LAWRENCE S. COHEN, GEORGE F. VASTAGH AND JERE H. MITCHELL 
711 
LVdp/dt 
mmHg /sec 
Figure 2. — Representative tracing of experimental measurements. Left ventricular dp/dt appears at the top. 
Aortic pressure (AP) and left ventricular pressure (LVP) e^e measured in mm.Hg. Left ventricular diastolic 
pressure is measured in cm.H20. The time is recorded on the abscissa. 
pared with control values was significant only 
at high doses of Sotalol and propranolol. 
The four agents displayed a differing ability 
to block the chronotropic response to an iso- 
proterenol challenge (Figure 4). On the ordi- 
nate, 100% represents the change from control 
heart rate following an isoproterenol challenge. 
The response to isoproterenol following increas- 
ing doses of beta blocker is plotted as a percent 
of the response to isoproterenol prior to beta 
blockade. AY 21011 blocked the chronotropic 
response to isoproterenol most effectively fol- 
lowed by propranolol, aptine and sotalol. 
In a paced preparation, the intrinsic effects 
of beta blockade upon left ventricular dp/dt 
were investigated (Figure 5). All four agents 
lowered intrinsic left ventricular dp/dt equiv- 
alently. 
The left ventricular dp/dt response to an iso- 
proterenol challenge was then looked at (Figure 
6). AY 21011>Propranolol>Sotalol = Alpre- 
nolol blocked the inotropic response to isopro- 
terenol in that order. 
Based on these data it would appear that : 
1. AY 21011 (Practolol) blocked the chrono- 
tropic and inotropic responses to isopro- 
terenol most effectively, followed closely 
by propranolol. 
2. All four agents displayed equivalent in- 
trinsic negative inotropic activity. 
3. Sotalol had the greatest intrinsic negative 
chronotropic effect followed by propra- 
nolol. 
DISCUSSION 
It is difficult to extrapolate these findings 
from the animal laboratory to the clinical sit- 
uation of angina pectoris. It is agreed generally 
that angina pectoris reflects a dynamic state in 
which myocardial oxygen requirements exceed 
myocardial oxygen supply. The major deter- 
