagittal plane.18,19 Each distinctive portion imparts a
unique functional characteristic to the disk. Collec-
tively, a structure is created which is able to resist
and impart stability against deforming loads, yet still
January/February 1998, Vol. 34
permit flexibility of the spine when these loads are
within physiological limits.20–23
The Annulus Fibrosus
The annulus fibrosus is a fibrous basket that envelops
the nucleus pulposus. 19,24 In transverse section, it ap-
pears as concentric rings of fibrous tissue which com-
pletely encircle the nucleus pulposus. When
transected in the sagittal plane, these rings impart a
banded appearance to the annulus. Microscopically,
these bands are seen as layers of intricate fibrocarti-
laginous lamellae, each composed of numerous, par-
allel fibrous bundles [Figure 1].25 Each lamellar layer
arises from the cartilaginous end plate and surround-
ing vertebral body and runs a roughly parallel course
between adjacent vertebrae. The lamellae are quite
separate and distinct from one another, and no inter-
connection is visible at the optical microscopic
level.25 As will be discussed in a subsequent section,
the lamellae are able to glide over each other during
biomechanical loading. The directional arrangement
of the fibrous bundles alternates in sequential lamellae.24,25
The number and thickness of the lamellar layers in
the annulus fibrosus of the dog are unknown. In hu-
man lumbar disks, 15-to-38 distinct layers have been
reported.24,26–28 About half of these layers do not form
complete rings around the nucleus pulposus, an inci-
dence which increases with age. 24 It has been shown
that the lamellar layers are interrupted most frequently
at the dorsolateral aspect of the annulus fibrosus, and
it is suggested that the high level of lamellar disconti-
nuity may induce an inherent weakness at this point. 24
The annulus fibrosus is composed almost entirely
of fibrous tissue; indeed, 70% of its dry weight is
collagen.19,29,30 This fibrous tissue is produced and
maintained by the cellular elements which are located
between the fibrous bundles. These cells are long,
thin, and biconvex and are typical of fibrocytes found
in other tissues in the body. 8 Their main cellular prod-
uct is collagen, with type I collagen predominating in
the normal annulus fibrosus. 19,30 Small concentrations
of type III collagen have been isolated from the pe-
riphery of the annulus fibrosus. 31 Toward the inner
margins of the annulus, the cellular elements are more
numerous, and the nuclei of the cells become bigger
and slightly rounded in appearance.8 In these inner
regions, a gradual increase in the concentration of
type II collagen has been reported.19,30
Other structures in the annulus fibrosus are visible
only with the electron microscope and include elastic
fibers 28,32,33 and nerve endings.34–37 Johnson, et al., 33
described a three-dimensional, elastic fiber meshwork
in all regions of the human intervertebral disk. This
meshwork is developed better in regions of the annu-
lus which connect to adjacent vertebrae. Elastic fi-
bers are arranged circularly, longitudinally, and
January/February 1998, Vol. 34
obliquely within the lamellae of the annulus
fibrosus.32 Individual elastic fibers pass between the
lamellar layers, and they are believed to impart some
dynamic flexibility to the disk. 32,33 The presence of
similar structures in the canine intervertebral disk has
not been determined.
The peripheral third of the annulus fibrosus in the
human34,35,37 and dog36 is innervated by a number of
fine nerve endings. Dissection of the human lumbar
intervertebral disk 35 has revealed that the posterior
(i.e., dorsal) region of the annulus fibrosus is inner-
vated by branches from the sinuvertebral nerve (i.e.,
meningeal rami). A similar structure was not identi-
fied during the dissection of the canine thoracolum-
bar spine and, in contrast to the human disk, the
canine annulus fibrosus is innervated only sparsely.
The dorsal longitudinal ligament, however, is inner-
vated profusely. 35 No nerve endings have been de-
scribed in the inner regions of the annulus fibrosus or
nucleus pulposus of either the human or canine disk.
The Nucleus Pulposus
The nucleus pulposus is a remnant of the noto-
chord, 18,19 which was an early phylogenetic develop-
ment of the vertebral column. In the young animal,
the nucleus pulposus is a gelatinous globule, slightly
translucent in color. 8 When sectioned, the nucleus
pulposus will exude moisture persistently from its cut
surface. 18 The nucleus pulposus is bounded ventrally
and dorsally by the annulus fibrosus, but lies in close
contact with the cartilaginous end plates at its cranial
and caudal boundaries. 18 In the cervical and lumbar
regions especially, the nucleus pulposus is located
slightly eccentrically in the intervertebral disk so that
the ventral portion of the annulus fibrosus is two-to-
three times as wide as the dorsal portion. 18
The lamellae of the annulus fibrosus become pro-
gressively more disorganized at the transitional zone
between the two regions.8 The orderly lamellar ar-
rangement typical of the annulus eventually disinte-
grates into an irregular, three-dimensional lattice of
collagen fibers. Ground substance is present in much
greater quantity than in the annulus fibrosus, result-
ing in wide spaces between individual fibers.19,27
Water is the principal component of the nucleus
pulposus, making up 80% to 88% of its content in
early life. 8,15,16,19,20 It has been shown that a constant
flux of water occurs from the disk with constant load-
bearing, and a diurnal variation in disk width has
been demonstrated in human subjects. 38 The gravita-
tional influence on weight-bearing has been proven
by the observation of significant increases in height
by astronauts following periods of weightlessness on
space missions.39
Water is attracted to, and bound within, the disk by
the proteoglycan constituents of the ground sub-
Intervertebral Disk 57
stance. 20,29,40,41 The proteoglycans are very large,
complex molecules, and their role in the structural
differentiation and function of tissues is becoming
increasingly recognized. The proteoglycan molecule
appears to influence the function of the intervertebral
disk because of its considerable molecular size, the
very high negative charge it imparts to the matrix, its
degree of aggregation with hyaluronic acid, and its
association with the collagen elements of the nucleus
pulposus.
Each proteoglycan monomer consists of a single
protein backbone from which numerous polysaccha-
ride subunits, the glycosaminoglycans, arise.40,42–46
The glycosaminoglycans are themselves comprised
of long chains of two monosaccharides in an alternat-
ing sequence, the composition of which will vary
between tissues. In the intervertebral disk of all spe-
cies, the glycosaminoglycans of importance include
chondroitin-6-sulfate, keratan sulfate, and hyaluronic
acid. Chondroitin-6-sulfate is the larger molecule,
with a molecular weight (MW) of 2x10 4. Each disac-
charide unit carries a double negative charge. Keratan
sulfate has a MW of only 5 to 20x103 . It has a single
negative charge and is less numerous in the immature
nucleus pulposus. Keratan sulfate molecules usually
are concentrated about the proximal end of the pro-
tein backbone, resulting in a “keratan-rich” region;
chondroitin-6-sulfate molecules are scattered more
randomly. Due to the intense charge repulsion be-
tween the highly negatively charged glycosaminogly-
can side chains, the whole molecular arrangement of
the proteoglycan monomer assumes the characteris-
tics of a bottle-brush, with the side chains held rigidly
perpendicular to the backbone. The very high nega-
tive charge imparted to the matrix of the nucleus
pulposus also creates a significant osmotic gradient
which attracts and binds water molecules into the
wide spaces around the glycosaminoglycan molecules.
In certain instances, numerous proteoglycan mono-
mers will bind with hyaluronic acid, a process known
as aggregation.47–50 Binding sites appear very spe-
cific, with each proteoglycan monomer separated by
a distance of 20 nm. Binding of the two molecules is
stabilized by a small glycoprotein link. 51 The purpose
of aggregation is not understood clearly, but it is
believed that the production of such a large molecule
would help bind the proteoglycan subunits into the
matrix. A loss of aggregation would permit greater
dispersion of the proteoglycan monomers away from
the matrix, particularly during weight-bearing.
Normal aging of the nucleus pulposus is associated
with several changes in the quality and quantity of
proteoglycan monomers.52–54 In their investigation in
the greyhound, Ghosh, et al.,55 determined that by
five years of age in the dog, the predominant glycos-
aminoglycan molecule in the matrix of the nucleus
58 JOURNAL of the American Animal Hospital Association
Figure 2—In the nucleus pulposus, the proteoglycan monomers
appear to maintain a close affinity for type II collagen fibers, due
to convalent bonds which develop between the carbohydrate
moieties of each molecule. Since the highly negatively charged
proteoglycan molecules also bond strongly with water, this
affinity would appear to impart type II collagen with an enhanced
ability to withstand compressive loads.
pulposus has become keratan sulfate, with relative
concentrations of chondroitin-6-sulfate continuing to
fall for the rest of the dog’s life. Increased concentra-
tions of these new glycosaminoglycan molecules typi-
cally are localized about the cells, suggesting that the
changes are due to active cellular metabolism rather
than degeneration of existing molecules. The overall
concentration of proteoglycan within the nucleus
pulposus also falls from an immature level of 40% to
only 33% by eight years of age. In addition, a greater
proportion of the proteoglycan monomers are able to
be extracted from the matrix of the elderly disk, im-
plying a reduction in aggregation with age. As the
January/February 1998, Vol. 34
concentration of the glycoprotein-link molecule re-
mains unchanged over this period, this decreased ag-
gregating ability appears to be due to a loss of the
binding region on the proteoglycan monomer. The
observation of similar modifications to the
proteoglycan molecule in other connective tissue
structures of the body 56,57 suggests that they represent
a gradual maturation and development of the inherent
structures, perhaps in response to changes in the func-
tional requirements of the animal.
The nucleus pulposus contains considerably less
collagen than the annulus fibrosus. The gradual tran-
sition of collagen composition recorded in the annu-
lus fibrosus continues, 19 with type II collagen
predominating in the nucleus pulposus. 30 This transi-
tion would appear to have considerable biomechani-
cal significance. The molecular structure of type I
collagen provides exceptional resistance to tensile
loading,58 a quality exploited in skin, tendons, muscle,
and other tissues where this collagen type predomi-
nates. Type II collagen, by comparison, is found al-
most exclusively in load-bearing, cartilaginous tissues
throughout the body. 57 Type II collagen contains about
nine times more hydroxylysine amino acid residues
than any other type of collagen molecule. Since
hydroxylysine is known to interact readily with car-
bohydrate molecules, this difference is considered to
impart type II collagen with a high degree of associa-
tion with the glycosaminoglycan side chains of the
proteoglycan monomers 59 [Figure 2]. This intimate
association with the highly hydrophilic proteoglycan
molecule provides type II collagen with an enhanced
ability to resist compressive loads.
A variety of cell types (e.g., chondrocytes,
fibrocytes, and notochordal cells) have been described
in the nucleus pulposus. 8,60–62 Intermediate cell types
also have been described.61 In the young nucleus
pulposus, the predominant cell type is the chondro-
cyte. Unlike the cells in the annulus fibrosus, these
cells typically are rounded and may be arranged in
small “nests” with several other cells. Each nest is
separated by the fine collagen lattice. Fibrocytes occur
more frequently in the adult disk.8,61 This increased
incidence may represent a senile phenomenon. This sug-
gestion is given credence by the observation of many
intermediate forms of mesenchymal cells in the aging
intervertebral disk. These intermediate cells have fea-
tures common to both chondrocytic and fibrocytic cells.
In the very immature disk, notochordal cells may
persist as sole remnants of this phylogenetic vertebral
column. 62 Though uncommon, these cells may be
found in clusters within the nucleus pulposus of the
fetus, but such clusters decrease in frequency with
increasing age. The distinctive feature of the noto-
chordal cell is an abundance of glycogen found
densely packed within its cytoplasm. 62
January/February 1998, Vol. 34
Johnson, et al.,60 have reported an additional cell
type in the human intervertebral disk. The location of
this cell type appears to be confined to the matrix
abutting the junction of the nucleus pulposus and the
adjacent cartilaginous end plate. These spindle-shaped
cells resemble fibrocytes but are characterized by
unusually long cytoplasmic processes, which termi-
nate as bulbous swellings. It is suggested that these
long cytoplasmic processes allow the cell to maintain
the matrix of the central regions of the avascular
nucleus pulposus, while keeping the cell body close
to nutrients which diffuse through the cartilaginous
end plate.
With advancing age, the number of cells showing
signs of degeneration, characterized by pyknotic and
disintegrating nuclei, begins to increase.8,17 However,
despite this rise in the proportion of nonviable cells,
the absolute number of cells in the nucleus pulposus
appears to increase with age. This finding is sup-
ported by analysis of the deoxyribonucleic acid
(DNA) content of the human nucleus pulposus, which
increases progressively with age from 0.30 mg DNA/
gram at seven years to 0.61 mg DNA/gram by 42
years of age.17
The Cartilaginous End Plates
The cartilaginous end plates represent the cranial and
caudal boundaries of the intervertebral disk and are in
contact with the associated vertebral body. 18 In the
young animal, the surface of the cartilaginous end
plate is lined with a soft, translucent material which,
histologically, resembles hyaline cartilage. This car-
tilaginous surface is about 1-to-2 mm thick at the
periphery, but it thins toward the center where it may
become barely discernible. A slight concavity in the
central portion of each cartilaginous end plate coin-
cides with the area where the nucleus pulposus lies in
close contact with it.
The cartilaginous end plate is implicated frequently
in the nutrition of the intervertebral disk by diffusion
of nutrients across its surface. Previous investiga-
tions 63–68 have revealed that only the thin, central
portion of the cartilaginous end plate is permeable.
Vascular channels have been described in this portion
of the cartilaginous end plate, and these appear to be
in direct communication with the marrow spaces of
the vertebral body. 63 Large venous sinuses are seen
occasionally within the human vertebral body, adja-
cent to the osteochondral junction at the central por-
tion of the cartilaginous end plate. 17
Fibers from the annulus fibrosus and the nucleus
pulposus become interwoven with the collagen fibers
of the cartilaginous end plate and bony trabeculae to
form strong, stabilizing attachments called Sharpey’s
fibers. 24,25 This intimate weaving of fibrous elements
of connective tissue and bone is typical of most soft-
Intervertebral Disk 59
hard tissue attachments in the body. Fibers from the
more peripheral regions of the annulus fibrosus inter-
mingle with the fiber bundles of the dorsal and ven-
tral longitudinal ligaments and with the periosteal
fibers of the vertebral bodies.
Motion of Animals and The Role of the
Vertebral Column
Animal species with a high degree of locomotory
specialization are termed cursorial.69,70 The evolution
of the cursors from simple walkers was the result of
several selective advantages. Cursors are able to for-
age for food over a wide area, seeking new sources of
food or water when familiar sites fail or when sea-
sonal variations make a particular habitat unsuitable.
It is possible to segregate the evolutionary progress
of the herbivorous (i.e., prey) and the carnivorous
(i.e., predator) species. The requirements of their cho-
sen habitats placed great demands on the develop-
ment of their musculoskeletal system.
Cursorial herbivores may spend up to 16 hours a
day foraging for food, and their habitat may be vast.
Standing is the customary posture for these animals;
sitting, although possible, is an unusual activity. To
provide skeletal support with the minimum expendi-
ture of energy, the vertebral column is comparatively
rigid.71,72 This rigidity is promoted by well-devel-
oped ligamentous supports and increased skeletal ar-
ticulations. In the thoracic region, mobility is limited
chiefly by the large, dorsal spinous processes which
are required to provide mechanical struts for the in-
sertion of the nuchal ligament and epaxial muscles of
the head to offset the effect of the large, heavy head
present in these animals. 72 Flexibility in the caudal
thoracic and lumbar regions of the spine is limited
further due to broadening of the dorsal spinous pro-
cess, so that the interspace is minimal. 72 The interspi-
nous and supraspinous ligaments also are thickened
in this location. Lateral flexures of the spine are re-
stricted by the broad transverse processes. The great-
est movement in the equine vertebral column occurs
at the interspace of the first and second thoracic ver-
tebrae, which permits grazing activity, and at the
lumbosacral area.73
The position of the herbivores in the food chain
necessitates the need for rapid retreat from predators.
The vertebral column is comparatively inflexible;
therefore, development of speed in these animals has
been achieved by lengthening the stride through modi-
fications to the appendicular skeleton. 70 The effective
length of the limb has been increased by the animal
walking on the distal end of the third phalanx. In the
specialist runner, in particular, the skeletal complex-
ity of the distal limb is reduced, and all weight is
borne by a single digit; the remaining four digits
become redundant. 69,70 In other runners living in habi-
60 JOURNAL of the American Animal Hospital Association
Site of Lumbar Disc Degeneration in M
with data from Hansen HJ (19
50
45
Percent (%)
40
35
30
25
20
15
10
5 Gage ED (1975)
T12-13
L1-2
L5-S1
L2-3
L3-4
L4-5
Disc Space
Figure 3A
Figures 3A, 3B—(A) Proportion of disk herniation recorded at
each lumbar disk space in humans (with data from Hansen HJ8 );
(B) proportion of herniations recorded at each thoracolumbar
intervertebral disk space in the dog (with data from Gage ED 2
and Brown NO, et al. 3).
tats which are especially mountainous, muddy, or un-
even, development of the hoof shows some variation
to ensure a firm foot-fall in the rough terrain. 69 En-
durance is enhanced by the pendulum action of a
comparatively lengthened antebrachial region, the
motion of which is effected by a large muscle mass
about the shoulder and hips acting over a shortened
length. Comparatively small contractions of the limb
musculature create an increased stride length with a
resultant increase in speed.
In contrast with the herbivorous species, the devel-
opment of the musculoskeletal system in the predator
species was dictated by the need to obtain live food. 71
The “long chase, hot pursuit of the victim at close
quarters, prey-seeking in burrows, the catching of
live fish, specialisation for hunting small and large
animals, group or solitary hunting, and feeding on
carrion”71 all created special conditions dictating the
motion and limb morphology of the carnivore. The
need for manipulative functions by the distal limb
resulted in the retention of all digits and development
of a rotatory action in the forelimbs. The morphology
of this area is greatest in the cat because the claws are
used to seize and hold prey. 71 The dog, on the other
hand, is more likely to seize prey in its teeth.
A characteristic feature of the carnivore skeleton
is the flexibility of the spine 71,72 which is most obvi-
ous during stalking, in the pursuit of prey through
winding burrows, and in the final lunge and struggle
with the victim at the kill. The flexibility of the spine
also is advantageous during high-speed running, when
the considerable vertical mobility of the vertebral
column promotes an increase in the length of the
stride. This contributes to an acceleration in the speed
of running. 69
The active vertical mobility of the spine is re-
flected in the structural design of the vertebral col-
umn. The vertebral column of the dog is very flexible
January/February 1998, Vol. 34
Frequency of Disc Herniation at each Inters
250
No of cases
200
150
100
50
Brown NO et al (197
T11-12
0
T10-11
T13-L1
T12-13
L1-2
L2-3
L3-4
L4-5
L5-6
Intervertebral spa
Figure 3B
in the dorsal direction and fairly mobile in the ventral
direction. 72 This mobility is especially large in the
diaphragmatic region (i.e., thoracolumbar junction).
Pivoting of the vertebral column at the diaphragmatic
region provides a propulsive thrust to the hind limbs,
which are drawn under the body during the gallop. 69
The greater mobility of the vertebral column is asso-
ciated with a narrowing of the dorsal spinous pro-
cesses to increase the interspinous space, and with a
poorly developed supraspinous ligament. 72 A compli-
cated system of interspinous ligaments and muscles
has developed in their place. The epaxial musculature
also is quite fleshy and well developed. 72 The inter-
vertebral disk plays an important role in the attenua-
tion of the impacts passing through the vertebral
column during running, as well as in conferring the
spine with its distinguishing flexibility in these species.
The intervertebral disk in all animals must be able
to resist and attenuate a variety of biomechanical
forces. Interestingly, intervertebral disk disease is re-
corded most frequently at the most mobile region of
the vertebral column in all animals. For example,
degeneration of the intervertebral disk between the
first and second thoracic vertebrae and at the lum-
bosacral region is recorded in the horse, 74 and the
latter region also is affected commonly in the hu-
man 23 [Figure 3A]. However, clinical disease associ-
ated with disk degeneration is recorded infrequently
in the horse; 74 this is not surprising due to the relative
immobility of the vertebral column. Indeed, the more
typical complaint is associated with hyperextension
of the spine, due to riding and excessive jumping,
resulting in impingement of the dorsal spinous pro-
cesses and arthritic changes in the articular facets. 74
In the dog, degeneration of disks about the diaphrag-
matic region is more common, with 70% of all clini-
cal cases of disk herniation occurring between the
12th thoracic (T12 ) and second lumbar (L2 ) verte-
brae1–3,8 [Figure 3B].
Biomechanics of the Intervertebral Disk
To enable mobility of the vertebral column, the inter-
vertebral disk acts as a deformable tissue between the
January/February 1998, Vol. 34
Figure 4—When a compressive load is passed through the
normal intervertebral disk, a hydraulic pressure is generated
within the gelatinous nucleus pulposus. This is radiated in all
directions and is absorbed by the annulus fibrosus. The com-
pressive force is, in this way, converted into a predominantly
tensile force within the annular fibers which resists collapse of
the intervertebral disk space. The tensile force is largest in the
outer layers of the annulus fibrosus, and it is in this area that
most injuries are sustained (redrawn, with modification, from
White and Panjabi 23).
individual vertebral bodies. This role requires it to be
flexible enough to permit the extremes of movement
associated with locomotion, yet rigid enough to with-
stand the normal physiological forces acting along
the vertebral column. How the intervertebral disk tol-
erates these apparently conflicting qualities has been
the focus of considerable investigation. 75–91
When any structure is bent, the elements on the
concave side are compressed while those on the con-
vex side are under a state of tension. A gradual state
of transition between these two states exists, and at
one place within the beam the tensile and compres-
sive forces are balanced completely. This neutral zone
is referred to as the axis of movement.72,73 Investiga-
tions in the horse and human have shown that in the
cervical and lumbar regions of the vertebral column,
the axis of movement passes directly through the cen-
ter of the eccentrically located nucleus pulposus.73,92
In the thoracic region, the axis of movement (and
accordingly, the nucleus pulposus) is located more
centrally within the intervertebral disk, probably re-
flecting the influence of the rib cage on vertebral
column stability. 72
The majority of experiments on intervertebral disk
function have been performed on isolated but intact
disk units, bounded by thin sections of the adjacent
vertebral bodies.75,76,78–81,83,89,91 In most cases, the
neural arch and other associated soft-tissue elements
have been removed, enabling the investigators to fo-
cus solely on the activity of the intervertebral disk. In
these experiments, the intervertebral disk “unit” was
Intervertebral Disk 61
subjected to a variety of controlled, compressive-load-
ing forces. The applied load was classified as static
(i.e., a single, continuous load, often of increasing
intensity, with each loading event followed by a pe-
riod of recovery) or dynamic (i.e., repetitive loading
of many cycles per second). The intervertebral disk is
found to react quite differently to these loads, a qual-
ity which is quite typical of other elastic or semielastic
(i.e., viscoelastic) structures. 82
Under normal conditions, the intervertebral disk
can be subjected to five possible loading conditions:
axial compression, tension, bending, shear, and tor-
sion. 23 In most cases, a physiological biomechanical
force probably would be a combination of several, if
not all of these. For simplicity, let’s first consider
loading of the intervertebral disk along its neutral
axis. This results in the generation of a purely com-
pressive force acting through the center of the nucleus
pulposus. 23,78,89 The reaction of the disk to loading is
examined by measuring the amount of positional dis-
placement which occurs and changes in disk mor-
phology. Under a gradually increasing static load, the
intervertebral disk “unit” initially is quite flexible
and deforms easily. 75,78,81–83 As the load increases,
the disk becomes progressively stiffer, with a stable
state occurring after several minutes. The resultant
load-displacement curve is sigmoid in shape, a fea-
ture typical of all semielastic structures. 23 Slight
micromovement of the disk detectable under sustained
loading has been termed “creep” and is believed to be
associated with gradual efflux of fluid from the inter-
stices of the disk. 81 This flux of fluid is dependent
directly on the size of the load.
As the compressive load is applied across the in-
tervertebral disk, the force is absorbed mostly by the
gelatinous nucleus pulposus, resulting in the genera-
tion of a hydraulic pressure within the disk which is
radiated in all directions.20,23 As the nucleus pulposus
is squeezed, the annular fibers react by sliding over
each other to form a more tightly packed arrange-
ment, thereby restraining the disk circumference in
spite of a reduction in disk width. This action results
in the generation of large tensile stresses (estimated
to be about four-to-five times the applied compres-
sive load) within the lamellar fibers which makes the
annulus fibrosus very stiff, thereby preventing it from
collapsing under the weight of the compressive load
[Figure 4]. It has been shown that the annular lamel-
lae are three times stronger when loaded along the
direction of their fibers, 93 so it is presumed that the
alternating arrangement of the lamellae, together with
the obliquity of the lamellar fibers, enables them to
align themselves in the most efficient manner to coun-
teract the forces generated during loading.23,80,86
A number of studies have indicated that the nucleus
pulposus normally is kept under a constant degree of
62 JOURNAL of the American Animal Hospital Association January/February 1998, Vol. 34

