Download Acute and Chronic Heart Dilation Model

Acute and Chronic Heart Dilation Model-Induced in Goats by
Carotid Jugular A-V Shunt
Gil Bolotin, Roberto Lorusso, Hans Kaulbach, Jan Schreuder, Gideon Uretzky and
Frederik H. Van Der Veen
Cardiovascular Research Institute, Maastricht, The Netherlands
Abstract
Congestive heart failure is characterized by impaired quality of life and markedly shortened
life expectancy. There are currently many medical and surgical modalities that aim to treat
patients with heart failure, which implies the need for an animal heart failure model for the
development and testing of these therapeutic modalities. A variety of animal heart failure
models have been developed, including those in which heart failure is induced via drugs,
rapid ventricular pacing, genetic alteration, viral sources, idiopathic dilated cardiomyopathy, coronary arteries’ embolization, pressure overload, and volume overload by arteriovenous (A-V) shunt. The purpose of this study was to evaluate the acute and chronic effect
of carotid-jugular A-V shunt in goat model of heart dilation. After cross clamping of the
left carotid artery, an end-to-side anastomosis of 10 mm in diameter was performed
between the free end of the vein and the side of the artery.
A dual-micromanometer transducer conductance catheter was used to determine the volume
of the ventricle on-line, by measuring the time-varying electrical conductance of the segments of intraventricular blood. During and at the end of the eight weeks none of the animals showed signs of heart failure or distress. The acute and chronic hemodynamic changes
were demonstrated by pressure-volume loops at baseline, immediately after the shunt, and
after 8 weeks. There was an immediate rise in the LVEDV (104±27 ml) compared to the
baseline volume (75±26 ml), and eight weeks later the LVEDV reached 111±22 ml. None
of the eight goats demonstrated clinical signs of pulmonary congestion. The Swan-Ganz
and the conductance catheters that were used to monitor the heart hemodynamic changes
immediately after the creation of the A-V shunt revealed interesting results. Another advantage of the shunt model is that it is possible to evaluate the patency of the shunt by palpating blood thrill in the neck. The carotid jugular A-V shunt in goats causes significant left
heart dilation without signs of heart failure, and is reproducible with low animal mortality.
The study ended 8 weeks after the creation of the A-V shunt, leaving unanswered the question of possible heart failure development in this model after a longer follow up period.
Key words: animal heart failure model, arterio-venous (A-V) shunt, congestive heart failure, hemodynamic changes carotid-jugular A-V shunt.
Basic Appl. Myol. 9 (5): 219-222, 1999
Congestive heart failure is characterized by impaired
quality of life and markedly shortened life expectancy
[1]. Optimal medical treatment of patients with congestive heart failure improves the quality of life and survival rates, but mortality is still unacceptably high [9].
There are currently many medical and surgical modalities that aim to treat patients with heart failure, which
implies the need for an animal heart failure model for
the development and testing of these therapeutic modalities. A variety of animal heart failure models have
been developed, including those in which heart failure is
induced via drugs [5], rapid ventricular pacing [13], genetic alteration [10], viral sources [6], idiopathic dilated
cardiomyopathy [4], coronary arteries’ embolization [8],
pressure overload [2], and volume overload by arteriovenous (A-V) shunt [3]. The A-V shunt model induces
left heart dilation that mimics the clinical situation in
patients with dilated cardiomyopathy [11].
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Acute and chronic heart dilation model-induced in goats by carotid jugular A-V shunt
played a typical phasic LV volume tracing. A Leycom
Sigma-5DF signal conditioner-processor (CardioDynamics, Zoetermeer, The Netherlands) provided the current source and processed the segmental conductance,
producing an on-line display of the LV contours, as well
as continuous and instantaneous volume signals. The
volume signals were combined with the pressure signals
on an X-Y oscilloscope to provide an instantaneous and
uninterrupted display of pressure-volume loops.
Readings of the volume signal were corrected to account for the parallel conductance caused by tissues surrounding the ventricular cavities. A bolus of 7.5 ml of
hypertonic NaCl (9%) was injected into the central venous compartment via the Swan-Ganz catheter. As the
bolus mixed with the fluid in the ventricular cavity, its
conductivity increased, causing the overall conductance
signal to increase while the parallel component remained constant. End-systolic overall conductance was
then plotted as a function of end-diastolic overall conductance during the mixing of the bolus; the conductance was equal to the intersection point between the
regression line of these values and the line of identity.
The purpose of this study was to evaluate the acute
and chronic effect of carotid-jugular A-V shunt in goat
model of heart dilation.
Methods
Experiments were performed in eight female goats,
weighing 51 to 80 kg, in accordance with the Guide for
the Care and Use of Laboratory Animals published by
the National Institutes of Health (NIH publication 8623, revised 1985).
Dilated cardiomyopathy was induced by a left carotid
jugular A-V shunt. The acute and chronic hemodynamic
changes were followed for 8 to l0 weeks by three different monitoring modalities: Swan-Ganz catheters measured cardiac output before, immediately after the creation of the A-V shunt, and 8 weeks later; conductance
catheters measured left ventricle dimensions and performance before, immediately after the creation of the
A-V shunt, and 8 weeks later; and echocardiography
was performed before and every two weeks after the AV shunt operation.
A-V shunt procedure
General anesthesia was induced by thiopental sodium
(Pentothal, Abbott S.P.A., Italy), administered intravenously at 15 mg per kg body weight, and maintained
after endotracheal intubation with oxygen/nitrous oxide
(1:2) and 1.5% Fluothane (Halothane, Zeneca Ltd.,
Macclesfield, Cheshire, UK).
