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Echocardiographic Assessment of Cardiac Structure and Function in Great

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ECHOCARDIOGRAPHY IN GREAT APES 1

Int. Zoo Yb. (2014) 48: ••–••

DOI:10.1111/izy.12026

Echocardiographic assessment of cardiac

structure and function in great apes:
a practical guide
R. SHAVE1*, D. OXBOROUGH2, J. SOMAUROO3, Y. FELTRER4, T. STRIKE4,
A. ROUTH5, S. CHAPMAN6, S. REDROBE6, L. THOMPSON6, S. UNWIN7, G. SAYERS8,
H. MURPHY9, G. RAPOPORT10 & E. STÖHR1
1
Cardiff Metropolitan University, Cyncoed Campus, Cardiff CF23 6XD, United Kingdom,
2
Liverpool John Moores University, Liverpool L3 2AJ, United Kingdom, 3Countess of
Chester Hospital, Heath Park, Chester CH2 1UL, United Kingdom, 4Zoological Society of
London, Regent’s Park, London NW1 4RY, United Kingdom, 5Durrell Wildlife Conservation
Trust, Les Augrès Manor, La Profonde Rue, Trinity, Jersey JE3 5BP, Channel Islands,
6
Twycross Zoo, East Midland Zoological Society, Atherstone, Warwickshire CV9 3PX, United
Kingdom, 7Chester Zoo, Upton-by-Chester, Chester CH2 1LH, United Kingdom, 8Paignton
Zoo Enviromental Park, Totnes Road, Paignton, Devon TQ4 7EU, United Kingdom, 9Zoo
Atlanta, 800 Cherokee Avenue, Atlanta, Georgia 30315, USA, and 10College of Veterinary
Medicine, University of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USA
E-mail: rshave@cardiffmet.ac.uk

Cardiac disease has been implicated as a leading cause INTRODUCTION

of death in captive great apes. Trans-thoracic echocardi-
ography provides clinically relevant information that
may help differentiate between the myriad of different
heart diseases and disorders, guide treatment and aid the
management of great apes with underlying cardiac
pathology. The purpose of this paper is to provide an
outline of the procedures and methodologies required to
conduct a thorough trans-thoracic echocardiogram of
great apes under general anaesthesia. Basic logistical
considerations are discussed before a detailed descrip-
tion of the procedures required for the assessment of
overall cardiac structure and function. Using a thorough
systematic approach, it is our belief that veterinary pro-
fessionals may be better able to diagnose, treat and
manage captive great apes with, or at risk of developing
heart disease.
Key-words: cardiac function; diagnosis;
echocardiography; great ape; health; heart disease;
monitoring; ultrasound.
Heart disease has been widely reported
as a major cause of mortality in captive great
ape populations (Schmidt, 1975; Munson
& Montali, 1990; Meehan & Lowenstein,
1994; Seiler et al., 2009; McManamon &
Lowenstine, 2012). However, ‘heart disease’
is an umbrella term that encompasses a
variety of congenital and acquired diseases
that differ considerably in their symptoms
and phenotypical expression. For example,
previous authors have reported evidence of
aortic dissection (Kenny et al., 1994), inter-
stitial myocardial fibrosis (Lammey et al.,
2008), dilated cardiomyopathy (Sleeper
et al., 2005), hypertension with subsequent
heart failure (Miller et al., 1999) and

*Correspondence: Professor Rob Shave, Cardiff Metropolitan University, Cyncoed Campus, Cardiff CF23 6XD, UK.
E-mail: rshave@cardiffmet.ac.uk

Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
2 THE DEVELOPING ZOO WORLD
atherosclerotic heart disease (Manning,
1942; Scott et al., 1995) in great apes. In
order to initiate appropriate intervention, it is
essential that veterinary professionals are
able to make an appropriate diagnosis of the
specific type of ‘heart disease’ that is present.
While cardiac ultrasound is the initial
diagnostic tool of choice in the assessment of
cardiac structure and function in humans, to
date only limited data on cardiac function
in great apes are available. Recently, in an
attempt to characterize normal cardiac struc-
ture and function in Western lowland gorilla
Gorilla gorilla gorilla in captivity within
the USA, Murphy et al. (2011) reported the
initial echocardiographic findings from the
Great Ape Heart Project. This novel study
reported data for left ventricular (LV) wall
thickness, LV cavity dimensions, LV ejection
fraction (LVEF) and aortic root diameter
in 66 apparently healthy adult gorillas.
Although echocardiographic assessment of
basic LV structure and global measures of
cardiac function [e.g. ejection fraction (EF)]
is informative, a more comprehensive cardiac
assessment is likely necessary in order to
identify and distinguish the different cardiac
pathologies that have been reported in great
apes. In order to ensure accuracy and repro-
ducibility of findings, echocardiographic
examinations require adherence to standard-
ized protocols, which if not followed can
result in off-axis image acquisition, erro-
neous measurements and inappropriate clini-
cal interpretation. The purpose of this paper
is to outline the procedures associated with
a comprehensive trans-thoracic echocardio-
graphic examination in great apes under
general anaesthesia.
INTRODUCTION TO
ECHOCARDIOGRAPHY IN
GREAT APES
Trans-thoracic echocardiography (TTE) is a
well-established cardiac imaging modality
with many applicable indications (Cheitlin
et al., 2003). As a diagnostic tool, TTE is
considered safe (Barnett, 2001) and there are
no direct contraindications (Cheitlin et al.,
Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
2003). Ultrasound equipment is now widely
available and the cost is becoming less pro-
hibitive. Furthermore, new portable versions
are available that provide a high degree of
flexibility, enabling comprehensive assess-
ments to be carried out in a variety of envi-
ronments. This often means that animals can
be assessed without the additional health-
and-safety issues associated with transporta-
tion. The procedures outlined in this paper
are based upon established guidelines for the
assessment of cardiac structure and function
in humans, and have been modified, where
appropriate, through the authors’ work with
great apes. In our experience, and using
trained sonographers, it is possible to
complete a comprehensive echocardiogram
within c. 10–20 minutes. Throughout the paper,
example images from healthy animals are used
to help explain procedures. As normal data
regarding cardiac structure and function for
great apes are extremely limited at present, the
use of pathologic examples has been avoided;
however, in time it will likely be prudent to
discuss and characterize individual cardiac
pathologies that are evident within populations
of great apes.
A SYSTEMATIC APPROACH
Discussion of anaesthetic protocols in great
apes, although important when interpreting
the echocardiographic findings, is beyond the
scope of this paper, and the procedures that
follow assume that a stable anaesthesia has
been established. Ideally the examination is
conducted with the animal in left lateral
recumbency (Plate 1A) as this causes the
heart to move closer to the chest wall and,
hence, closer to the transducer. However,
where body size or unstable respiration
restrict positioning, it is often possible to
conduct a thorough evaluation with the
animal in dorsal recumbency (Plate 1B). In
order to maximize the echocardiographic
acoustic windows, positioning the animal’s
left arm above the shoulder is also beneficial
if practicable. Multiple transducers are avail-
able for any given ultrasound machine, each
typically possessing a range of frequency
ECHOCARDIOGRAPHY IN GREAT APES 3

Plate 1. A. Lateral recumbency may be achieved using straw packing, foam wedges or manual assistance. B.
Dorsal recumbency, although not ideal, often allows for adequate image acquisition if the size of animal,
examination location or unstable anaesthesia does not permit the use of the lateral position. The sonographer
may wish to scan from either the right or left side of the animal dependent upon what they are comfortable with.
Rob Shave, International Primate Heart Project, Cardiff Metropolitan University.

options depending on the manufacturer.
Transducer selection depends on the proxim-
ity of the heart to the transducer, the avail-
ability of acoustic windows, and the nature
and focus of the examination. We have found
that a standard adult human transducer (e.g.
2–5 MHz) provides an acceptable balance
between tissue penetration and image resolu-
tion in animals ranging from large 웧
silverback Gorillas Gorilla gorilla to small 웨
Bonobos Pan paniscus. However, it is pos-
sible that in very small juvenile animals, a
higher-frequency (e.g. 4–7·5 MHz) trans-
ducer may provide adequate penetration and
superior resolution. It should be noted that
large body size, excessive fat, chest-wall
abnormalities and pulmonary disease may all
reduce image quality. Nonetheless, it is
usually possible to gain diagnostic images
even in animals where a full data set cannot
be obtained. All digital acquisition is coupled
to a single-lead electrocardiogram (ECG)
inherent to the ultrasound system, which
enables the identification of specific time
components within the cardiac cycle. It is,
therefore, important to ensure good-quality
ECG capture. We have found that attaching
adhesive ECG electrodes to the hands and
feet of the animals provides the most reliable
signal, and avoids the necessity to shave,
although the use of crocodile clips is also
viable. The diagnostic use of ECGs in great
apes is outside the scope of this paper;
however, as part of a comprehensive cardio-
vascular examination, similar to humans, a
12-lead ECG likely provides additional diag-
nostic data.
OVERVIEW OF
ECHOCARDIOGRAPHIC MODALITIES
A complete TTE investigation includes
the use of two-dimensional (2D), motion
(M-mode) and Doppler ultrasound modali-
ties. The information provided by these is
complementary, and their combined use
is necessary for a complete examination,
yielding far greater sensitivity and speci-
ficity in the assessment of cardiac disease
(Oxborough, 2008). The following sections
provide a brief summary of the main

Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
4 THE DEVELOPING ZOO WORLD

Plate 2. Parasternal long-axis views at: A. end diastole and B. end systole. It should be noted that measurements
of wall thickness and cavity diameter must be taken perpendicular to the myocardium/cavity. International
Primate Heart Project, Cardiff Metropolitan University.