compression by the surrounding musculature.85–88,94
This intradiskal pressure (or preload) has been mea-
sured in dogs86,88 and humans. 85,87 It is speculated
that the preload tension within the intervertebral disk
takes up the slack within the annular fibers and pro-
vides a cushion for resistance against tensile forces.
Bending, torsional, and shear loads are considered
to represent more closely the normal physiological
10. Olsson E. Observations concerning disk fenestration in dogs. Acta
Orthop Scand 1951;20:349–56.
11. Hoerlein BF. Intervertebral disk protrusions in the dog. Part II: symp-
tomatology and clinical diagnosis. Am J Vet Res 1953;14:270–4.
12. Hoerlein BF. Intervertebral disk protrusions in the dog. Part III: radio-
logical diagnosis. Am J Vet Res 1953;14:275–83.
13. Funkquist B. Decompressive laminectomy in thoracolumbar disk pro-
trusion with paraplegia in the dog. J Sm Anim Pract 1970;11:445–51.
14. Hoerlein BF. The status of the various intervertebral disk surgeries for
the dog in 1978. J Am Anim Hosp Assoc 1978;14:563–70.

activity of the disk than purely compressive loads. 15.
Indeed, experimental studies suggest that it is these 16.
loading conditions that are more likely to result in
traumatic disruption of the intervertebral disk.77 Re- 17.
sistance to these loads is aided by the activity of the
18.
other stabilizing elements of the vertebral column, 23
including the long and short ligaments of the spine 95 19.
and, in particular, the articular facets. 96,97 Moreover,
20.
in the live animal, physiological function of the disk
is aided by variations in thoracic and abdominal pres-
Hoerlein BF. Canine neurology. Diagnosis and treatment. 3rd ed. Phila-
delphia: WB Saunders, 1978:470–560.
Shores A. Intervertebral disk syndrome in the dog. Part 1: pathophysiol-
ogy and management. Comp Cont Ed Pract Vet 1981;3:639–47.
Humzah MD, Soames RW. Human intervertebral disk. Structure and
function. Anat Rec 1988;220:337–56.
Evans HE, Christensen GC. Miller’s anatomy of the dog. 2nd ed.
Philadelphia: WB Saunders, 1979:235–9.
Coventry MB. Anatomy of the intervertebral disk. Clin Orthop
1969;67:9–15.
Hendry NGC. The hydration of the nucleus pulposus and its relation
to intervertebral disk derangement. J Bone Joint Surg [Br]
1958;40:132–43.

sures, 84 which have been shown to influence dramati-
cally the biomechanical function of the vertebral
column and, in particular, the intervertebral disk. 88
A degenerating nucleus pulposus can have serious
consequences on the function of the intervertebral
disk and vertebral column. The changes that occur in
the intervertebral disk and particularly in the nucleus
pulposus are therefore the focus of the second article.
a
Cited in: Hoerlein BF, Canine neurology. Diagnosis and treatment. 3rd ed.
Philadelphia: WB Saunders, 1978:470–1.
Acknowledgments
The authors are grateful to Dr. Brian Goulden and
Professor Elwyn Firth for editorial assistance during
the preparation of this article. The excellent drawings
were prepared by John Fuller, and the authors are
indebted to his skill. The authors also would like to
thank Dr. Mike Targett for his assistance with the
scanning electron microscope.
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 Influence of Thoracic Conformation and
Genetics on the Risk of Gastric Dilatation-
Volvulus in Irish Setters
Body measurements, history of gastric dilatation-volvulus (GDV), and other data
were obtained for 155 Irish setters at the 1994 National Specialty Show. The dogs
ranged in age from 6.5 months to 12.4 years (mean±standard deviation [SD],
3.6±2.6 years); 11 (7%) of the dogs had histories of GDV. Gastric dilatation-volvulus
risk increased 33% for each year of age (p of 0.01). Dogs with the deepest thorax
relative to width (ratio range, 1.61 to 1.85) had a significantly greater GDV risk than
those with the shallowest thorax (ratio range, 1.20 to 1.50); the odds ratio was 8.45;
the 95% confidence limits were 1.44 to 49.57; and the p value equaled 0.02. Having
a relative (particularly a parent) with GDV also increased GDV risk. Five-generation
pedigrees yielded a significantly higher mean coefficient of relationship for the 11
dogs with GDV than for the 11 dogs without GDV. J Am Anim Hosp Assoc 1998;34:64–73.

