44 
CARDIAC MODELS 
Hemodynamic changes of mild to moderate 
left ventricular failure also occur quite consist- 
ently, and these consist of a rise in heart rate to 
sinus tachycardia levels, and a rise in left ven- 
tricular end-diastolic pressure (Table II). 
There is a modest decline in cardiac output in 
many animals, but it is not severely depressed. 
Arterial blood pressure is well maintained and 
declines only slightly. 
Table II. — Left Anterior Descending Coronary Artery 
Occlusion in 15 Intact Conscious Dogs (Mean ± SEM) 
Left Ventricular 
Left Ventricular 
Peak Systolic 
Heart 
End-Diastolic 
Cardiac 
Pressure 
Rate 
Pressure 
Output 
(mm Hg) 
(beats/min) 
(mm Hg) 
( L/min) 
Control 
15G±6 
82±5 
6.8±0.8 
3.5±0.3 
Occlusion 
142±7* 
132±9* 
19.2±1.8* 
2.8±0.3* 
* p <0.05, paired differences 
We have carried out extensive studies of the 
natural course of this left ventricular failure in 
dogs follovs^ing acute myocardial infarction, and 
we have also studied the effects of various inter- 
ventions. Improvement in left ventricular per- 
formance is noted in the healing phase one week 
after myocardial infarction, as indicated by re- 
turn of the elevated heart rate and the de- 
pressed cardiac output towards normal, and 
also by improvement of initially depressed ven- 
tricular function curves.^" Elevation of left 
ventricular end-diastolic pressure in the healing 
phase is likely to persist and this has been at- 
tributed to residual left ventricular failure, but 
also to reduced compliance of the infarcted 
ventricle. 
In this preparation various inotropic agents 
have been tested, including digitalis in the form 
of acetyl strophanthidin, glucagon,^^ rapid 
atrial pacing,-" and phentolamine.^i With one 
exception, these interventions were found to im- 
prove ventricular performance at various 
stages after infarction, manifested by a rise in 
cardiac output and lowering of left ventricular 
end-diastolic pressure. However, when acetyl 
strophanthidin is infused in the acute phase of 
infarction, such changes do not occur, and this 
appears to be due to a systemic vasoconstrictor 
effect of digitalis and an attendant increase in 
afterload to contraction (Figure 4). Glucagon, 
on the other hand, typically raises cardiac out- 
put and lowers left ventricular end-diastolic 
pressure in both the acute and healing phases of 
infarction (Figure 5). Similar results are ob- 
tained with phentolamine, an agent which is 
classically known as an alpha-blocking agent, 
but which in addition has inotropic effects. 
Rapid atrial pacing also improves left ventricu- 
lar performance in a similar fashion, implying 
either that the inotropic effect of the rapid rate 
is beneficial to the infarcted ventricle, or that 
the intrinsic heart rate response to infarction is 
inadquate to compensate for the diminished 
stroke volume caused by the ischemic lesion. 
It has also proven possible in this preparation 
to place indwelling coronary sinus catheters 
under fluoroscopy and to study myocardial ener- 
i 
I 
I PRE AS M POST AS 
I 
i 
1 
MEAN 
AORTIC PRESS. 
(mmHg) 
LVEDP 
(mmHg) 
Figure 4. — Hemodynamic effects of infusing 3 
/ug/Kg/min of acetyl strophanthidin in 6 dogs one 
hour (above) and one week (below) after coronary 
occlusion. Above: In the acute phase of infarction 
acetyl strophanthidin caused an increase in aortic 
mean pressure and peripheral vascular resistance, but 
no other significant changes. Below: In the healing 
phase of infarction acetyl strophanthidin caused an 
increase in stroke volume and decline in left ventri- 
cular end-diastolic pressure, evidence of improved 
ventricular performance. The pressor effect was ab- 
sent. Data shown as mean ± SEM. 
*p <0.05, paired differences. 
