LAWRENCE S. COHEN, GEORGE F. VASTAGH AND JERE H. MITCHELL 
713 
PACED LEFT VENTRICULAR dp/dt RESPONSE 
100 
90 - 
80 - 
70 - 
60 
PER CENT 
CHANGE 
FROM 50 
CONTROL 
40 
30 
20 
10 
-• ALPRENOLOL (A) 
-O PROPRANOLOL ( P) 
-A AY 21011 (AY) 
-A MJ 1999 (S) 
* P 
** P 
■0.05 
= 0.01 
3.125% 6.25% 12.5% 25% 50% (00% 
% OF BLOCKING DOSE 
(A) 0.0015 0.003 0.006 0.012 0.024 0.048 
(P) 0.003 0.006 0.012 0.024 0.048 0.096 
(AY) 0.00625 0.0125 0.025 0.05 0.1 0.2 
(S) 0.025 0.05 0.1 0.2 0.4 0.8 
mg/kg, i.v. 
gram to milligram doses of two drugs, and as- 
sume that they are of equal potency because 
they are the same milligram dosage. It is for 
that reason that we determined, for each of the 
four agents used, what was 100% blockade, 
and we defined that as a lack of response to an 
isoproterenol challenge. Now for one drug, 
just to give you figures, that dose might be 1 
mg. For another drug, it might be 10 mg. We 
would consider them as being of equal potency, 
and that is 100% blockade by our criterion. At 
that point we use serial dilutions downwards. 
And so we did not use the same dose of drugs 
at each stage of the experimental design but we 
did use the same per cent of total blocking 
ability. I think in terms of our own study, this 
may answer some of the questions about "po- 
tency of different agents." Potency in and of 
itself really does not mean very much. It is 
pharmacologic potency that one wants to deal 
with. 
Dr. Somani : The second comment I had was 
in relation to the mechanism of anti-anginal 
Figure 5. — During cardiac pacing the intrinsic effects 
of beta blockade upon left ventricular dp/dt. All four 
agents lowered intrinsic left ventricular dp/dt 
equivalently. 
feots of these agents may prove to be signif- 
icant in the treatment of patients vdth an- 
gina pectoris. 
DISCUSSION 
PiTAMBAR Somani, Abbott Laboratories 
North Chicago: This was a very elegant study 
demonstrating the differences between various 
beta blockers. Some of the data that you have 
shown is at some variance with what other 
investigators have reported regarding the po- 
tency of practolol, because practolol in isolated 
systems, as well as in the whole animal is about 
%oth as potent as propranolol in the same mil- 
ligram dose. I was wondering if you would 
care to comment on this ? 
Dr. Cohen: That is an excellent question, 
and one to which we address ourselves in the 
experimental design of the study. It became 
quite clear that one really cannot look at milli- 
PACED left VENTRICULAR dp/dt RESPONSE 
TO ISOPROTERENOL CHALLENGE 
PER CENT 
CHANGE 
FROM 
CONTROL 
• ALPRENOLOL (A) 
O PROPRANOLOL ( P) 
A AY 21011 (AY) 
■A MJ 1999 (S) 
* P 
** P 
^0.05 
= 0.01 
3.125% 6.25% 12.5% 25% 50% 100% 
% OF BLOCKING DOSE 
(A) 0.0015 0.003 0.006 0.012 0.024 0,048 
(P) 0.003 0.006 0.012 0.024 0.048 0.096 
(AY) 0.00625 0.0125 0.025 0.05 0.1 0.2 
(S) 0.025 0.05 0.1 0.2 0.4 0.8 
mg/kg, i.v. 
Figure 6. — Left ventricular dp/dt response to an iso- 
proterenol challenge during cardiac pacing. AY210- 
ll>Propranolol>Sotalol = Alprenolol blocked the ino- 
tropic response to isoproterenol in that order. 