Diana Schellenberg, MS Introduction

Qilong Yi, MD, PhD
Nita W. Glickman, MS, MPH
Lawrence T. Glickman, VMD, DrPH
O rence rates, GDV remains a serious, life-threatening disease.4–8
From the Department of Veterinary
Pathobiology (Schellenberg, Yi, L.T.
Glickman) and the
Center for Applied Ethology and Human-
Animal Interaction (N.W. Glickman),
School of Veterinary Medicine,
Purdue University,
West Lafayette, Indiana 47907-1243.
Doctor Schellenberg’s current address is
8200 Ruidoso Road NE,
Albuquerque, New Mexico 87109.
Doctor Yi’s current address is
165 St. George Street,
Toronto, Ontario, Canada M5R 2M2.
Gastric dilatation-volvulus (GDV; i.e., bloat) in dogs is an acute
condition characterized by malposition of the stomach, rapid accumu-
lation of air and gas in the stomach, increased intragastric pressure,
and cardiogenic shock.1 Standard treatment involves intensive therapy
for shock, gastric decompression, and surgical repositioning of the
stomach followed by intensive postoperative care. 2,3 Although refine-
ments in surgical techniques have reduced case-fatality and recur-
Many host and environmental factors have been implicated in the
etiopathogenesis of GDV. 7,9 One retrospective analysis of predispos-
ing factors for GDV risk among purebred dogs found that increasing
age and increasing body weight were important risk factors. The
overall pattern of risk for different breeds suggested that thoracic
conformation (i.e., a deeper and narrower chest) was an important
determinant of susceptibility.10 In a subsequent review of thoracic
radiographs from 437 dogs of 17 breeds, the mean thoracic depth/
width ratio alone accounted for 37% of the variability in GDV risk
among these breeds. 11 When GDV risk was evaluated as a function of
both thoracic depth/width ratio and the size of the breed (i.e., adult
body weight), 76% of the variability was explained.
The study described here was conducted to assess the relationship
between thoracic conformation and GDV risk for individual dogs and
to evaluate evidence for genetic determinants. The Irish setter was
selected for the study because previously it was shown to rank fifth
highest in GDV risk among 24 of the most popular dog breeds 10 and
because the authors have had good cooperation from Irish setter
owners.
Materials and Methods
In June 1994, at the Irish Setter Club of America (ISCA) National
Specialty Show in Canton, Ohio, dogs were enrolled in the study if

64 JOURNAL of the American Animal Hospital Association

January/February 1998, Vol. 34
Figure 1—Distribution of thoracic depth/width ratios for 155 Irish
setters measured at the National Specialty Show in 1994. Black
shading in bars indicates dogs with a history of gastric dilatation-
volvulus (GDV).
their owners volunteered to participate. Body mea-
surements were made, which included length and
height, depth and width of the thorax, and depth and
width of the abdomen using techniques described pre-
viously. 12 Each dog owner was asked to complete a
brief, written questionnaire [see Appendix on page
70] which included questions on the dog’s age and
history of GDV and the history of GDV for its full
siblings, parents, or grandparents. After the show, a
letter was mailed to participants requesting a pedi-
gree for the dog measured at the show, with annota-
tions as to the GDV history of its relatives. Additional
pedigrees for Irish setters were solicited through breed
club mailings.
The distributions of thoracic depth/width ratios in
the dogs with and without histories of GDV were
compared using a Kolmogorov-Smirnov test. 13 The
risk of GDV associated with the age, sex, thoracic
depth/width ratio, and bloat history of relatives was
assessed by calculating adjusted odds ratios (ORs),
Wald’s 95% confidence limits (95% CLs), and prob-
ability values. A p value of less than 0.05 was consid-
ered significant. All statistical analyses were done
using SAS computer software (SAS/STAT a ). The OR
is an approximation of relative risk, which in turn is
the incidence rate in a group exposed to a factor
divided by the incidence rate in a group not exposed
to the factor. An OR greater than 1 indicates a posi-
tive association between the factor and the disease;
the larger the OR, the stronger the association. Mul-
tiple logistic regression analysis was used to evaluate
the increase in GDV risk associated with potential
risk factors.
The dogs for which annotated, five-generation
pedigrees were obtained were designated as index
dogs. Wright’s equations 14 were used to calculate co-
efficients of inbreeding and relationship for index
dogs with and without histories of GDV. The coeffi-
cient of inbreeding is the probability that two genes
which an individual receives from its parents at a
Gastric Dilatation-Volvulus 65
randomly selected autosomal locus are identical by
descent. The coefficient of relationship is the prob-
ability that one gene selected at random from an indi-
vidual dog is identical to a gene selected at random
from a second dog (i.e., the extent to which two
animals received their genes from the same ances-
tors). For both coefficients, differences in the means
between dogs with and without histories of GDV were
evaluated using the Wilcoxon’s Score (rank sum)
test. 13
Results
Body measurements and GDV histories were obtained
at the Irish setter show for 155 dogs, of which 84
(54%) were females and 69 (45%) were males (sex
was not reported for two dogs). The mean
age±standard deviation (SD) was 3.6±2.6 years
(range, 6.5 months to 12.4 years). Eleven (7%) of the
dogs had histories of at least one episode of GDV.
These 11 dogs ranged in age from less than one year
to 12.4 years at the time of the show. Increased age
was associated with a significantly increased risk of
GDV; the OR of 1.33 in Table 1 implies that the risk
increased by 33% for each year of life. The age at
onset of the first episode was reported for 10 dogs
and ranged from 0.75 to 10.5 years (mean±SD,
4.1±3.44 years). The risk of GDV was higher for
females than for males, but this association was not
statistically significant.
The mean thoracic depth/width ratio±SD was
1.61±0.11 (range, 1.45 to 1.79) for the dogs with
histories of GDV and 1.54±0.13 (range, 1.23 to 1.85)
for those without histories of GDV. The distribution
of thoracic depth/width ratios [Figure 1] was not sig-
nificantly different (p of 0.16) between the two
groups. The risk of GDV did increase significantly,
however, with an increasing thoracic depth/width ra-
tio, even when adjusted for sex and age. When dogs
with the highest ratios were compared to those with
the lowest ratios, the risk of GDV was increased
significantly [Table 1]. None of the other body mea-
surements (body weight; length and height of the
dog; thoracic length, depth, and width; abdominal
depth and width; and abdominal depth/width ratio)
were associated significantly with the risk of GDV
(data not shown).
Gastric dilatation-volvulus risk was increased for
index dogs which had parents, sibling(s), or any fam-
ily member with a history of GDV, although the con-
fidence limits enclosed 1.0, and p values exceeded
0.05 [Table 2]. The relatively wide confidence limits
indicate that the estimates of the OR were unstable;
this may reflect the small size of the group with a
history of GDV.
Five-generation pedigrees with analyzable data on
bloat histories were obtained for 11 dogs with histo-
66 JOURNAL of the American Animal Hospital Association January/February 1998, Vol. 34

Table 1
Risk Factors for Gastric Dilatation-Volvulus (GDV) for 155 Irish Setters:
Multivariate Logistic Regression Analysis* of Thoracic Conformation, Sex, and Age

Risk Factor Odds Ratio 95% Confidence Limits p Value

Thoracic depth/width ratio
1.20–1.50† 1.00 — —
1.51–1.60 2.20 0.28–17.47 0.46
1.61–1.85 8.45 1.44–49.57 0.02
χ2 trend=3.97; p=0.05
Sex
Male† 1.00 — —
Female 2.98 0.69–12.83 0.14

Age (yrs) 1.33 1.07–1.65 0.01

* Log likelihood chi square (χ2)=14.39; p=0.007

†
Reference category

Table 2
History of Gastric Dilatation-Volvulus (GDV) in 155* Irish Setters
in Relation to a History of GDV in Their Relatives

History of GDV
History of GDV in Index Dog Odds 95% Confidence p
in Relatives Yes No Ratio Limits Value
GDV in any sibling No† 5 108 1.00 — —
Yes 2 11 3.93 0.68–22.67 0.15
GDV in either parent No† 6 108 1.00 — —
Yes 5 26 3.46 0.98–12.22 0.06
GDV in any grandparent No† 5 62 1.00 — —
Yes 1 30 0.41 0.05–3.70 0.66
GDV in any family member No† 3 45 1.00 — —
Yes 6 59 1.53 0.36–6.43 0.73

* Number of index dogs does not total 155 because of missing data
†
Reference category