Plate 3. M-mode image showing a single ultrasound scan line (see B-mode image at the top of the screen) over
the course of five cardiac cycles: x. left ventricular internal diameter during diastole; y. left ventricular internal
dimension during systole; z. inter-ventricular septum during diastole; q. posterior free wall during diastole.
International Primate Heart Project, Cardiff Metropolitan University.

uses of these modalities during a typical
echocardiogram.
Two-dimensional echocardiography pro-
duces the conventional and familiar grey-
scale images characteristic of a diagnostic
ultrasound examination (Plate 2). These
images allow the visual assessment of cardiac
structure and function, which although sub-
jective, is nonetheless a critical part of any
examination. Caliper measurements per-
formed from these images, although subject
to human error, provide a more objective
means of assessment. These include both
linear measurements (e.g. wall thicknesses
and chamber dimensions) and non-linear
measurements (e.g. chamber area and volume
calculations). The real-time 2D image also
provides a visual guide for each of the other
modalities and is necessary in order to obtain
accurate and valid M-mode and Doppler
measurements.
M-mode echocardiography captures infor-
mation along a single scan line obtained
from the 2D data set (Plate 3). Using a very
high sampling rate compared with the other
modalities, the resultant display provides
high temporal resolution of structures that
can be difficult to resolve with the human

Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
ECHOCARDIOGRAPHY IN GREAT APES 5

Plate 4. Tissue Doppler image of the left lateral free wall. Note the position of the sample volume (Doppler gate)
at the mitral valve annulus in the colour B-mode image at the top of the screen: S′. systolic wall velocity; E′. early
diastolic tissue velocity; A′. late diastolic (atrial) tissue velocity. Sample volume may be placed in the septal and
right ventricular free wall to examine region specific function. International Primate Heart Project, Cardiff
Metropolitan University.

eye. Historically, M-mode has been consid-
ered the gold standard for linear distance
measurements. However, as ultrasound-image
quality has improved with technological
advancement, 2D caliper measurements have
become an acceptable and even preferred alter-
native for this purpose.
Applying the Doppler shift principle to
compare sent and returning ultrasound wave
frequencies, Doppler-based imaging is used
to obtain velocity data as well as crude direc-
tional information. For the purposes of diag-
nostic ultrasound imaging, it can be divided
into spectral Doppler and colour Doppler
imaging, and either of these can be applied to
blood flow or myocardial tissue.
Spectral Doppler-derived information,
most commonly presented as yellow wave-
forms such as in Plates 4 and 5, is obtained
via either pulsed-wave (PW) or continuous-
wave (CW) interrogation. Using a Doppler
sample gate, PW Doppler focuses on a small,
specified volume of blood or tissue (e.g.
blood flow just distal to a valve). This enables
the evaluation of a specific region of interest
but is limited to relatively lower velocities
owing to the need to wait for a sent pulse to
return to the transducer before sending out
another pulse. CW Doppler can measure
higher blood velocities along a line of inter-
rogation (e.g. a stenotic left ventricular
outflow tract, or mitral regurgitant flow) but
specific localization along that line is not
possible.
To obtain accurate spectral Doppler data
for blood flow, it is essential that the ultra-
sound beam is as close to parallel with the
blood flow as possible. Each standard view
offers the opportunity for Doppler assess-
ment of certain regions of interest. Proper
alignment can be optimized by movement of
the transducer and, if necessary, the animal.
For both PW and CW Doppler, flow towards
the transducer is graphically presented
above the baseline while flow away is below.
Spectral Doppler-derived flow velocity infor-
mation is expressed in units of either centi-
metres or metres per second. When applied to
fluid (in this case blood), this can be con-
verted into quantitative pressure information
via a relatively simple formula (the modified
Bernoulli equation), which is invaluable in
the haemodynamic assessment of the heart
and the great vessels. Conditions such as

Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
6 THE DEVELOPING ZOO WORLD

Plate 5. Transmitral Doppler. Note the Doppler sample volume (Doppler gate) in the B-mode image at the top
of the screen, positioned immediately caudal to the mitral valve: E. early ventricular filling velocity; A. late
(atrial) ventricular filling velocity. It should be noted at higher heart rates >100 beats minute−1 the E and A waves
often fuse into a single waveform. International Primate Heart Project, Cardiff Metropolitan University.