During the experiments, the lungs were ventilated
with a positive pressure respirator (Harvard, Apparatus
Inc., South Natick, Massachusetts) and body temperature was kept constant with a heating mattress. A single
dose of 10.000 IU heparin i.v. was administered.
Through a cervical incision, the left jugular vein and the
left carotid artery were mobilized over a length of approximately 5 cm and ligated distally. After crossclamping of the left carotid artery, an end-to-side anastomosis of 10 mm in diameter was performed between
the free end of the vein and the side of the artery, using
6-0 polypropylene non-absorbable running sutures
(Ethicon, Edinburgh, Scotland). Clamps were removed
and the patency of the fistula was visually confirmed by
the pulsatile filling of the jugular vein.
Results
During and at the end of the eight weeks none of the
animals showed signs of heart failure or distress.
One animal died three weeks after the A-V shunt operation most probably due to lung infection.
The carotid-jugular A-V-shunt induced both immediate and long-term hemodynamic changes. The immediate effect of the shunt, an abrupt rise in cardiac output,
was observed within 30 minutes after opening of the
shunt and measured by Swan-Ganz thermodilution
technique: 7.9±1.9 l/min compared to the baseline cardiac output of 4.9±1.3 l/min. Eight weeks after the shunt
procedure, an increase in cardiac output was observed in
comparison not only to the baseline value but also to the
measurements obtained immediately after opening of
the shunt, measuring 9.9±2.7 l/min.
Echocardiography tests revealed a gradual increase in
left ventricular end-diastolic diameter, reaching the
maximal left ventricle dilation at 8 weeks (Fig. 1).
The acute and chronic hemodynamic changes were
demonstrated by pressure-volume loops at baseline,
immediately after the shunt, and after 8 weeks (Fig. 2).
There was an immediate rise in the LVEDV (104±27
ml) compared to the baseline volume (75±26 ml), and
eight weeks later the LVEDV reached 111±22 ml.
Heart catheterization
A dual-micromanometer transducer conductance
catheter (7F, Sentron, The Netherlands) was used to
determine the volume of the ventricle on-line, by measuring the time-varying electrical conductance of the
segments of intraventricular blood [8]. The catheter’s
position along the long axis of the left ventricular cavity
via the left femoral artery was set under fluoroscopic
guidance and verified by inspection of the segmental
conductance signals: a correct position was assumed if
the signals of at least the four most distal segments dis-
Discussion
This study demonstrates that the A-V shunt heart failure model is capable of producing stable, immediate and
long-term high cardiac output (overload) dilation. None
of the eight goats demonstrated clinical signs of pulmonary congestion. Fortunately, these results are in contrast with the high mortality rates (77%) and signs of
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Acute and chronic heart dilation model-induced in goats by carotid jugular A-V shunt
The Swan-Ganz and the conductance catheters that
were used to monitor the heart hemodynamic changes
immediately after the creation of the A-V shunt revealed
interesting results. The abrupt rise in cardiac output
generated huge hemodynamic changes. The LVEDV
increased from 75 ml to 104 ml, while the LVESV reduced from 27 ml to 20 ml, together resulting in an
abrupt rise in left ventricle ejection fraction (from 57%
to 79%) and stroke volume (from 37 ml to 72 ml).
Strangely, no changes in heart rate were observed. We
observed a moderate rise in the dPdt max (from 1361
mmHg/s to 1423 mmHg/s), as well as a significant rise
in peak ejection rate (PER) from 280 (ml/s) before the
shunt to 446 (ml/s) immediately afterward. All these
dramatic changes were reversible at this point in time,
by closure of the shunt. These results suggest that the
wide changes in left ventricle model are within the efficient part on Starling’s curve.
Another advantage of the shunt model is that it is possible to evaluate the patency of the shunt by palpating
the blood thrill in the neck. The shunt’s location facilitates access to ultrasonic measures for a more precise
evaluation, as well as temporary closure, obtained by
applying manual pressure at the animal’s neck.
Our study ended 8 weeks after the creation of the A-V
shunt, leaving unanswered the question of possible heart
failure development in this model after a longer follow
up period.
In conclusion, the carotid jugular A-V shunt in goats
causes significant left heart dilation without signs of
heart failure, and is reproducible with low animal mortality.
Figure 1. Left ventricular end-diastolic volume assessed
by echo cardiography at 2-4 weeks intervals.
Address correspondence to:
Dr Ir FH van der Veen, Cardiothoracic Surgery, PO
Box 5800, 6202 AZ, Academic Hospital, Maastricht,
Netherlands, Email [email protected].
Figure 2. Pressure volume loops before I, 45 minutes
after II, and 8 weeks after the creation of the
shunt.
References
pulmonary congestion that commonly occur within 24
hours of performing the A-V shunt in small animals, as
reported by Flaim and coworkers [10]. This discrepancy
is probably due to the relatively small A-V shunt of approximately 10mm, used in our study (in goats weighing 51 to 80 kg). Moreover, in the present study the
animals presented neither clinical nor hemodynamic
signs of heart failure, such as tachycardia or an increase
in LVEDP, as was observed with inferior vena cava
aortic A-V shunt applied in mongrel dogs [7]. The successful compensatory mechanism in the goat carotid
jugular A-V shunt is the reason for the lack of signs of
renal failure such as were demonstrated in a rat aortovenocaval fistula by Wegner and coworkers [12]. Therefore, the described model should be considered a compensatory overload dilation model rather than a heart
failure model.
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