ries of GDV and 11 dogs which never had GDV. Dogs
with histories of GDV had a higher mean coefficient
of inbreeding than the dogs with no history of GDV
[Table 3], but the difference was not statistically sig-
nificant. However, the mean coefficient of relation-
ship was significantly greater for dogs with histories
of GDV compared to those that never had GDV.
Discussion
Gastric dilatation-volvulus risk likely is influenced
by numerous predisposing characteristics of the dog
and by its environment and management. A previous
study identified age, body weight, and status as a
purebred as important risk factors for GDV.10 In pure-
bred dogs, compared with the reference category of
dogs 2.0 to 3.9 years old (OR of 1.0), the OR was 1.6
in dogs 4.0-to-6.9 years old, 2.7 in dogs 7.0-to-9.9
years old, and 4.9 in dogs more than 10 years old.
This implies that the risk for dogs 7.0-to-9.9 years old
is almost three times as high as that for dogs 2.0-to-
3.9 years old.
The median age at death was 7.5 years for 537
Irish setters in veterinary teaching hospitals from 1980
through 1989 in a study of comparative longevity. 15
January/February 1998, Vol. 34
Table 3
Coefficients of Inbreeding and Relationship for Irish Setters
Based on Five-Generation Pedigrees
History of Gastric Dilatation- No. of
Volvulus in Index Dog Dogs
Coefficient of Inbreeding
Yes 11
No 11
Coefficient of Relationship
Yes 11
No 11
*SD=standard deviation
In a 1992 ISCA Health Committee survey, 16 356
breeders and owners completed questionnaires regard-
ing their attitudes and opinions about the health of the
breed. The average life span of Irish setters they had
owned was 11.1 years, but this did not include dogs
that died of accidental causes or disease at a young
age. That survey was not designed to estimate GDV
prevalence, but the average age at bloat onset was
noted to be 5.8 years. The Irish setters enrolled in the
Bloat Inheritance and Morphometry Study at the 1994
show were relatively young (mean age, 3.6 years).
More of these dogs can be expected to develop GDV
in the future. Their health status will be followed at
least through February 1998 as part of a prospective
study of risk factors for GDV.
A radiographic study confirmed veterinarians’
clinical impressions that deep-chested breeds are more
likely to develop GDV, and the relationship between
breed risk of GDV and average thoracic conformation
(depth/width ratio) was quantified. 11 The Irish setter
had the largest average thoracic depth/width ratio
among 17 breeds included in the radiographic study.
The results of the retrospective study of Irish setters
measured at the National Specialty Show in 1994
[Figure 1, Table 1] imply that the pattern of GDV risk
among breeds also holds for individual dogs within a
breed (i.e., a greater thoracic depth/width ratio is
associated with greater risk of GDV). This hypothesis
currently is being tested in a prospective study in
Irish setters and 10 other breeds; more than 1,900
dogs have been enrolled in this study.
Identification of risk factors which predispose dogs
to GDV would allow practitioners to advise their cli-
ents regarding selection of breeding stock and the
possibility of prophylactic treatment. Studies are
needed to determine how well measurements of the
thoracic depth/width ratio in very young dogs can
predict risk of GDV later in life.
Gastric Dilatation-Volvulus 67
Mean Coefficient
±SD* p Value
0.120±0.113
0.092±0.082 0.431
0.115±0.157
0.044±0.084 0.004
Anecdotal evidence exists of a familial predisposi-
tion to GDV within breeds, 9 but to the authors’ knowl-
edge, no simple inheritance pattern is apparent.
Ascertaining complete GDV histories of litters over a
decade is difficult even for breeders who attempt to
follow the fate of puppies sold from their kennels.
Irish setter owners who participated in the study at
the National Specialty Show in 1994 were asked about
the GDV history of the relatives of each measured
dog [Table 2]. The OR of 3.93 for GDV risk for dogs
that had “any sibling” with a history of GDV implies
an influence of shared genetic or early environmental
factors or both. The OR of 3.46 for GDV risk for dogs
that had a parent with a history of GDV suggests a
genetic influence. However, a larger study is needed
to determine whether these influences are statistically
significant in this breed. The ongoing prospective
study, which includes evaluation of family history of
GDV as a risk factor, should provide additional evidence
on this point in Irish setters and the other 10 breeds.
Coefficients of inbreeding and relationship have
been used to evaluate genetic influence in a number
of canine diseases. A study of four-generation pedi-
grees of 21 St. Bernards with osteosarcoma and 18
controls showed that the index dogs were related to
each other more closely than were the controls (mean
coefficients of relationship±SD, 0.055± 0.04 and
0.02±0.01, respectively). 17 The significant difference
(p less than 0.001) indicated that there was familial
clustering of osteosarcoma within the breed. In con-
trast, the index dogs actually were less inbred than
the controls (mean coefficients of inbreeding±SD,
0.21±0.03 and 0.04±0.06, respectively), although the
difference was not significant (p greater than 0.05).
These findings suggested that inbreeding itself does
not increase susceptibility to osteosarcoma, but that
one or more genes predisposing to the disease are
transmitted in certain family lines.
68 JOURNAL of the American Animal Hospital Association
Both the coefficient of relationship and the coef-
ficient of inbreeding were significantly higher in
seven Dandie Dinmont terriers with pituitary-depen-
dent hyperadrenocorticism than in a representative
sample of the breed population in the Netherlands. 18
These results suggested that a genetic factor is in-
volved in the pathogenesis of this disease.
Significantly increased coefficients of inbreeding
were found in five of seven diseases studied in
Bouviers Belge des Flandres in the Netherlands. 19
Dogs with osteochrondrosis dissecans, food allergy,
autoimmune disease, neoplasms, or hypoplastic tra-
chea were inbred more highly than controls, while
those with flea allergy or laryngeal paralysis were
not. A cross-sectional study of Dutch pedigree data
for this breed20 showed that dogs with dysphagia-
associated muscular dystrophy were descended from
one closely related group of ancestors. The inbreed-
ing level for this “high-risk ancestor” group was sig-
nificantly higher for the affected dogs than controls,
but the homozygosity due to all other ancestry was
equal for the affected dogs and controls. Another
study showed that Kooiker (Dutch Decoy) dogs with
necrotizing myelopathy had higher coefficients of in-
breeding than the rest of the breed population. 21
Lingaas and Klemetsdal found no effect of inbreed-
ing on hip dysplasia in their population study of
golden retrievers in Norway.22
In the study reported here, annotated five-genera-
tion pedigrees were available for 22 Irish setters: 11
with a history of GDV and 11 with no history of
GDV. The mean coefficient of inbreeding was higher,
but not significantly so, for the dogs with a history of
GDV [Table 3]. Thus, this data does not provide
convincing evidence that inbreeding itself exerts a
strong influence on the risk of GDV in Irish setters.
The mean coefficient of relationship was significantly
higher for the 11 Irish setters with histories of GDV
[Table 3] (i.e., these dogs were related more closely
to each other than were the 11 dogs with no history of
GDV). It may be that specific genes within certain
lines are responsible for the increased risk of GDV in
this breed through their determination of thoracic con-
formation (i.e., the depth/width ratio). A study has
been conducted in one high-risk family of Irish set-
ters, and the findings are consistent with this hypoth-
esis. 23 Additional family studies are needed in which
thoracic conformation can be evaluated for patterns
of inheritance and for its relationship to the risk of
GDV.
The results of the study reported here are consis-
tent with a role for inheritance in the risk of GDV.
However, the genetic influence does not appear to
follow a simple pattern and may or may not be limited
to the phenotype of the thoracic depth/width ratio. A
possible genetic contribution to this disease in other
January/February 1998, Vol. 34
breeds has not yet been defined. Generalizations about
the relationship between body measurements and
GDV risk of individual dogs within a breed must
await analysis of the data from the authors’ ongoing
prospective study.
While the data from Irish setters is not yet suf-
ficient for specific genetic counseling, it suggests
that a practitioner who treats an Irish setter with GDV
would be justified in alerting the owner to the possi-
bility of increased risk of GDV in that dog’s siblings
or offspring.
A case-control study in pet dogs evaluated other
predisposing risk factors such as temperament and
modifiable factors such as diet and frequency of feed-
ing. 24 Results of such epidemiological studies will
provide veterinarians and dog owners with the infor-
mation necessary to make informed decisions regard-
ing prevention and treatment of GDV.
a
SAS Institute, Inc., Cary, NC
Acknowledgments
This study was supported by the Morris Animal Foun-
dation and donations from the Irish Setter Club of
America (ISCA) and individual dog owners. The au-
thors express their appreciation to Mrs. Connie
Vanacore, Chairman, ISCA Health Committee; all
the Irish setter owners who participated in the study;
Tim Emerick for technical assistance; and Dr. Robert
H. Schaible for helpful discussions.
References
1. Burrows CF. Acute gastric dilatation. Calif Vet 1983;6:11–3.
2. Lantz GC. Treatment of gastric dilatation-volvulus. In: Bojrab MJ,
Birchard SJ, Tomlinson JL, Jr, eds. Current techniques in small animal
surgery. Philadelphia: Lea & Febiger, 1990:224–31.
3. Brockman D. Management of gastric dilatation-volvulus syndrome in
the dog. In Practice 1994;16:63–6, 68–9.
4. Brockman D, Washabau R, Drobatz K. Canine gastric dilatation-volvu-
lus syndrome in a veterinary critical care unit: 295 cases (1986–1992).
J Am Vet Med Assoc 1995;207:460–4.
5. Brourman JD, Schertel ER, Allen DA, Birchard SJ, DeHoff WD. Factors
associated with perioperative mortality in dogs with surgically managed
gastric dilatation-volvulus: 137 cases (1988–1993). J Am Vet Med
Assoc 1996;208:1855–8.
6. Van Sluijs FJ. Maagdilaatatie-volvulus bij de hond: huidige opvattingen
en retrospectief onderzoek bij 160 patienten [Gastric dilatation-volvulus
in the dog: current views and a retrospective study in 160 patients].
Tijdschr Diergeneeskd 1991;116:112–21.
7. Hosgood G. Gastric dilatation-volvulus in dogs. J Am Vet Med Assoc
1994;204:1742–7.
8. 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.
9. Burrows CF, Ignaszewski LA. Canine gastric dilatation-volvulus. J Sm
Anim Pract 1990;31:495–501.
10. Glickman LT, Glickman NW, Perez CM, Schellenberg DB, Lantz GC.
Analysis of risk factors for gastric dilatation and dilatation-volvulus in
dogs. J Am Vet Med Assoc 1994;204:1465–71.
11. Glickman LT, Emerick T, Glickman NW, et al. Radiological assessment
of the relationship between thoracic conformation and the risk of gastric
dilatation-volvulus in dogs. Vet Radiol Ultrasound 1996;37:174–80.
January/February 1998, Vol. 34
12. Glickman LT, Glickman NW, Schellenberg D, et al. Epidemiologic
studies of bloat in dogs. Vet PreViews 1995;2:10–3, 15.
13. Fleiss JL. The design and analysis of clinical experiments. New York:
John Wiley & Sons, 1986:74–8.
14. Wright S. Coefficients of inbreeding and relationship. Am Nature
1922;56:330–9.
15. Patronek GJ, Waters DJ, Glickman LT. Comparative longevity in dogs
and humans: implications for gerontology research. J Gerontol Biol Sci
1997;52:171–8.
16. Dodds WJ. Estimating disease prevalence with health surveys and
genetic screening. Adv Vet Sci Comp Med 1995;39:29–96.
17. Bech-Nielsen S, Haskins ME, Reif JS, Brodey RS, Patterson DF, Spielman
R. Frequency of osteosarcoma among first-degree relatives of St. Ber-
nard dogs. J Natl Cancer Inst 1978;60:349–53.
18. Scholten-Sloof BE, Knol BW, Rijnberk A, Mol JA, Middleton DJ,
Ubbink GJ. Pituitary-dependent hyperadrenocorticism in a family of
Dandie Dinmont terriers. J Endocrinol 1992;135:535–42.
Gastric Dilatation-Volvulus 69
19. Ubbink GJ, Knol BW, Bouw J. The relationship between homozygosity
and the occurrence of specific diseases in bouvier Belge des Flandres
dogs in The Netherlands. Vet Quart 1992;14:137–40.
20. Peeters ME, Ubbink GJ. Dysphagia-associated muscular dystrophy: a
familial trait in the bouvier des Flandres. Vet Rec 1994;134:444–8.
21. Mandigers PJJ, Van Nes JJ, Knol BW, Ubbink GJ, Gruys E. Hereditary
necrotising myelopathy in Kooiker dogs. Res Vet Sci 1993;54:118–23.
22. Lingaas F, Klemetsdal G. Breeding values and genetic trend for hip
dysplasia in the Norwegian golden retriever population. J Anim Breed
Genet 1990;107:437–43.
23. Schaible RH, Ziech J, Glickman NW, Schellenberg D, Yi Q, Glickman
LT. Predisposition to gastric dilatation-volvulus in relation to genetics
of thoracic conformation in Irish setters. J Am Anim Hosp Assoc
1997;33:379–83.
24. Glickman L, Glickman NW, Schellenberg DB, Simpson K, Lantz GC.
Multiple risk factors for the gastric dilatation-volvulus syndrome in
dogs: a practitioner/owner case-control study. J Am Anim Hosp Assoc
1997;33:197–204.
70 JOURNAL of the American Animal Hospital Association January/February 1998, Vol. 34

Appendix
CANINE GASTRIC DILATATION-VOLVULUS PROGRAM
SCHOOL OF VETERINARY MEDICINE
Purdue University West Lafayette IN 47907-1243
Phone: (317) 494-6301 FAX: (317) 494-9830
____________________________________________________

BLOAT INHERITANCE PATTERNS AND MORPHOMETRY IN PUREBRED DOGS

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
✰ ✰ IRISH SETTER CLUB OF AMERICA NATIONAL SPECIALTY ✰ ✰
Canton Ohio, June 1994
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Background Information

Purdue University, with support from the Morris Animal Foundation and individual do-
nors, is studying risk factors for bloat in dogs (canine gastric dilatation-volvulus; CGDV).
Preliminary data on risks in different breeds have raised the possibility that a dog’s confor-
mation is a factor.
The Irish Setter has been selected for this epidemiologic study because it is considered
a high-risk breed. This breed ranked 5th highest among 24 breeds compared in our recent
study (L.T. Glickman et al., Journal of the American Veterinary Medical Association,
104:1465-1471, May 1, 1994).

Study Description

The purposes of this study are to:

1. Determine breed and age norms for body measurements of Irish Setters.

2. Relate body measurements to a history of bloat in the dogs measured and in

their relatives.

3. Relate the bloat history and body measurements to the risk of bloat in the future.

Data from the dogs in this study will be analyzed and compared with data from other
studies of risk factors for bloat. Data identifying individual dogs and owners will be held
strictly CONFIDENTIAL. We are seeking help from breeders because breeders are
uniquely qualified to furnish certain types of information.

If you are willing to help —

• take a few minutes to furnish the information on page 2, and

• allow your dog to be measured (see page 3).

If you prefer not to provide your name and address or the dog’s bloat history, you can
still participate by allowing your dog to be measured and providing the dog’s call name (to
avoid any duplications), sex, and birth date or age.

ALL INFORMATION IDENTIFYING INDIVIDUAL DOGS IS CONFIDENTIAL!

Please turn the page

January/February 1998, Vol. 34 Gastric Dilatation-Volvulus 71

Appendix (cont’d)
CONFIDENTIAL Information To Be Supplied by Owner
✎ (Please print)
A. Dog’s Descriptive Information (must be completed)

1. Dog’s call name __________________ 2. Sex: Male____ Female ____

[=0] [=1]
3. Birth date _____/_____/_____ or Age ______years
Month Day Year

B. Owner Information
(Mr.)
(Mrs.)
1. Name (Ms) ___________________________ 2. Telephone (____)___________
First M.I. Last Area

3. Address ____________________________________________________
Street Apt.

____________________________________________________
City State Zip
C. History of Bloat (Please check one)
1. Has this dog ever had an episode of bloat? No____ Yes____ Don’t know____
[=0] [=1] [=2]
If yes, when? _____/_____/____
Month Day Year

2. Did either of this dog’s parents ever have bloat? No____ Yes____ Don’t know____
[=0] [=1] [=2]
If yes, which parent? Sire _____ Dam ____
[=0] [=1]

3. Did any of this dog’s full brothers or sisters ever No____ Yes____ Don’t know____
have bloat? [=0] [=1] [=2]

4. Did any of this dog’s grandparents ever have bloat? No___Yes___ Don’t know____
[=0] [=1] [=2]
D. Permission to Contact
1. I am willing to be contacted by the CGDV Research Team in the future to provide
CONFIDENTIAL information about whether or not my dog has an episode of bloat. I
would also be willing to provide other information about the dog, such as diet, feed-
ing frequency, etc. My address and phone number are listed above.

Signature_______________________________ Date__________

2. I would be willing to provide a pedigree for this No____ Yes____

dog if needed in the future. [=0] [=1]

E. Comments
72 JOURNAL of the American Animal Hospital Association January/February 1998, Vol. 34

Appendix (cont’d)
Illustration of Body Measurements

It is important to determine if there is a relationship between various body measure-

ments and dogs’ susceptibility to bloat. Your cooperation is needed to determine body
weight, length, height, chest length, chest depth, chest width, abdominal depth, and
abdominal width.

Measurements with Tape Measure To Be Made by Purdue Staff

Length of Dog Height from Top of Back to Floor Length of Chest

Measurements with Canine Caliper To Be Made by Purdue Staff

Depth of Chest Depth of Abdomen

Width of Chest Width of Abdomen

January/February 1998, Vol. 34 Gastric Dilatation-Volvulus 73

Appendix (cont’d)
CONFIDENTIAL

Instructions and Coding Form for Measurements Made by Purdue Staff

Weight (ask the owner):

Specify actual or estimated body weight to the nearest 1/2 lb. ___________lb
[0] Actual ____ or [1] Estimated ____
Body Condition (check one):
Thin: Pronounced underweight, no obvious body fat. [1] Thin ____
Lean: Little body fat evident, skeletal structure obvious. [2] Lean ____
Optimum: Moderate body fat, rib cage easily palpable but not too obvious. [3] Optimum __
Overweight: Rib cage not visible when dog moves, bones of chest [4] Overweight ____
barely palpable, bodyweight noticeably more than normal.
Obese: Unable to feel ribs, large amounts of subcutaneous fat can be [5] Obese ____
grasped by hand; obvious incapacity due to excess fat.

Body Measurements

All measurements should be made with the dog standing on a level surface. Measure-
ments with the tape measure or Canine Caliper should be made to the nearest 1/2 inch.

Length of Dog: Use tape measure to determine length Length of Dog________in

from the humeral deltoid tuberosity to the ischium. (Keep
tape measure straight — do not bend around dog.)

Height from Top of Back to Floor: Use tape measure to Height from Floor________in
determine the distance from the scapular border perpen-
dicular to the floor, just behind the elbow.

Length of Chest: Use tape measure to determine the Length of Chest________in

distance along the length of the sternum from the manu-
brium to the costal arch (base of xiphoid).

Depth of Chest: Use Canine Caliper held perpendicular Depth of Chest________in

to the spine to determine the depth of the chest at the level
of the costal arch (base of xiphoid).

Width of Chest: Use Canine Caliper to determine the Width of Chest________in

width of the chest at the level of the costal arch.

Depth of Abdomen: Use Canine Caliper held perpen- Depth of Abdomen________in

dicular to the spine to determine the depth of the
abdomen at the level of the umbilicus.

Width of Abdomen: Use Canine Caliper to determine Width of Abdomen________in

the width of the abdomen at the level of the umbilicus.

Measurements made by: Date:

_____________________________________________ __________________
 Physaloptera Infection in 18 Dogs with
Intermittent Vomiting
Physaloptera infections were diagnosed endoscopically in 18 dogs. Each case
had vomiting as the primary clinical sign, and four cases had regurgitation as a
concurrent sign. Fecal flotations, using magnesium sulfate solution, were performed
in 12 of the 18 cases and were negative for Physaloptera eggs. In 12 of the 18
cases, only one worm was seen during endoscopic examination. Fifteen of 18 cases
were treated with pyrantel pamoate, and 10 of 12 cases with follow-up had resolution
of their vomiting. J Am Anim Hosp Assoc 1998;34:74–8.