valvular stenosis and pulmonary hyperten-
sion can be diagnosed and graded for severity
using spectral Doppler imaging.
The application of Doppler imaging to
tissue (commonly referred to as tissue
Doppler imaging, or TDI) has primarily
focused on the assessment of diastolic
cardiac function, although information about
systolic function can also be acquired. This
technique is somewhat newer than the evalu-
ation of blood flow and has received much
attention in the human cardiology field.
However, to date the use of TDI in veterinary
medicine has been limited primarily to cats
and dogs and requires further examination in
other species. To the knowledge of the
authors its use in great apes has not been
evaluated but, given the significant utility
within human medicine, TDI methodology is
discussed below.
Colour Doppler imaging is a form of
multi-gated PW Doppler imaging, in which
colour is assigned to many different regions
of interest and overlaid on a 2D image.
Coupled with knowledge of normal cardiac
anatomy and blood-flow patterns, it is most
commonly utilized in the assessment of blood
flow for abnormal direction and/or lack of a
normal laminar flow pattern (i.e. flow turbu-
lence). Various colour maps may be used,
with one common map assigning the colour
blue to blood moving away from the trans-
ducer and the colour red to blood moving
towards the transducer. The inclusion of
‘variance’ in a colour map is used to indicate
multi-directional flow, which is inferred to
represent flow turbulence. Colour Doppler
imaging is a sensitive tool for detecting
valvular regurgitation, septal defects and
other abnormalities resulting in blood-flow
turbulence.
The order in which images are acquired
during an echocardiogram is not important;
however, a systematic approach is recom-
mended to ensure that all required images are
acquired. Normally, most images can be
obtained from two distinct acoustic windows.
In humans and, in our experience, generally in
great apes, the parasternal window is typically
positioned in either of the third or fourth inter-
costal spaces against the left sternal border
(Plate 6A), whereas the apical window is typi-
cally located in the sixth or seventh intercostal
spaces in the mid-axilla (Plate 6B). Depend-
ent on size and individual anatomy, the spe-
cific rib spaces for these windows may vary

Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
ECHOCARDIOGRAPHY IN GREAT APES
Plate 6. Transducer positions to acquire: A. parasternal and B. apical trans-thoracic echocardiographic images
in great apes. Rob Shave, International Primate Heart Project, Cardiff Metropolitan University.
slightly between animals and transducer
movement between ribs, or movement more
medial or lateral, is often required to optimize
the image.
DETERMINATION OF LV AND
RIGHT VENTRICULAR
(RV) STRUCTURE
The main purpose of assessing LV and RV
structure is to quantify absolute cardiac size.
This includes the determination of systolic
and diastolic LV and RV wall thicknesses,
internal cavity dimensions, and LV mass.
Measurements of wall thickness and cavity
dimensions are normally performed on
images obtained at end-diastole, guided by the
ECG [beginning of the QRS complex (i.e. the
principal deflection in the ECG, representing
the start of ventricular depolarization)] and
generally corresponding to the maximum
separation between the inter-ventricular
septum and left ventricular posterior wall. In
addition to standard cavity and wall-thickness
measurements, the relationships between
internal cavity dimensions and/or wall thick-
ness or between left and right chambers can
also be useful indicators of overall cardiac
structure. Although limited, Table 1 contains
LV structural data that have been collected as
Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
7
part of the Great Ape Heart Project. For com-
parison, normal human data are also pre-
sented (Lang et al., 2005).
LV and RV wall thickness and
cavity dimension
Diastolic and systolic wall thickness and
dimensions are obtained from a parasternal
long-axis image such as that shown in Plate 2.
As outlined above, the parasternal long-axis
view is ideally obtained with the animal in left
lateral recumbence. In this position, the ultra-
sound transducer is placed in the third or
fourth intercostal space against the left sternal
border with the transducer index point (notch
or light on the side of the transducer) pointing
towards the animal’s right shoulder. In order
to optimize image acquisition, subtle adjust-
ments may be required, such as tilting
(‘fanning’) and/or rotation of the transducer.
The aim is to produce an image that is aligned
with the long axis of the left ventricle,
showing the mitral valve in the centre of the
sector, the left atrium and aortic root to the
right, and the inter-ventricular septum paral-
lel to the left ventricular posterior wall. As a
result of improvements in image clarity
and temporal resolution achievable with
modern machines, recent human guidelines
 8

HUMAN+ WESTERN LOWLAND GORILLA* CHIMPANZEE** BONOBO**

웨 웧 웨 웧 웨 웧 웨 웧
ECHOCARDIOGRAPHIC
PARAMETER (n = 14) (n = 9) (n = 1) (n = 1)

Left ventricular diastolic 39–53 42–59 44 (35–53) 56 (32–75) 45 (36–56) 45 (32–59) 39 41

diameter (mm)
Interventricular septum 6–12 6–13 12 (7–20) 14 (8–23) 10 (8–13) 10 (6–16) 6 4
(mm)
Left ventricle posterior 6–12 6–13 12 (8–24) 14 (10–20) 9 (6–12) 8 (6–10) 4 7
wall (mm)
Left ventricle diastolic 56–104 67–155 73 (41–129) 76 (58–97) 38 70
volume (ml)
Left ventricle systolic 19–49 22–58 36 (22–48) 30 (18–50) 17 31
volume (ml)
Relative wall thickness <0·45 <0·45 0·44 (0·31–0·56) 0·43 (0·29–0·63) 0·26 0·27
Left ventricular ejection >55 >55 65 (44–82) 62 (50–80) 48 (27–63) 60 (49–71) 56 56
fraction (%)

