p. KEZDI, S. N. MISRA, R. K. KORDENAT AND T. J. SMITH 
71 
ing the development of cardiogenic shock. First, 
isoproterenol was given for about two hours 
following which no medication was given for one- 
half to one hour and then isoproterenol and nor- 
epinephrine were combined. Figures 12 and 13 
show the results of these studies. Following ad- 
ministration of 2-4 /xg/min of isoproterenol, 
there was a significant increase in heart rate 
and slight further decrease of mean blood pres- 
sure. Peripheral resistence also decreased 
while cardiac output slightly increased. Left 
ventricular dP/dt max significantly increased. 
Tachyarrhythmias and periods of ventricular 
tachycardia occurred during isoproterenol ad- 
ministration. 
The combination of isoproterenol at 1 |U.g/min 
with 2-4 /xg norepinephrine resulted in signif- 
icant hemodynamic improvement. There was a 
significant increase in cardiac output and stroke 
volume. Left ventricular dP/dt increased more 
than with isoproterenol alone. Left ventricular 
stroke work increased while left ventricular 
end-diastolic pressure slightly decreased. Pe- 
ripheral resistence showed a decrease with 
small decrease of the mean systemic pressure. 
When myocardial metabolism and left ven- 
Isoproterenol - Alone and in 
Combination with Norepinephrine 
(10 Dogs) BASELINE 
^■SHOCK 
I I ISOPROTERENOL 
VaiSO & NE 
(beats/min) (mmHg) (L/min) (ml /beat) 
Figure 12. — Same as in Figure 8 for isoproterenol and 
for isoproterenol and norepinephrine combined. Sta- 
tistical significance is calculated between shock state 
and treatment with isoproterenol alone and in combi- 
nation with norepinephrine (not between isoproter- 
enol and isoproterenol plus norepinephrine). 
Isoproterenol - Alone and in 
Combination with Norepinephrine 
(10 Dogs) ™ SHOCK 
PR LVEDP LVSW LVdP/dt 
'dynes /sec/cm'^j (mmHg) fg-m) (mmHg/sec) 
Figure 13. — Same as in Figures 9 and 12 for isoproter- 
enol and in combination with norepinephrine. 
tricular end-diastolic and end-systolic volume 
were studied, it was found that isoproterenol 
alone increased excess lactate production and in- 
creased myocardial oxygen consumption (Fig- 
ures 14 and 15). There was no significant 
decrease of the heart volumes with isoproterenol. 
On the other hand, a combination of isoproter- 
enol with norepinephrine led to improvement of 
myocardial metabolism with decrease of my- 
ocardial excess lactate production, an increase 
of the ejection fraction as a result of greater de- 
crease of end-systolic than end-diastolic volume. 
This reversal of myocardial anerobic metabo- 
lism occurred while left ventricular stroke work 
increased indicating a more eflficient oxygen uti- 
lization with the combined treatment. Reversal 
of myocardial lactate production to lactate utili- 
zation occurred only with this combined treat- 
ment. 
The drug studies indicated that the best he- 
modynamic results and metabolic improvement 
in experimental cardiogenic shock were ob- 
tained with a combination of isoproterenol and 
norepinephrine. This occurred when both were 
given at about one-half of the necessary dose to 
produce hemodynamic changes than when given 
alone. This probably was due to an additive ef- 
fect requiring smaller doses of each drug in 
combination to exert maximum improvement. 