Sharon K. Theisen, DVM, Introduction

Diplomate ACVIM
Suzanne N. LeGrange, DVM,
MS, Diplomate ACVIM
Susan E. Johnson, DVM, MS,
Diplomate ACVIM
Robert G. Sherding, DVM,
Diplomate ACVIM
Michael D. Willard, DVM, MS,
Diplomate ACVIM
RS
From the Department of Veterinary
Clinical Science (Theisen, Johnson,
Sherding),
College of Veterinary Medicine,
The Ohio State University,
601 Vernon L. Tharp Street,
Columbus, Ohio 43210 and the
Department of Veterinary Clinical Science
(LeGrange, Willard),
College of Veterinary Medicine,
Texas A&M University,
College Station, Texas 77843.
Doctor Theisen’s current address is
The Central Texas Veterinary
Specialty Hospital,
4544 South Lamar #760,
Austin, Texas 78745.
Doctor LeGrange’s current address is
the Veterinary Medical and Surgical
Specialty Practice,
1500 Elizabeth Avenue,
Charlotte, North Carolina 28204.
Nematodes of the genus Physaloptera inhabit the stomach and proxi-
mal duodenum of many carnivores. 1 In dogs and cats, infection with
Physaloptera spp. is caused most commonly by Physaloptera rara
and is characterized by intermittent vomiting. 2–4 Physaloptera spp.
produce embryonated eggs [Figure 1] that are passed in the feces and
may remain viable for up to 40 days in the environment. 4 These eggs
are ingested by an intermediate host (e.g., cockroach, cricket, beetle)4
where they hatch and become infective larvae.4 This intermediate
host may be ingested by a transport host (e.g., rodent, snake). 4 The
life cycle is completed when a dog or cat ingests an intermediate or
transport host. 4 The nematodes attach to gastric and duodenal mucosa
where they may cause small erosions, mild-to-severe inflammation,
and increased mucus production. 5 The worm burden often is low, with
an infected animal typically harboring only one-to-five nematodes.5
Diagnosis of Physaloptera spp. is difficult. Routine fecal flotation
may not yield eggs due to the small number of parasites, low fecun-
dity of the female nematodes, and the presence of a single sex infec-
tion. Additionally, the nematodes may cause clinical signs before
they mature and begin shedding eggs. 5 Detection of Physaloptera
spp. eggs requires fecal flotation using either sodium dichromate
solution (specific gravity of 1.36) or magnesium sulfate solution
(specific gravity of 1.20).6 Even with the optimum fecal flotation
solutions, eggs may not be detected.5 In the few reports available, the
clinical diagnosis of Physaloptera spp. infection has been made by
endoscopic detection of the adult worm(s). 2,3,7 This report describes
18 dogs that had signs of intermittent vomiting and had Physaloptera
spp. infection diagnosed endoscopically.
Materials and Methods
The clinical records of 18 dogs from Ohio and Texas with Physa-
loptera spp. infection, diagnosed using a flexible endoscope, were
reviewed retrospectively. Ten cases were evaluated at The Ohio State
University Veterinary Medical Teaching Hospital, and eight cases
were evaluated at the Texas A&M University Veterinary Medical
Teaching Hospital during the years 1983 through 1994. For each case,
the signalment, clinical signs, duration of illness, number of worms
detected, fecal flotation results, associated findings, and outcomes
were recorded [see Table].

74 JOURNAL of the American Animal Hospital Association

January/February 1998, Vol. 34
Figure 1—Egg of Physaloptera spp. recovered on a fecal flota-
tion from a dog. Note that the egg is thick walled and contains
a first-stage larva. These eggs typically measure 49 to 58 by 30
to 34 µ. (From: Hendrix C. Diagnostic Veterinary Parasitology.
2nd ed. St. Louis: Mosby, 1998; in press.)
Results
The 18 dogs ranged in age from eight months to 12
years (median age, three years). Vomiting was the
primary clinical sign in all cases. In addition, regurgi-
tation was a clinical sign in four cases. The duration
of clinical signs ranged from five days to 10 months
(median, 3.5 weeks), with 10 (56%) of 18 cases hav-
ing signs for less than four weeks.
Infection with Physaloptera spp. appears to be an
uncommon cause of vomiting in dogs. During the
time of this study, 441 gastroduodenoscopies were
performed at The Ohio State University Veterinary
Medical Teaching Hospital and Physaloptera spp.
were diagnosed in only 10 dogs. During the same
time, 530 gastroduodenoscopies were performed at
the Texas A&M University Veterinary Medical
Teaching Hospital, and eight dogs were diagnosed
with Physaloptera spp. infection.
Adult nematodes of the genus Physaloptera were
identified in all 18 cases upon endoscopic examina-
tion. Adult Physaloptera spp. worms are white, ap-
proximately 1 cm in length, and lie in an S-shaped
configuration or a straight line [Figure 2]. Nematodes
were found both attached to the mucosa and free on the
mucosal surface. The number of nematodes observed
endoscopically in each case varied from one to eight.
Only one nematode was seen in 12 (67%) of 18 cases.
Upon endoscopic evaluation, the gastric mucosa
appeared normal in eight cases. Endoscopic abnor-
malities in the remaining cases were generally mild
and consisted of slight thickening of the rugal folds
and pin-point hemorrhagic areas at the site of the
worm attachment to the mucosa. All observed nema-
todes were removed using grasping forceps through
the operating channel of the flexible endoscope. En-
doscopic biopsies of the gastric mucosa were
obtained in all cases. Nine of 18 cases had histopatho-
Physaloptera 75
Figure 2—An endoscopic view of a Physaloptera spp. nematode
on the gastric mucosa of a dog.
logical abnormalities characterized as mild-to-moderate
lymphocytic-plasmacytic gastritis. Peripheral eosino-
philia was present in only two cases. Fecal flotation
using magnesium sulfate solution was performed on
the feces from 12 cases; however, Physaloptera spp.
eggs were not identified in any of these samples.
In addition to the physical removal of all worms
detected, various nematocides were used to treat any
adult Physaloptera spp. that may have been over-
looked. Fifteen (83%) of 18 dogs received pyrantel
pamoate (15 mg/kg body weight, per os [PO] initially
and repeated in two-to-three weeks). Follow-up re-
sponses to therapy were obtained for 12 of these dogs.
Vomiting resolved in 10 (83%) of 12 pyrantel pamoate-
treated dogs. One dog treated with pyrantel pamoate
that had complete resolution of signs also received
cimetidine (10 mg/kg body weight, PO tid). Ivermectin
(200 µg/kg body weight, PO once) was used in two
(11%) of 18 cases and complete resolution of clinical
signs was seen in one case. The other case that received
ivermectin continued to vomit until metoclopramide
(0.4 mg/kg body weight, PO tid) was administered.
Fenbendazole (50 mg/kg body weight, PO once a day
for three days) was administered to one case and
there was a complete resolution of clinical signs.
Discussion
Identification of nematode eggs by fecal flotation
apparently is less reliable than endoscopic examina-
tion for diagnosis of Physaloptera spp. infections in
dogs. Detection of eggs may be unreliable for diagno-
sis of Physaloptera spp., because infections typically
involve fewer than 10 adult nematodes, 5 female nema-
todes produce a small number of eggs, or a single sex
infection may be present. Furthermore, the nematodes
 Table 76

Physaloptera Infection in 18 Dogs

Age Weight Signs/ Number of Fecal Associated

Breed (yrs) Sex* (kg) State Duration Worms Flotation Findings Treatment Outcome
Mixed-breed dog 12 MC 4.5 Ohio Vomiting and 1 Negative Peripheral Pyrantel pamoate; Lost to follow-up
regurgitation/8 wks eosinophilia metoclopramide
Poodle 1 M 2.7 Ohio Vomiting/40 wks 1 Negative None Pyrantel pamoate Complete resolution
Miniature 3 M 4.5 Ohio Vomiting and 4 Negative Delayed gastric Pyrantel pamoate Continued to vomit
schnauzer regurgitation/8 wks emptying
Labrador retriever 2 M 39.5 Ohio Vomiting and 1 Negative Plasmacytic Pyrantel pamoate Complete resolution
regurgitation/3 wks gastritis
Manchester terrier 3 FS 5.5 Ohio Vomiting/3 wks 1 Negative Lymphocytic- Pyrantel pamoate; Complete resolution
plasmacytic metoclopramide
gastritis
Mixed-breed dog 6 FS 6.4 Ohio Vomiting/12 wks 1 NP† Lymphocytic- Pyrantel pamoate; Complete resolution
plasmacytic cimetidine
gastritis
JOURNAL of the American Animal Hospital Association

Pointer 7 FS 25 Ohio Vomiting and 2 Negative Lymphocytic- Pyrantel pamoate; Complete resolution
regurgitation/4 wks plasmacytic metoclopramide
gastritis
Miniature 4 F 4.5 Ohio Vomiting/12 wks 2 Negative Delayed gastric Pyrantel pamoate Continued to vomit
schnauzer emptying
Rottweiler 4 MC 38.6 Ohio Vomiting/16 wks 1 Negative Lymphocytic- Pyrantel pamoate Complete resolution
plasmacytic
gastritis
Staffordshire bull 0.7 M 15.9 Ohio Vomiting/8 wks 1 Negative Lymphocytic- Pyrantel pamoate Complete resolution
terrier plasmacytic
gastritis
Miniature 2 F 6.4 Texas Vomiting/2 wks 1 NP None Pyrantel pamoate Complete resolution
schnauzer
Poodle 2 MC 6.4 Texas Vomiting/1 wk 8 Negative Peripheral Pyrantel pamoate; Complete resolution
eosinophilia ivermectin
Bassett hound 2 M 16.8 Texas Vomiting/3 wks 1 Negative None Ivermectin Resolved after 6
wks
Miniature 8 FS 8.6 Texas Vomiting/3 wks 5 NP None Pyrantel pamoate; Lost to follow-up
schnauzer ivermectin
January/February 1998, Vol. 34
 January/February 1998, Vol. 34

Table (cont’d)
Physaloptera Infection in 18 Dogs

Age Weight Signs/ Number of Fecal Associated

Breed (yrs) Sex* (kg) State Duration Worms Flotation Findings Treatment Outcome
Dachshund 4 FS 9 Texas Vomiting/3 wks 1 NP Lymphocytic- Fenbendazole Complete resolution
plasmacytic
gastritis
Mixed-breed dog 1 MC 35.9 Texas Vomiting/8 wks 1 NP Lymphocytic Pyrantel pamoate Lost to follow-up
gastritis
Dachshund 10 MC 19.5 Texas Vomiting/1 wk 5 NP Lymphocytic Ivermectin; Complete resolution
gastritis metoclopramide
Mixed-breed dog 1 FS 15.9 Texas Vomiting/2 wks 1 Negative None Pyrantel pamoate Complete resolution

* MC=castrated male; M=male; FS=spayed female; F=female

†
NP=not performed
Physaloptera
77
78 JOURNAL of the American Animal Hospital Association
can cause clinical signs before they mature and shed
eggs, and special solutions are required for flotation
of the eggs. 5 Three of the cases in this report had
undergone exploratory gastrotomies for diagnosis of
vomiting prior to presentation to the authors, and the
presence of Physaloptera spp. was overlooked in each
of these cases. Apparently, Physaloptera spp. are
overlooked easily during exploratory gastrotomy be-
cause of the low number of nematodes and their small
size (1-to-2 cm).
Detection of adult Physaloptera spp. endoscopi-
cally requires careful examination of the entire gas-
tric mucosa and proximal duodenum. The presence of
mucus, food, barium, or other material on the gastric
mucosa may obscure adult parasites. Nematodes of-
ten are hidden underneath rugal folds and are ob-
served best when the stomach is distended fully.
Worms attached to the pyloric mucosa may be over-
looked easily because of difficulty viewing this area
endoscopically. In one case, the duodenum was reen-
tered five times during one endoscopic procedure before
a parasite was detected. The use of the videoendo-
scope, which provides greater magnification of the
surface mucosa than a fiberoptic endoscope, also may
improve detection of nematodes. In one case, several
immature parasites were detected with a videoendo-
scope. These parasites had been overlooked previ-
ously during fiberoptic examination.
Isolated case reports of Physaloptera infections
that caused vomiting in dogs and cats have been pub-
lished previously. 2,3,7 All dogs in this report had vom-
iting as the presenting complaint. The mechanism for
the vomiting in dogs and cats with Physaloptera in-
fections is not understood fully. It may be secondary
to gastritis or duodenitis caused by the migration and
attachment of the worm to the mucosa.5 Eight (44%)
of the cases in this report had histological evidence of
gastritis. No correlation was found between the num-
ber of worms detected and the severity of the clinical
signs or the degree of inflammation seen on histologi-
cal examination of the biopsy samples.
Four (22%) cases were regurgitating as well as
vomiting. The regurgitation was presumed to be sec-
ondary to esophagitis induced by the vomiting.
Chronic vomition can lead to incompetence of the
gastroesophageal sphincter and promote reflux of gas-
tric acid and enzymes into the esophagus.8 Two of the
cases with concurrent regurgitation had slight
erythema of the distal esophagus and were diagnosed
with mild esophagitis. The other two cases each had a
normal-appearing esophagus but were noted to have a
wide open gastroesophageal sphincter during endos-
copy, which may have predisposed them to gastro-
esophageal reflux. Two cases also had evidence of
delayed gastric emptying based on the presence of
undigested food in their stomachs at the time of endos-
January/February 1998, Vol. 34
copy, despite 12-to-16 hours of fasting. Delayed gas-
tric emptying may occur in animals with chronic gas-
tritis, possibly because inflammatory lesions alter the
normal gastric electrical-mechanical activity which
may lead to gastric stasis. 9 Both of these cases had
been vomiting for two-to-three months.
If an infection with Physaloptera spp. is diagnosed
endoscopically, any observed nematodes should be
removed. Follow-up therapy with pyrantel pamoate,
to treat for any remaining worms (which is repeated
in two-to-three weeks) appears to be effective.
Ivermectin and fenbendazole were not administered
to enough cases to judge their efficacy. One cannot
exclude the possibility that the endoscopic removal
of all obvious parasites, rather than the administra-
tion of an anthelminthic, was the cause of clinical
improvement. Since none of the cases had positive
fecal flotations for Physaloptera spp., resolution of
the vomiting was used to evaluate the success of
treatment. Resolution of vomiting may not be an ac-
curate indicator of treatment results, because cases
that did not respond may have had other underlying
causes for their chronic vomiting. If infection with
Physaloptera spp. is suspected, a fecal flotation using
sodium dichromate solution or magnesium sulfate
should be performed; however, a negative test does
not eliminate the possibility of infection. Evaluation
of the vomitus for the presence of the Physaloptera
spp. eggs may be another option, since identification
of the eggs in the feces is difficult. Further investiga-
tion of this technique would be required to establish
its efficacy in diagnosing Physaloptera spp. infec-
tions. With increased awareness of Physaloptera spp.
infections as a cause of vomiting and chronic gastri-
tis, empiric treatment with anthelminthics such as
pyrantel pamoate may be warranted in dogs with
chronic vomiting prior to performing endoscopy.
References
1. Georgi JR. Parasitology for veterinarians. Philadelphia: WB Saunders,
1985:128.
2. Burrows CF. Infection with the stomach worm Physaloptera as a cause
of chronic vomiting in the dog. J Am Anim Hosp Assoc 1983;19:947–50.
3. Santen DR, Chastain CB, Schmidt DA. Efficacy of pyrantel pamoate
against Physaloptera in a cat. J Am Anim Hosp Assoc 1993;29:53–5.
4. Levine ND. Spirurorids. In: Levine ND, ed. Nematode parasites of domestic
animals and man. Minneapolis: Burgess Publishing, 1980:313–43.
5. Anderson NW. Disorders of the small intestine. In: Ettinger SJ, ed. A
textbook of veterinary internal medicine. Philadelphia: WB Saunders,
1975:1179.
6. Ehrenford FA. Diagnosis of Physaloptera in dogs by stool examination.
J Parasitol 1954;40(section 2):16.
7. Clark JA. Physaloptera stomach worms associated with chronic vomition
in a dog in Western Canada. Can Vet J 1990;31:840.
8. Jones BD, Jergens AE, Guilford WG. Diseases of the esophagus. In:
Ettinger SJ, ed. A textbook of veterinary internal medicine. Philadel-
phia: WB Saunders, 1989:1267–8.
9. Twedt DC, Magne ML. Diseases of the stomach. In: SJ Ettinger, ed. A
textbook of veterinary internal medicine. Philadelphia: WB Saunders,
1989:1313.
 The Fluctuation of Tear Production
in the Dog
The fluctuation and variation in canine tear production were established by
evaluating the results of daily Schirmer tear test I (STT I) and weekly STT I and
Schirmer tear test II (STT II) conducted on healthy dogs. The objectives of the study
were to determine the fluctuation in STT values in dogs and its significance on both
a daily and weekly basis; to determine the magnitude of the measured differences;
and to identify any factors that might influence the fluctuation in STT values or
variations of normal values between different dogs. The results of the study indicate
that fluctuations in the STT values occur on both a daily and weekly basis. The
fluctuations were only biologically significant on a week-to-week basis. There are
significant differences between STT I and STT II values in dogs. The results also
indicate that weight has a significant effect on STT values, with higher values
measured in dogs of increasing body weight. J Am Anim Hosp Assoc 1998;34:79–83.