Table 1. Measures of left ventricular structure in great apes (mean and range presented). Data taken from previous publications (Møller et al., 2006; Lammey
et al., 2008) or as part of the ongoing Great Ape Heart Project: + indicates data taken from Lang et al. (2005); * indicates data taken from Murphy et al. (2011);
** indicates data obtained as part of the International Primate Heart Project. These values are not intended as ‘normal’ reference ranges, rather as the min–max
data that have been collected and likely includes animals with pathology.
THE DEVELOPING ZOO WORLD

Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
ECHOCARDIOGRAPHY IN GREAT APES
recommend that end-diastolic and end-
systolic LV measurements be directly
obtained from the parasternal long-axis
2D image as opposed to the previously
recommended M-mode approach (Plate 3)
(Feigenbaum et al., 2004; Lang et al., 2005).
The image is paused at end-diastole
(Plate 2A) and inter-ventricular septal thick-
ness (IVSd), left ventricular internal dimen-
sion (LVIDd) and left ventricular posterior-
wall thickness (LVPWd) are measured at the
level of the mitral-valve leaflets. End-diastole
can be defined as either the onset of the QRS
complex in the ECG (preferred approach) or,
in the absence of a simultaneous ECG, the
frame after the mitral valve closes. With slight
adjustment moving the aortic and mitral
valves more centrally into the image, left
atrial and aortic root diameters may also be
assessed from this view. Importantly, in order
to ensure accurate assessment of cardiac
dimensions, measurements must be made
in appropriately orientated standard views
(foreshortening leads to underestimation of
chamber dimensions) with the beam perpen-
dicular to myocardial walls and ventricular
chamber long axis (obliquity leads to overes-
timation). End-systolic values are obtained by
moving the parasternal long-axis recording to
the end-systolic frame (Plate 2B) within the
same cardiac cycle. The end-systolic frame
occurs immediately before mitral-valve
opening. On most ultrasound systems, con-
secutive assessment of LV diastolic and sys-
tolic dimensions will produce an automated
estimation of additional parameters such as
LV volumes and LV mass. While these have
been validated previously and may be useful
if other images cannot be obtained, LV
volumes and mass obtained with this method
must be interpreted with care (Kronik et al.,
1979). More appropriate methods to estimate
end-diastolic and end-systolic volumes, EF
and LV mass are presented below.
RV wall thickness and dimensions
The anatomical position and complex shape
of the right ventricle limit its assessment
using trans-thoracic ultrasound. Notwith-
Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
9
standing, informative clinical data can be
obtained from parasternal long-axis views
(RV wall thickness and RV outflow dimen-
sions) or modified RV-focused four-chamber
views. RV and right-atrial dimensions can
be measured from a four-chamber view
obtained from the apical window at end-
diastole and end-systole, respectively. In this
view in humans, the right ventricle appears
smaller than the left and is usually no more
than two-thirds the size of the left ventricle
in the standard apical four-chamber view.
Accordingly, if the RV size exceeds that of
the LV in this view, it is likely to be abnor-
mally enlarged (Rudski et al., 2010). At
present, normative data related to right-heart
structure is not available in great apes; how-
ever, serial assessment may be useful and
indicated if pathology is suspected.
LV volumes
If image quality permits, LV volumes should
be calculated using the Simpson’s biplane
methodology (Lang et al., 2005). Briefly, 2D
loops taken from the apical four-chamber and
two-chamber views are used (Plate 7), with
the internal cavity of the LV being traced at
end-diastole and end-systole. End-diastole
coincides with the beginning of the Q-wave
on the ECG, and end-systole can be identified
in the frame with the smallest LV cavity
cross-sectional area in both apical views,
immediately prior to mitral-valve opening.
Care must be taken not to foreshorten the
images, and also to identify and trace the
endocardial boundary clearly. Combining
data from both the four-chamber and two-
chamber views means that unlike other esti-
mates of LV volumes, such as the M-mode
guided Teichholz approach (Teichholz et al.,
1976), fewer geometric assumptions are
made, and a more accurate estimation of
mass, volumes and EF can be made.
LV mass
The calculation of LV mass may help to
discriminate between physiology and pathol-
ogy by providing evidence of hypertrophy.
10 THE DEVELOPING ZOO WORLD

Plate 7. B-Mode apical 2- (top) and 4- (bottom) chamber views during end diastole (left) and end systole (right).
White line represents end diastolic (left) and end systolic (right) volumes which are used to calculate stroke
volume and ejection fraction according to Simpson’s methodology. International Primate Heart Project, Cardiff
Metropolitan University.