Sheri L. Berger, DVM Introduction

Vickie L. King, MS, PhD
O of the patient. The Schirmer tear test II (STT II), which is performed
The Schirmer tear test (STT) is used to estimate tear production in
animals routinely; two methods have been developed. The Schirmer
tear test I (STT I) is the conventional method used by most veterinar-
ians. 1 The STT I evaluates both the basal and the reflex tearing ability
after the instillation of a topical anesthetic, solely evaluates basal tear
production. 1 Normal values for the STT I and STT II in dogs have
been established as 19.8±5.3 mm per minute and 11.6±6.1 mm per
minute, respectively. 1,2
To the authors’ knowledge, detailed analyses of the daily and
weekly fluctuations in STT values have not been described previ-
ously in the veterinary literature. The purposes of the study were to
assess the fluctuation in STT values in healthy dogs; to determine
whether there are significant daily or weekly fluctuations in STT
values; to identify any factors that could explain the fluctuation in
STT values; and to compare differences between STT I and STT II
values in dogs.

Materials and Methods

From the Departments of Small Animal
Clinical Sciences (Berger) and
Clinical and Population Sciences (King),
College of Veterinary Medicine,
University of Minnesota,
St. Paul, Minnesota 55108.
Doctor Berger’s current address is the
Department of Medicine,
The Animal Medical Center,
510 East 62nd Street,
New York, New York 10021.
Four healthy greyhounds with normal ophthalmic examination find-
ings were chosen from the hospital’s resident blood donor group. The
four dogs included one intact male, one neutered male, and two
spayed females. The age range was two to three years, and the weight
range was 25.4 to 32.4 kg. The STT I was performed once daily for
four consecutive days.
Twenty-six dogs representing many breeds were chosen from a
group of animals volunteered for the study by veterinary students and
hospital staff. The dogs were healthy, had normal ocular surface and
adnexal findings, and were not on medications other than heartworm
preventative. The 26 dogs included both sexes (four intact males,
nine neutered males, one intact female, and 12 spayed females); the
age range was 13 weeks to 12.5 years; and the weight range was 7.3 to

JOURNAL of the American Animal Hospital Association 79

80 JOURNAL of the American Animal Hospital Association January/February 1998, Vol. 34

Table 1
Results of Schirmer Tear Test I (STT I) Performed Once Daily for
Four Consecutive Days in Four Greyhounds

STT I (mm/min)
Age Weight Day 1 Day 2 Day 3 Day 4
(yrs) Sex* (kg) OD† OS‡ OD OS OD OS OD OS
2 M 27.7 15 15 20 23 17 17 22 21
3 FS 25.5 15 17 23 18 23 19 27 23
3 FS 25.4 21 18 22 19 23 21 19 19
3 MC 32.4 20 17 15 16 19 13 21 13

* M=male; FS=spayed female; MC=castrated male

†
OD=right eye
‡
OS=left eye

45.5 kg (mean weight, 24.4 kg). The STT I was per-
formed in these dogs once weekly for four consecu-
tive weeks.
Twenty-two dogs representing many breeds were
chosen (from the same population of volunteered
dogs) for inclusion in the second phase of the study.
The 22 dogs included both sexes (one intact male,
nine neutered males, 12 spayed females); the age
range was nine months to 12.5 years; and the weight
range was 7.3 to 40.9 kg. The STT II was performed
in these dogs once weekly for four consecutive weeks.
Seventeen of the 22 dogs that had the STT II test
performed also had the STT I performed once weekly
for four consecutive weeks before the STT II test was
performed.
Standard Schirmer tear test strips,a all of the same
lot number, were used throughout the study. 3 The
testing was conducted at the same time period, usu-
ally late morning or early afternoon, in an undis-
turbed examination area. 4 Tests always were
performed on the right eye first, followed by the left
eye. The test strips were placed in the inferior con-
junctival fornix, approximately two-thirds the dis-
tance from the medial to lateral canthus, for 60
seconds.5 In dogs that had STT II performed, one
drop of proparacaine hydrochloride (HCl)b was placed
on the ocular surface bilaterally, and this was re-
peated in 30 seconds. After one minute, the tears
were wicked from the inferior conjunctival fornix of
the right eye with a cellulose sponge,c and the STT
was performed. The tears then were wicked from
the left eye, and testing was conducted in a similar
fashion.
The daily STT I values were analyzed by repeated
measures analysis of variance (ANOVA). 6 The model
included a covariate of weight; effects of sex, eye,
and day; and interactions of sex by eye, day by weight,
day by sex, day by eye, and day by eye by sex. Mean
comparisons were performed by Fisher’s protected
least significant difference. The weekly STT I and
STT II values also were analyzed by repeated mea-
sures ANOVA. The model included covariates of
weight and age; effects of sex, eye, test, and week;
and the interactions of eye by test, weight by test, age
by test, week by weight, week by age, week by sex,
week by eye, week by test, week by eye by test, week
by weight by test, and week by age by test. All analy-
ses were performed by SAS.7 A p value less than 0.05
was considered significant.
Results
The daily STT I measurements in the four greyhounds
were collected only for four consecutive days [Table
1], because three of the dogs seemingly began to
anticipate the placement of the tear strip into the
conjunctival fornix. These dogs demonstrated ble-
pharospasm and began to lacrimate excessively when
approached for testing after the second day. On days
one, three, and four, there were no significant differ-
ences in the values obtained. On day two, weight,
sex, and the sex by eye interaction had a significant
effect on STT values. After adjusting for weight, the
females had higher STT values for the right eye
(mean, 19.53 mm per min) than the left eye (mean,
15.53 mm per min), but the males did not have sig-
nificantly different measurements between eyes (right
eye mean, 20.47 mm per min; left eye mean, 22.47
mm per min). Also, after adjusting for weight, the
males had higher values than the females for the left
eye but not for the right eye. Although there were
fluctuations in STT values, which ranged from de-
creases of 4 mm to increases of 12 mm from baseline
(day one), no significant changes were measured in
daily tear production over the four days of testing.
 Table 2
Results* of Schirmer Tear Test I (STT I) and Schirmer Tear Test II (STT II) in Dogs

STT I (mm/min) STT II (mm/min)

Weight Week 1 Week 2 Week 3 Week 4 Week 1 Week 2 Week 3 Week 4
Breed Age Sex† (kg) OD‡ OS§ OD OS OD OS OD OS OD OS OD OS OD OS OD OS
Golden 13 wks M 11.1 22 18 17 18 19 25 20 20 – – – – – – – –
January/February 1998, Vol. 34

retriever
Golden 4.5 yrs MC 32.3 20 20 27 27 13 18 17 23 – – – – – – – –
retriever
Labrador 7 yrs FS 22.7 14 13 17 13 12 18 7 15 – – – – – – – –
retriever
Terrier mix 6 yrs MC 14.8 19 23 17 22 21 23 18 19 – – – – – – – –
Viszla 7.5 mos M 18.6 17 15 22 18 14 13 25 24 – – – – – – – –
Boxer 4 mos M 14.5 27 19 22 21 24 24 22 20 – – – – – – – –
German 5 yrs MC 45.5 18 16 20 22 23 26 20 24 – – – – – – – –
shepherd
dog
Labrador 3 yrs F 28.2 17 18 17 18 22 20 16 18 – – – – – – – –
retriever
Greyhound 3 yrs FS 25.4 21 18 23 21 22 18 – – – – – – – – – –
Labrador- 6 yrs MC 30.9 22 18 20 18 23 27 17 19 17 13 17 14 – – – –
golden
retriever
mix
Labrador 4 yrs FS 25 17 18 18 18 30 30 29 27 16 7 11 9 3 5 10 3
retriever
Doberman- 6 yrs MC 38.6 19 17 23 19 23 27 23 22 18 17 18 16 17 18 20 18
Labrador
retriever
mix
Australian 8 yrs MC 19.1 21 16 17 17 23 26 17 29 17 10 11 5 7 2 13 5
cattle dog
Shetland 10 yrs FS 11.4 16 14 8 12 22 21 21 23 7 8 4 1 8 5 13 10
sheepdog
Greyhound 7 yrs MC 40.9 16 17 17 15 17 24 18 16 16 14 17 15 8 12 13 14
Chesapeake 9 mos FS 29.5 13 13 13 15 18 20 12 16 8 12 14 3 11 15 7 4
Tear Production

Bay-
Labrador
retriever
mix
81

(Continued on next page)

 Table 2 (cont’d) 82

Results* of Schirmer Tear Test I (STT I) and Schirmer Tear Test II (STT II) in Dogs

STT I (mm/min) STT II (mm/min)

Weight Week 1 Week 2 Week 3 Week 4 Week 1 Week 2 Week 3 Week 4
Breed Age Sex† (kg) OD‡ OS§ OD OS OD OS OD OS OD OS OD OS OD OS OD OS
Doberman 4 yrs FS 23.6 26 21 17 17 18 20 21 24 17 15 9 3 12 8 14 5
mix
Labrador 1.5 yrs FS 17.3 23 19 22 20 27 30 30 20 12 15 10 7 8 10 16 11
retriever
mix
Border 4 yrs FS 15.9 17 18 20 17 22 28 20 26 13 12 11 7 14 10 12 5
collie
Labrador 3 yrs FS 18.2 18 24 21 18 24 22 21 16 4 2 7 6 8 3 14 6
retriever
mix
Miniature 12.5 yrs MC 7.3 14 16 17 10 17 19 17 12 17 15 11 12 14 10 13 9
schnauzer
JOURNAL of the American Animal Hospital Association

Labrador 11 mos MC 18.2 17 14 24 22 16 17 15 15 4 7 0 12 4 16 8 13

retriever
mix
Collie- 2 yrs FS 18.2 18 21 17 13 19 21 18 17 15 9 15 2 10 3 4 12
shepherd
mix
Alaskan 4 yrs FS 32.1 14 19 18 17 30 24 23 18 20 22 21 25 18 20 22 17
malamute
Greyhound 2 yrs M 27.7 15 15 23 22 21 21 22 20 17 11 16 14 7 8 4 11
Greyhound 3 yrs FS 25.5 15 17 28 17 23 18 19 20 11 13 14 15 9 12 3 3
Shepherd- 1 yr MC 23.2 – – – – – – – – 8 9 8 5 9 9 11 11
Samoyed
mix
Siberian 6 yrs MC 22.7 – – – – – – – – 12 14 7 11 7 11 10 14
husky
Labrador 4 yrs MC 22.7 – – – – – – – – 16 22 14 17 16 15 19 18
retriever
mix
Doberman 3.5 yrs FS 36.4 – – – – – – – – 16 17 16 15 12 15 15 13
mix
Labrador 10 yrs FS 30.5 – – – – – – – – 22 19 12 14 17 12 14 10
retriever
January/February 1998, Vol. 34

* Results of STT I performed in 26 dogs and STT II in 22 dogs once weekly for four consecutive weeks (17 of the 22 dogs had both tests performed)
†
M=male; MC=castrated male; FS=spayed female; F=female
‡
OD=right eye
§
OS=left eye
January/February 1998, Vol. 34
In the 26 dogs that had the STT I performed weekly
for four consecutive weeks, significant differences in
STT I values were found (after adjusting for weight
and age) between weeks one and three, weeks two
and three, weeks one and four, and weeks three and
four [Table 2]. No significant differences in values
were found between weeks one and two and weeks
two and four. The data showed that for every 0.45-kg
increase in body weight, an 0.02 increase in STT I
values was measured. No significant differences were
found between the values obtained for the right and
left eyes or between the sexes.
In the 22 dogs that had the STT II performed
weekly for four consecutive weeks [Table 2], signifi-
cant differences in STT II values were found (after
adjusting for weight and age) between weeks one and
two, weeks one and three, and weeks one and four,
but not between weeks two and three, two and four,
and three and four. For every 0.45-kg increase in
body weight, an 0.12 increase in STT II values was
measured. In the 17 dogs that had both tests per-
formed, after controlling for weight, age, and sex,
there were significant differences between the STT I
and STT II values measured for all weeks.
Discussion
Clinical estimation of tear production is performed
by the Schirmer tear test. The test can be conducted to
estimate both basal and reflex tearing abilities (STT
I) or only basal tear secretion (STT II).1 The conven-
tional clinical test used is the STT I. Previously re-
ported normal values for the STT I in dogs are
19.8±5.3 mm per minute and 19.65±3.8 mm per
minute. 1,2,5 The STT II measures only basal tear pro-
duction, because reflex tearing is abolished by the
instillation of topical anesthetic. 1 The previously re-
ported normal value for the STT II in dogs is 11.6±6.1
mm per minute. 1
This study was conducted to assess the variability
over time (daily or weekly) of STT values in clini-
cally normal dogs. The authors concluded that STT I
and STT II values in dogs do fluctuate both daily and
weekly. Significant biological fluctuations were seen
week-to-week but not daily. Significant differences
were found in both STT I and STT II values between
dogs of different body weight (i.e., significantly
higher STT values were measured in dogs with higher
body weights). The differences in the STT values
reflecting basal tear production between dogs of dif-
ferent body weight were striking. Large dogs have
higher basal tear production when compared with dogs
of lesser body weight. These differences, although
still significant, decreased six-fold when reflex tear-
ing abilities were considered. This data suggests,
therefore, that smaller dogs have greater reflex tear-
ing abilities compared with larger dogs. Although
Tear Production 83
immune-mediated lacrimal adenitis has been impli-
cated as a significant cause of keratoconjunctivitis
sicca (KCS), it may not be coincidental that KCS is a
condition that typically affects small dogs since they
have inherently lower basal tear production when
compared to large dogs. The reason for the lower
basal tear production is not clear. As has been re-
ported previously, statistically significant differences
were found between the STT I and STT II values in
clinically normal dogs. 1
A previous study conducted by one of the authors
(Berger) reported the adverse effects of Tribrissen on
tear production in dogs.8 Results indicated a poten-
tially deleterious effect on tear production in dogs
taking Tribrissen, with dogs weighing less than 12 kg
at high risk for developing KCS. The data further
suggested that for every 10-kg decrease in body
weight, dogs taking the drug had a 2.5-times greater
risk for developing KCS. One of the limitations of
that study was a lack of a control population for
assessing the weekly fluctuation and variation of tear
production in clinically normal dogs. Although not
statistically significant, some dogs in that study ap-
peared to sustain decreases in their STT values while
on the drug. Results of the present study suggest that
those dogs were having typical fluctuations in weekly
tear production and not necessarily adverse reactions
to the drug.
a
Schirmer Tear Test strips; IOLAB Pharmaceuticals, Claremont, CA
b
0.5% Ophthaine solution; Apothecon, Princeton, NJ
c
Weck-Cel surgical spears; Xomed Surgical Products, Jacksonville, FL
References
1. Gelatt KN, Peiffer RL, Erickson JL, Gum GG. Evaluation of tear
formation in the dog, using a modification of the Schirmer tear test.
J Am Vet Med Assoc 1975;166:368–70.
2. Rubin LF, Lynch RK, Stockman WS. Clinical estimation of lacrimal
function in dogs. J Am Vet Med Assoc 1965;147:946–7.
3. Hawkins EC, Murphy CJ. Inconsistencies in the absorptive capacities of
Schirmer tear test strips. J Am Vet Med Assoc 1986;188:511–3.
4. Smith EM, Buyukmihci NC, Farver TB. Effect of topical pilocarpine
treatment on tear production in dogs. J Am Vet Med Assoc
1994;205:1286–9.
5. Harker DB. A modified Schirmer tear test technique. Vet Rec
1970;86:196–9.
6. Winer BJ. Statistical principles in experimental design. 2nd ed. New
York: McGraw Hill, 1971:514–39.
7. SAS user’s guide: statistic, version 5 edition. Cary, NC: SAS Institute,
Inc., 1985:549–640.
8. Berger SL, Scagliotti RH, Lund EM. A quantitative study of the effects
of Tribrissen on canine tear production. J Am Anim Hosp Assoc
1995;31:236–41.
 The Use of Propofol as an Induction
Agent for Halothane and Isoflurane
Anesthesia in Dogs
Cardiovascular, pulmonary, and quantitative electroencephalographic parameters
were assessed in 12 anesthetized dogs to determine the compatibility of the
injectable anesthetic propofol with halothane and isoflurane. No cases of apnea
were observed during induction of anesthesia. An adequate level of anesthesia was
established in each protocol as judged by both the lack of response to mechanical
noxious stimuli (i.e., tail clamping) and evidence of reduction in total amplitude of
brain wave activity. The initial propofol-mediated decrease in arterial blood pressure
continued during either halothane (52.4%) or isoflurane (38%) anesthesia without a
simultaneous increase in heart rate. The results of this study suggest that propofol,
in combination with inhalant agents, can be used effectively and safely for canine
anesthesia in veterinary practice. J Am Anim Hosp Assoc 1998;34:84–91.

Antonello Bufalari, DVM Introduction

Susan M. Miller, DVM
Claudia Giannoni, PhD
Charles E. Short, DVM, PhD,
Diplomate ACVA,
Diplomate ECVA
O characterized by rapid onset; short duration; rapid metabolism; lack
From the Section of Anesthesiology,
Department of Clinical Sciences,
College of Veterinary Medicine,
Cornell University,
Ithaca, New York 14853.
Propofol a is an intravenous anesthetic agent chemically unrelated to
barbiturates or other anesthetic agents. Propofol is a member of the
alkyl phenol family. It is available as a white, ready-to-use, oil-in-
water emulsion containing 10% soya bean oil, 2.25% glycerol, 1.2%
purified egg phosphatide, and 1% propofol sealed in 20-ml ampules.
It has a neutral pH, is isotonic, and because of its formulation it is
effective only when administered by intravenous injection. It does
not contain a preservative. Propofol has been used in premedicated
and nonpremedicated dogs and cats. 1,2 Propofol anesthesia in dogs is
of cumulation on repeated administration; some respiratory depres-
sion; and rapid, smooth recovery from anesthesia. 3,4
After many years, halothane b is still a frequently used inhalant
anesthetic in veterinary medicine. Halothane is a safe and effective
anesthetic when used properly, providing adequate anesthesia for
diagnostic and surgical procedures without excess depression of car-
diopulmonary and neurological functions.
Isoflurane c is a newer inhalant anesthetic with desirable pharmaco-
logic and clinical properties. Its use is well established in veterinary
medicine. Isoflurane has many positive characteristics such as low
biodegradability, fast onset of action, and rapid recovery because of
its relatively low blood solubility. As with all inhalant anesthetics,
isoflurane depresses cardiovascular, pulmonary, and neuronal func-
tions in a dose-dependent manner.5 Compared to halothane, isoflurane
is significantly less arrhythmogenic in dogs and cats.6
Since little clinical information exists on the use of propofol with-
out premedication for anesthetic induction followed by maintenance
with inhalants, this study was designed to compare the properties of
halothane and isoflurane as anesthetic agents after propofol induction
in the dog. Secondly, the authors intended to determine subjective
and objective guidelines for the effective and safe use of propofol/