However, normal values for great apes have
not been published, and LV mass would
not be expected to be similar between the
great-ape taxa. Likewise, comparison with
established human reference ranges is inap-
propriate. A number of formulas exist for the
determination of LV mass. The three most
commonly used are the method by Devereux
& Reichek (1977), the area-length formula
(Reichek et al., 1983) and the truncated ellip-
soid model (Schiller et al., 1983). All of these
methods require the acquisition of multiple
echocardiographic views as detailed in the
original publications (Devereux & Reichek,
1977; Reichek et al., 1983; Schiller et al.,
1983).
Relative wall thickness (RWT),
eccentricity and sphericity indices
In order to assess overall cardiac structure it
is useful to calculate a number of indices that
combine measures of wall thickness or cavity
dimensions. Specifically, RWT, eccentricity
index and sphericity index can all be
informative. In humans these indices are
based on the fact that ‘normal’ structure is
characterized by proportional relationships
between the LV and RV or between cavity
length and diameter.
RWT, the relationship between LV cavity
diameter (LVIDd) and LV wall thickness
(IVSd), is calculated as either:
2 × PWTd
LVIDd
or
IVSd + PWTd
LVIDd
where PWT is the posterior wall thickness.
In humans, RWT has been shown to be
an important discriminator of physiological
and pathological hypertrophy with a normal
reference cut point of 0·42–0·45 (Foppa

Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
ECHOCARDIOGRAPHY IN GREAT APES 11

Plate 8. Parasternal short-axis image of the left ventricle at the level of the papillary muscle. Left ventricular
eccentricity index is calculated as the ratio left ventricular end-diastolic diameters measured at the level of
the papillary muscles between the inter-ventricular septum and the: x. posterior-lateral wall; y. inferior and
anterior walls. International Primate Heart Project, Cardiff Metropolitan University.

et al., 2005; Lang et al., 2005). It should be
noted, however, that in conditions where both
pressure and volume overload exist (e.g.
aortic stenosis with aortic regurgitation), it is
possible to have significant LV hypertrophy
with a normal RWT. Calculation of an LV
eccentricity index (LVEI) may be helpful in
situations where RV overload is suggested by
inter-ventricular septal displacement. LVEI
is the ratio of LV end-diastolic diameters
measured at the level of the papillary muscles
between the inferior and anterior walls, and
between the inter-ventricular septum and the
posterior-lateral wall (Plate 8), with a normal
ratio close to 1 (Ryan et al., 1985). To obtain
the LV short-axis image, the transducer is
rotated 90 degrees from the long-axis view,
so that the index point is in the direction of
the left shoulder. The sphericity index (SI)
is calculated by dividing LV long axis by
the axis that perpendicularly intersects the
midpoint of the long axis measured from
the apical four-chamber view. A small SI is
indicative of an elliptical LV whereas values
closer to 1·0 suggest a spherical LV. At
present, normal values for RWT, LVEI and SI
in great apes are not available. However,
these may be useful parameters to monitor in
the serial assessment of animals undergoing
clinical investigation and treatment.
ASSESSMENT OF LV SYSTOLIC
FUNCTION
Historically the evaluation of cardiac func-
tion has focused on systolic indices, in par-
ticular the left ventricle, which has geometry
that is more amenable to assessment than the
right ventricle. Foremost among these indices
has been LVEF. While a useful starting point,
LVEF should not be considered the definitive
measure of overall cardiac function and
ideally should be considered alongside a
number of other measures, including indices
of diastolic function.
EF
EF provides some insight into global ven-
tricular performance as its calculation incor-
porates changes in both end-diastolic volume
(EDV) as well as end-systolic volume (ESV).
Specifically, LVEF represents the percentage
of EDV that is ejected from the ventricle
during systole and is calculated using the fol-
lowing formula:

Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
12
( EDV − ESV )
EF% = × 100
EDV
EF in the past has been calculated using
volumes derived from ventricular diameters
taken from M-mode assessments; however,
it is now recommended that LVEF should
be calculated from volumes derived using
the Simpson’s biplane method as described
above (Lang et al., 2005). If image clarity
does not permit adequate tracing of EDV or
ESV, then using volumes derived from linear
measurements would appear to be a prag-
matic approach, but this should be noted at
the point of reporting and these two methods
should not be used interchangeably. Although
LVEF is a useful index of global LV function,
interpretation of LVEF without accounting
for other aspects of cardiac function, such as
absolute ventricular volumes or blood pres-
sure (a surrogate of afterload), should be
effected with caution.
Ventricular systolic tissue velocities
Left and right ventricular TDI-derived veloc-
ities provide additional information related to
systolic and diastolic performance (Plate 4). As
mentioned above, TDI is a relatively new tool.
As such, it is not available on older ultrasound
systems. It has the advantage that regional LV
and RV function can be assessed. It must be
noted, however, thatTDI-derived indices of sys-
tolic function are not as load independent as
originally thought. That is, in addition to intrin-
sic myocardial contractility, measurements are
influenced by preload, afterload and translation
motion of the heart within the thoracic cavity.
Nonetheless, as with other echocardiographic
measurements, TDI velocities provide incre-
mental value when included as part of a com-
prehensive study.
TDI values are obtained with the ultra-
sound beam in line with myocardial motion.
For the assessment of LV free wall and
RV tissue velocities, the angle of the sector
width may have to be adjusted accordingly.
To ensure standardization of images and
comparability between different myocardial
regions, the sector width and imaging depth
Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
THE DEVELOPING ZOO WORLD
should be consistent between LV and RV
recordings and, if possible, held constant
between examinations. Once an appropriate
sector has been obtained, the TDI sample
volume is placed at the level of the mitral
annulus in the myocardial wall under exami-
nation. Differences between inter-ventricular
septal, LV free wall and RV free wall veloc-
ities exist in humans (Alam et al., 1999), with
the RV demonstrating considerably faster
velocities than both the septum and the LV
free wall. This differential pattern between
the LV and RV also appears to exist in healthy
Chimpanzees Pan troglodytes and Gorillas
(author observations).
ASSESSMENT OF DIASTOLIC
FUNCTION
In humans, impaired diastolic function has
been shown to be highly predictive of poor
cardiovascular outcome (Fagard & Pardaens,
2001; Møller et al., 2006) and often changes
in diastolic function precede reductions in
systolic function (Nesto & Kowalchuk,
1987; McManus & Aurigemma, 2006).
Accordingly, it is possible that timely
assessment of diastolic function may aid in
early intervention in great apes, or at least
in earlier detection of cardiac disease. Typi-
cally, at low heart rates, LV diastolic func-
tion is characterized by two phases of
ventricular filling; early (passive) and late
(related to atrial contraction). Early filling
results from initial pressure decay within the
ventricle, related to diastolic untwist during
the isovolumic relaxation period; this and
increasing atrial pressure result in a positive
pressure differential between the atrium and
the ventricle, resulting in the opening of the
mitral valve. Following a short delay, in the
healthy and non-tachycardic heart, the atria
contract late in diastole and ‘top-up’ the
ventricles. Diastolic function is assessed by
the characterization of the early and late
flow patterns of blood as it enters the ven-
tricle, and the associated movement of the
ventricular myocardium during these two
phases.
ECHOCARDIOGRAPHY IN GREAT APES
Transmitral filling
Using PW Doppler, the magnitude and
pattern of LV filling can be assessed. Using
an apical four-chamber view, the sample
volume is placed between the tips of the open
mitral-valve leaflets (Plate 5). If the ultra-
sound beam is placed in line with the blood
flow entering the LV chamber, the Doppler
signal should produce a clear envelope. In a
young healthy LV an alternating pattern of
high early diastolic (E) to low late diastolic
(A) filling velocities can be expected,
although this may vary considerably between
species, between animals and even between
cardiac cycles in an individual animal.
Furthermore, the contribution of early dias-
tolic passive filling (E) and late diastolic
atrial contraction (A) can change not only
with disease but also across the healthy
lifespan. In humans, for example, it is known
that healthy ageing leads to a gradual shift in
the E/A ratio such that the late (atrial) com-
ponent becomes more prominent and E/A
subsequently decreases (Lester et al., 2008).
It is likely, therefore, that low E/A ratios in
young animals indicate some degree of dias-
tolic dysfunction, which may precede the
onset of systolic dysfunction. Assessment
of RV diastolic function is achieved using a
similar approach across the tricuspid valve.
Diastolic tissue velocities
Diastolic tissue velocities are obtained from
the same images used for the assessment of
systolic tissue velocities as outlined above
and shown in Plate 4. Similar to the
transmitral filling pattern, the tissue Doppler
signal produces an E and A wave, and these
are annotated as E′ and A′. In line with the
normal transmitral filling pattern, the healthy
left ventricle produces a greater (more nega-
tive) E′ than A′, and in the presence of abnor-
mal transmitral filling, changes in diastolic
tissue velocities may reflect disease severity/
progression of diastolic dysfunction. Using a
combination of transmitral flow Doppler and
mitral annular TDI data, previous authors
have shown that the E:E′ ratio is a useful
indicator (surrogate) of left atrial pressure in
Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
13
humans (Ommen et al., 2000). Accordingly,
this measure may add value when interpret-
ing overall cardiac function. However, as
with many other indices, E:E′ has not, as yet,
been validated in great apes.
ASSESSMENT OF VALVULAR
COMPETENCE (REGURGITATION)
The advent of colour-flow Doppler has
allowed qualitative and semi-quantitative
assessment of valvular regurgitation, as well
as other causes of blood-flow turbulence.
While in the colour-flow Doppler setting, a
region of interest is superimposed over a
portion of the 2D image (e.g. a valve). This
provides a colour representation of the direc-
tion and mean velocity of blood flow. As
mentioned above, flow moving towards the
transducer is typically indicated by the colour
red and flow moving away is coded as blue.
Accordingly, with knowledge of the ‘normal’
pattern of blood flow across valves, it is
possible to identify areas of backflow or
regurgitation. The quantitative assessment of
regurgitant volume is complex, a description
of which is outside the scope of this paper.
Simple visual estimation of the size of the
regurgitant jet (e.g. relative to the size of the
receiving chamber) may be helpful in moni-
toring progression (Plate 9). In addition
to the assessment of valvular competence,
colour-flow Doppler is sensitive for detecting
certain congenital defects (e.g. atrial septal
defects, ventricular septal defects and patent
ductus arteriosus, among others).
ADDITIONAL CONSIDERATIONS
Scaling of measurements
Taxa of great apes differ considerably from
one another in both size and mass, Bonobos
typically weighing 30–40 kg while a large 웧
silverback Gorilla may weigh as much as
230 kg. In humans, up to 50% of the variabil-
ity in LV dimensions can be accounted for
by differences in body size (Pelliccia et al.,
1999). Despite this, scaling of cardiac param-
eters in clinical situations is still relatively
14 THE DEVELOPING ZOO WORLD