84 JOURNAL of the American Animal Hospital Association

January/February 1998, Vol. 34
inhalant combinations at the lowest alveolar concen-
tration of halothane or isoflurane that would prevent
purposeful movement or brain wave activity changes
in response to noxious stimuli (i.e., tail clamping) in
a clinical environment.
Materials and Methods
The protocol was approved by the University Animal
Use Committee and conducted utilizing Good Labo-
ratory Practice (GLP) guidelines. Twelve (six females
and six males), purpose-bred, mongrel dogs were
used. Since the dogs had no health problems increas-
ing anesthetic risk, their physical status was classi-
fied as ASA 1 (American Society of Anesthesiologists
Classification Guidelines). Ages of the dogs ranged
from 15 to 20 months, and the average weight was
21.9 kg (range, 15.7 to 27.5 kg). The animals were
kept in kennels of appropriate size, fed a commercial
diet with continuous access to water, and received
routine health care. Food, but not water, was withheld
for at least six hours prior to induction of anesthesia.
Metabolic and hematological profiles were deter-
mined 24 hours prior to anesthesia.
Animals were divided randomly into two groups
and assigned to the experimental protocol. Each group
consisted of six dogs with equal distribution of fe-
males and males to nullify any gender influence on
the statistical studies. Group H received the induction
dose (6.6 mg/kg body weight) of propofol intrave-
nously (IV) over 60 seconds, followed by mainte-
nance of anesthesia with halothane. Group I received
the same propofol induction dose followed by main-
tenance of anesthesia with isoflurane. Immediately
after each anesthetic induction, intubation was com-
pleted and the endotracheal tube was connected to a
small-animal, semiclosed-circle system d with an oxy-
gen (O 2) flow of 2 L per minute. The dogs in both
groups breathed only O2 without inhalant anesthetic
until the two-minute, postpropofol induction data was
recorded; this allowed evaluation of the cardiopulmo-
nary and neurological effects of propofol as an induc-
tion agent. Then, either halothane or isoflurane was
delivered in O 2 using agent-specific, calibrated, out-
of-circle vaporizers. Initial vaporizer settings were
2.0% halothane and 2.5% isoflurane. Spontaneous
ventilation was maintained in all dogs. Anesthesia
was maintained with either halothane or isoflurane
for 30 minutes to determine responses to the transi-
tion from propofol to inhalant anesthesia. It has been
established that complete recovery from propofol (6.6
mg/kg body weight) anesthesia occurs within 30 min-
utes. 7 All dogs were evaluated for neurological and
cardiopulmonary responses during the maintenance
of anesthesia. Respiratory rates, end-tidal carbon di-
oxide (ET CO2 ) tension, and expired anesthetic gas
concentrations were measured at the connection of
Propofol 85
the endotracheal tube and the circle rebreathing
circuit. e The O 2 saturation (SpO2 ) was recorded with
the pulse oximeter probe placed over the margin of
the tongue. e The electrocardiogram f (EKG) was moni-
tored continuously during anesthesia. Heart rate and
blood pressures (i.e., systolic, diastolic, and mean)
were determined using a noninvasive system g with
a cuff placed on the front leg over the metacarpal
artery.
Rectal temperature was monitored throughout the
trial with no attempt to maintain preanesthetic values.
Preliminary data for all measurements (except ETCO 2,
SpO 2, and the electroencephalogram [EEG]) was col-
lected before induction with propofol. In addition to
the preanesthetic measurements, recordings were
made at two and five minutes after induction (the end
of the bolus dose of propofol) and at five-minute
intervals thereafter until recovery. The initial data for
ET
CO2, SpO 2, and EEG was recorded two minutes
postpropofol induction and continued at five-minute
intervals as long as the dogs would tolerate. Control
values for the EEG were not recorded due to humane
considerations and excitement artifacts in response to
placement of recording needle electrodes in
nonmedicated dogs.
The depth of anesthesia was assessed by evaluat-
ing the responses of the dogs to mechanical, noxious
stimulation by tail clamping and by assessment of the
palpebral reflexes at one-minute intervals during the
transition period. Adjustments were made in anes-
thetic concentration as needed to prevent purposeful
movement during the transition from propofol to in-
halant anesthesia. The tail clamp evaluation was per-
formed using noncrushing intestinal forceps closed to
the first rachet position for three seconds. Objective
evaluations of depth of anesthesia included the dis-
play and recording of brain wave activity using a
compressed spectral analysis (CSA) computer-as-
sisted EEG monitor-recorder; h data was stored on a
computer disk for further analysis at a later time. Five
platinum electrodes were used. One reference and
one active electrode were placed subcutaneously on
each side of the head in contact with the skull over
each cerebral hemisphere, with the fifth electrode
placed over the central fissures between the eyes as a
ground. 8 Quantitative measurements recorded in-
cluded total amplitude expressed in microvolts, total
amplitude distribution into five frequency bands, and
the spectral edge (95% in this study). Ninety-five
percent spectral edge frequency is the frequency be-
low which 95% of the total activity occurs.
The anesthetic vaporizer was turned off after 30
minutes of anesthesia. The rebreathing bag was com-
pressed and emptied into the scavenger system and
refilled with O 2 to reduce the reservoir of anesthetic
vapor. Each dog was disconnected from the breathing
86 JOURNAL of the American Animal Hospital Association
Figure 1—Duration of anesthesia and recovery time. Inhalant
anesthetic was started two minutes after propofol induction and
continued for 30 minutes. No significant differences in duration
of anesthesia nor recovery times were observed.
system within five minutes of discontinuing anes-
thetic administration. The endotracheal tube was left
in place until adequate reflexes to protect the airway
were observed.
Statistical analysis was performed with a 5.0 Excel
program. i For cardiopulmonary and neurological data
within the group, two-way analysis of variance
(ANOVA) in a repeated-measures design was used.
One-way ANOVA was performed for each cardiovas-
cular and neurological variable between groups. The
probability value was set at p less than 0.05. Where
significant F values were encountered, analysis was
continued by calculating contrast using the Bonferroni
test. Results are reported as mean±standard deviation (SD).
Results
No significant metabolic and hematological abnor-
malities were recorded in the 12 dogs. In both groups,
induction of anesthesia was not only rapid but also
smooth and without excitatory effects (e.g.,
hypertonus, myoclonia, involuntary movements). No
cases of abnormal salivation or vomiting were ob-
served. Intubation was easy and without complica-
tions. During the period considered as general
anesthesia (propofol or inhalant), none of the 12 dogs
responded adversely to the tail clamp stimulus. In-
creases were made in anesthetic concentration when
minor muscle responses to noxious stimuli were ob-
served, whereas small reductions were made if there
was no response. The first signs of arousal from anes-
thesia were tail movement and head lift. Sternal re-
cumbency and recovery were not associated with any
excitement or other complications. All dogs appeared
friendly, curious, and interested in their surroundings
immediately after standing.
January/February 1998, Vol. 34
Inhalant anesthesia was started deliberately two
minutes after propofol induction and maintained for
30 minutes. Since the inhalant agent was withheld for
the first two minutes of propofol anesthesia to obtain
comparative data, higher initial vaporizer settings
were necessary to avoid arousal during transition.
The comparative duration of anesthesia was consid-
ered to be the period of time between the end of the
propofol bolus for induction and the positive response
to the tail clamping or any spontaneous body movement.
Similar head lift, sternal recumbency, and recov-
ery times were observed in groups H and I [Figure 1].
Duration of anesthesia in group I (39.5±4.9 min) was
shorter than but not statistically different from group
H (43.2±3.9 min). Total recovery in all dogs was
observed within 60 minutes after propofol induction
(48.3±4.1 and 49.2±8.5 min in groups H and I, re-
spectively). All dogs were able to walk within 20
minutes after sufficient arousal from anesthesia for
extubation.
In both groups, propofol (6.6 mg/kg body weight,
IV) provided adequate anesthesia for easy intubation.
Mean values for the end-tidal anesthetic concentra-
tions during the 30 minutes of general anesthesia
were 1.17±0.31% and 1.13±0.30% for groups H and
I, respectively. Minimum and maximum values in
group H were 0.53±0.15% and 1.38±0.25%, respec-
tively, at five and 20 minutes. In group I, these values
were 0.54±0.23% at five minutes and 1.33±0.15% at
20 minutes. No significant differences in anesthetic
concentrations were observed within each group nor
between the two groups [Figure 2A] during the 30
minutes of anesthesia.
Neurological responses were evaluated both sub-
jectively and objectively to maintain equipotent lev-
els of halothane and isoflurane to provide desirable
analgesia and anesthesia. The total amplitude of brain
wave activity was depressed most in the propofol/
isoflurane group. The total amplitude of the EEG in
group H was considerably higher than group I
throughout the entire anesthetic procedure [Figure
2B]. In both groups, an increase in total amplitude of
brain wave activity followed the change from propofol
to inhalant. Spectral edge frequencies in group H
shifted toward faster frequencies by 10 minutes after
propofol induction. In contrast, spectral edge frequen-
cies in group I had the tendency to decrease signifi-
cantly to slower bands after transition to the inhalant
[Figure 2B].
A temporary increase in pulse rates occurred in
both groups after propofol induction. The maximum
rates were 113±9.4 beats per minute at two minutes in
group H and 101.2±21.7 beats per minute at five
minutes in group I. Progressive decreases in pulse
rates then were observed during inhalant anesthetic
maintenance, with insignificant differences between
January/February 1998, Vol. 34
Figures 2A, 2B—Inhalant anesthetic requirements and related
neurological responses: (A) end-tidal anesthetic concentration;
(B) total amplitudes and spectral edge frequency response.
groups. Significant differences were measured within
group H versus the preinduction control value [Fig-
ure 3A].
Mean arterial blood pressure decreased after the
first 10 minutes of anesthesia in both groups and then
stabilized between 54 and 61 mmHg. Mean arterial
blood pressure increased during early anesthetic
arousal. The lowest blood pressures recorded were
54±12.8 mmHg and 56.7±9.4 mmHg in groups H and
I, respectively. Significant differences were observed
within the two groups versus the preinduction control
values, but significant differences were not observed
between the two groups. Prior to the administration
of either halothane or isoflurane, there were no sig-
nificant differences in blood pressures between the
groups [Figure 3B].
Although ventilation was depressed during
propofol induction, no dogs developed apnea. The
Propofol 87
Figures 3A, 3B—Comparative cardiovascular responses: (A)
heart rate; (B) mean arterial blood pressure. Heart rates in-
creased after propofol in both groups. This was significant in the
halothane group (group H) at two minutes compared to control.
Heart rates then were slower in both groups, but only in the
halothane group was this of statistical significance compared to
control. The blood pressure values show a significant reduction
in both groups during either halothane or isoflurane anesthesia
compared to controls. Propofol did not cause a significant
reduction in blood pressure. Differences between groups were
not significant.
respiratory rate was affected by propofol administra-
tion within the first minutes of general anesthesia.
The frequency was 68.3% (group H) and 80.8% (group
I) less than control values at two minutes after
propofol induction [Figure 4A]. End-tidal alveolar
carbon dioxide (CO2 ) concentrations were consis-
tently within normal ranges during the entire anes-
thetic period in both groups. The maximum level was
41±2 mmHg observed at 30 minutes of anesthesia in
group H and 42±3.8 mmHg recorded two minutes
after propofol induction in group I. Statistically sig-
nificant differences are shown in Figure 4B.
Mean SpO 2 remained greater than 90% in both
groups at two and five minutes after induction. How-
ever, in group H, one dog had SpO 2 values of 85%
88 JOURNAL of the American Animal Hospital Association
Figures 4A, 4B, 4C—Comparative pulmonary responses: (A)
respiratory rate; (B) end-tidal carbon dioxide (CO2); (C) oxygen
(O 2) saturation. The influence of propofol induction reflects a
lower respiratory rate and O2 saturation (SpO2 ) level. Apnea was
not observed. Mean SpO 2 was greater than 90%. Lower SpO 2
values were observed in some dogs as individual variations
from propofol respiratory depression during the first five minutes
of anesthesia.
January/February 1998, Vol. 34
and 78% at two and five minutes, respectively,
whereas a second dog had a SpO2 value of 85% at two
minutes. In group I, one dog had a SpO 2 value of 76%
at two minutes, whereas a second dog had a value of
81% at five minutes. During this time, the dogs were
receiving O 2 from the anesthetic unit. After five min-
utes, dogs receiving halothane showed a greater and
more rapid increase in SpO 2 than the dogs anesthe-
tized with isoflurane. The respiratory pattern observed
in group I was stable. The lowest (91.7±5.3%) and the
highest (97.2±0.8%) SpO 2 values were reached by
group H at two and 10 minutes, respectively. A statis-
tical difference between groups was observed at 10
minutes [Figure 4C].
Discussion
The present study was designed to determine the
physiological changes occurring during anesthesia
that was induced with propofol and maintained with
either halothane or isoflurane. Secondly, the authors
wanted to determine the required alveolar concentra-
tion of halothane or isoflurane that would prevent
changes in brain activity and purposeful movement in
response to noxious stimuli as objective and subjec-
tive evaluations during the transition from propofol
to inhalant anesthesia.
The pharmacokinetics of propofol confirm a rapid
distribution phase, rapid elimination, and lack of ac-
cumulation with repeated administration. It is a use-
ful agent, either as an intravenous agent for the
induction of anesthesia maintained by inhalation
agents or for injectable anesthesia with or without
premedicants.9–12 The recovery from propofol is sig-
nificantly faster than the recovery from thiobar-
biturates. As a result, the vaporizer should be turned
on immediately after intubation, and inhalant anes-
thetic should be administered to prevent arousal from
propofol before adequate anesthesia is achieved.
The induction dose (6.6 mg/kg body weight, IV) of
propofol in dogs was determined in a preliminary
study in the authors’ laboratory. This dose of propofol
in unpremedicated dogs confirms the dose (6.55 mg/kg
body weight) reported by Morgan (1989). 1 Beyond
dose requirements, use of a new anesthetic for the
first time requires a period of adaptation and famil-
iarization for ease of administration. All anesthetics
have potential adverse effects at relatively high doses
or concentrations. Apnea is the most common adverse
effect related to the administration of propofol. The
incidence of apnea can be affected by the dose of
propofol or speed of administration. If the adminis-
tration of propofol is too rapid, it can cause apnea or
vomiting. 13 However, if the administration of propofol
is too slow, it may not provide adequate induction of
anesthesia due to rapid redistribution and metabo-
lism. Propofol should be administered to effect, after
selecting an appropriate dose based on premedica-
January/February 1998, Vol. 34
tion, temperament of the patient, and speed of injec-
tion. Injecting propofol as rapidly as thiobarbiturates
to prevent excitement is not necessary. Propofol (6.6
mg/kg body weight, injected over 60 sec) safely in-
duced recumbency for five-to-eight minutes; endotra-
cheal intubation was easy, and there were no side
effects in this study. Proper administration effectively
prevents apnea, yet induces general anesthesia. As
shown in the literature,14 the respiratory depression
of propofol can be similar to that seen with other
intravenous agents. However, the authors have not
observed cardiac dysrhythmias associated with
propofol unless prolonged respiratory depression has
been allowed. In this study, the drop in respiratory
rate within two minutes after propofol administration
was 74.6%, calculated as a mean for both groups.
This is probably due to transient depression of the
respiratory centers. Mean values for oxygen satura-
tion were lower during the first five minutes of
propofol anesthesia than later during the maintenance
period with the inhalant anesthetics.
Preanesthetics were not used in this trial. Changes
in blood pressure were influenced only by propofol
and the inhalant anesthetics. Both propofol and inha-
lants depress cardiovascular function. The cardiovas-
cular effects of propofol have been measured in
several studies. Systemic blood pressure decreased
due to vasodilatation15 and cardiac output and stroke
volume also decreased. 16 Nevertheless, Goodchild, et
al. 17 considered the cardiac output decrease to be the
result of reduction in preload by a direct venodilation.
In the authors’ study, propofol (6.6 mg/kg body
weight, IV), which was the only agent used during the
first two minutes of anesthesia, decreased the mean
arterial blood pressure by 14.1% in group H and by
1.1% in group I. The average decrease in all 12 dogs
was 7.6% two minutes after propofol induction. This
observed decrease was influenced by a marked drop
(21.4% in group H and 18.2% in group I) in diastolic
blood pressure. After administration of inhalants, this
trend continued until mean blood pressure stabilized
at 15 minutes. The maximum decreases from awake
control values in group H and group I were calculated as
52.4% and 38%, respectively. A slight increase in blood
pressure occurred as the inhalants were discontinued.
In this study, intravenous fluids or medications to
control blood pressure were not administered. It has
been reported 18 that isoflurane, at similar anesthetic
concentrations, permits better cardiac function than
halothane; it induces less negative cardiac inotropism
through a differential alteration of intracellular cal-
cium (Ca ++) stores. Since the cardiac output was not
measured, the authors could not confirm this finding.
This study was designed to measure the principal
cardiovascular variables used in clinical veterinary
practice and to develop a safe and reliable anesthetic
Propofol 89
protocol in the dog. An insignificantly lower blood
pressure was observed during halothane administra-
tion compared to isoflurane administration. This dif-
ference is believed to be due to the cardiodepressant
effect of halothane as an anesthetic and the concen-
tration of halothane administered.
The heart rate response observed did not seem to
be coupled to the decrease in blood pressure; perhaps
the baroreceptor sensitivity was depressed or reset by
the combined effect of propofol and inhalant agents.
After an initial increase in heart rate, a progressive
drop below the baseline values was observed; it was
statistically significant in group H.
The minimum alveolar anesthetic concentration
(MAC) of an inhalant anesthetic is that concentration
which prevents purposeful movement in response to
noxious stimuli in 50% of patients. The MAC is de-
fined in terms of percentage of one atmosphere, and it
will indicate the alveolar anesthetic partial pressure.
Several investigators have determined the MAC values
for both halothane and isoflurane in unpremedicated
dogs. These values range between 0.87% to 1.04%
for halothane and 1.20% to 1.39% for isoflurane. 5,19
In the authors’ study, the MAC requirements follow-
ing the administration of propofol for induction of
anesthesia without any premedication were 1.17±0.31%
for halothane and 1.13±0.30% for isoflurane. There
was no statistical difference between groups.
The MAC values were influenced by three factors:
1) rapid and significant recovery from propofol in-
duction occurs in five-to-eight minutes; 2) the solu-
bility and blood-gas coefficients for halothane and
isoflurane favor faster onset of isoflurane anesthesia;
and 3) concentrations that could minimize movement
in response to noxious stimuli in all dogs were ad-
ministered as would be expected in clinical practice.
It is anticipated that after the transition from propofol
to inhalant anesthesia in clinical practice, further ad-
justments in concentration will be made relative to
the established potency of the inhalant agent and the
requirements of the individual patient.
Although not used routinely in veterinary clinical
practice, compressed spectral analysis in anesthetic
research of brain wave activity offers advantages over
other methods of evaluating brain function. It is a
noninvasive method, does not require radioactive sub-
stances, and it gives objective evaluations of cerebral
activity during anesthesia.
Two methods (i.e., total amplitude and spectral
edge) of gauging the correlation of neurological re-
sponses to anesthetics and analgesics were used. Syn-
chronization or desynchronization of cortical
electrical activity results in changes in the total am-
plitude during the EEG recordings. Very deep anes-
thesia may cause a decrease in the large EEG
amplitude during sleep or surgical anesthesia due to
90 JOURNAL of the American Animal Hospital Association
depression of cortical neuronal activity. Pain stimula-
tion may cause a change from the slower and lower
amplitude to higher frequencies. Spectral edge fre-
quency is the frequency below which a certain per-
centage (95%) of the total power (amplitude) is
located. Shift in the power spectral edge allows the
investigator to determine and pinpoint frequency
shifts in brain wave activity due to anesthesia or the
presence of surgical stimulation.20
In this study, the EEG recordings provided clear
evidence, when coupled with subjective responses to
painful stimuli, that adequate anesthesia was achieved
in both groups. Induction of anesthesia with propofol
initially depressed brain wave activity. The total am-
plitude showed a consistent numerical difference be-
tween groups H and I, especially at the 10-minute
reading which was significant statistically. This dif-
ference can be explained by the fact that isoflurane
depresses the cortical electrical activity more effec-
tively than halothane at equipotent alveolar concen-
trations. 21 Also, it has been demonstrated in dogs that
isoflurane, at different multiples of MAC, does not
produce a significant increase in cerebral blood flow
or cerebral vascular resistance compared to hal-
othane. 22,23 Isoflurane, because of its depressant ef-
fect on cortical electrical activity, can provide some
cerebral protection by reducing the cerebral meta-
bolic rate for oxygen (CMRO 2).21 It has been proven
that increases in CO 2 significantly can affect the quan-
titative EEG and the brain wave activity interpreta-
tion. 24 In this study, however, both groups had
physiological levels of CO2 (eucapnia) throughout
anesthesia, and the authors believe that the influence
of CO 2 was minimal.
Recovery time (determined by times to head lift,
sternal recumbency, and walking) was similar in both
groups. Zbinden, et al. 25 demonstrated that the rates
of elimination of halothane or isoflurane from brain
tissue and from blood were similar in dogs. The abil-
ity to walk returned quickly and was characterized by
excellent coordination and minimal ataxia.
Conclusion
Propofol (6.6 mg/kg body weight, IV) given over 60
seconds to unpremedicated dogs produced safe,
smooth, reliable anesthetic induction without adverse
effects. The ventilatory depressant effects of propofol
were recognized, but they are manageable in clinical
practice. Propofol-inhalant anesthesia can be achieved
best by early intubation and administration of the
inhalant following induction with propofol. The ab-
sence of uncontrolled side effects in this study sup-
ports the conclusion that propofol is an effective IV
drug for induction of anesthesia and that it is compat-
ible with commonly used inhalant anesthetics in dogs.
Even though halothane and isoflurane depress cardio-
January/February 1998, Vol. 34
vascular function in a dose-dependent manner, the
changes in heart rate and blood pressure were not
significant in this study.
a
Rapinovet; Mallinckrodt Veterinary, Inc., Mundelein, IL (now Schering
Plough, Union, NJ)
b
Halothane; Halocarbon Laboratories, North Augusta, SC
c
Isoflurane, Isoflo; Solvay Animal Health, Inc., Mendota Heights, MN
d
Narcovet 2 Small Animal Anesthetic Unit; North American Drager, Inc.,
Telford, PA
e
POET Monitor; Criticare Systems, Inc., Milwaukee, WI
f
Datascope Model 870/821A; Datascope, Inc., Paramus, NJ
g
Dinamap Model 1255; Critikon, Inc., Tampa, FL
h
Biologic Traveler 302/PJ-1080A Printer; Biologic, Inc., Mundelein, IL
i
5.0 Excel; Microsoft Corporation, Redmond, WA
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