Plate 9. Example of aortic regurgitation (x) and tricuspid regurgitation (y) taken from the parasternal long-axis
and apical four-chamber views, respectively. Note the transmitral flow occurring simultaneous with the
regurgitant aortic flow (x). In line with the Blue Away Red Towards convention, the transmitral flow in the left
image is labelled red because it is directed towards the transducer and the flow exiting the left ventricle towards
the aorta in the right image is labelled blue because it is directed away from the transducer. International Primate
Heart Project, Cardiff Metropolitan University.

limited. Given the very large range of size
and mass evident across species of great
apes, it is likely that scaling of both cardiac
structure and function should be adopted.
Simple ratio-metric approaches that divide
cardiac parameters by some measure of body
size (e.g. height, mass, body surface area)
have been widely used in humans; however,
the assumption of a purely linear relationship
between the cardiac variable under investiga-
tion and the body size may not be valid. A
number of other theoretical issues have been
previously discussed regarding the inappro-
priateness of ratio-metric scaling for cardiac
variables (Dewey et al., 2008). Alternative
methods using allometric scaling approaches
have been suggested (Cornell et al., 2004).
Allometric scaling divides the variable of
interest by a body-size variable that has been
raised to a scalar exponent. This approach
has been shown to eliminate the effects of
body size upon the variable of interest and is
likely the approach that should be used to
compare cardiac parameters across and
between the great apes. At this point in time,
however, until large-scale studies have been
conducted, it is not possible to determine the
various allometric exponents that should be
employed, or indeed the ideal measure of
body size. In the meantime it is probably
best practice to report absolute values for
cardiac variables in great apes but to interpret
these alongside body-size and body-mass
characteristics.
Anaesthesia and blood pressure
As mentioned previously, it is beyond the
scope of this paper to examine the various
anaesthetic protocols that are used within the
clinical assessment of great apes. However, it
is important to understand that some anaes-
thetic agents directly influence cardiac con-
tractility, while others may influence vascular
resistance and, hence, loading conditions.
Moreover, the cardiovascular effects of dif-
ferent agents can vary dependent on the
amount of time that has passed since admin-
istration (Bloor et al., 1992; Selmi et al.,
2004). Accordingly, it is important to inter-
pret data in light of the specific anaesthetic
protocol that has been employed and the
timing of the echocardiogram relative to the
time of anaesthetic induction. While it may
not be possible to achieve consistency of
anaesthetic protocol between collections, it
should be possible to adopt a standardized
protocol within each institution and certainly
between repeat assessments so that data from
serial assessments in the same animal may at
least be compared.

Int. Zoo Yb. (2014) 48: ••–•• © 2013 The Authors. International Zoo Yearbook © 2013 The Zoological Society of London
ECHOCARDIOGRAPHY IN GREAT APES
It is prudent to note that in animals with
known cardiac pathology anaesthesia may be
contraindicated and so the collection of
echocardiograms in this fashion may not be
possible. It is possible that with appropriate
training animals may be assessed while con-
scious, which may be of use in animals where
anaesthesia is a concern, or in monitoring
animals in response to treatment. It is likely,
however, that the reliability and standardiza-
tion of such images will be less than that of
those obtained under stable anaesthesia and
would therefore need to be taken into account
when interpreting findings.
CONCLUSIONS
Similar to the assessment of cardiac structure
and function in humans, it is possible to
undertake a comprehensive trans-thoracic
echocardiographic examination in great apes.
While anaesthetic procedures and body
position may complicate examinations, or
preclude the acquisition of some images,
it is usually possible to collect a number of
acceptable images that may inform clinical
decisions regarding cardiac disease. At
present, true reference ranges for all
echocardiographic parameters are not avail-
able for each taxa of the great apes. As
cardiac disease has been highlighted as a
leading cause of death in these endangered
animals, for appropriate diagnosis and
disease management, it is imperative that
normal reference ranges are established. In
the meantime we advise against the use of
human reference values, rather we encourage
a comprehensive approach to cardiac assess-
ment that employs the many available ultra-
sound modalities to provide a thorough
description of overall cardiac structure and
function, which can then be used to inform
clinical opinion.
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revised 20 May 2013; accepted 25 June 2013