754 
PHARMACOLOGY 
DISCUSSION 
Chairman Cohen : Dr. Levy, if you had your 
choice, as you do in many cases, to pick out one 
preparation that you felt was most likely to 
give you some meaningful answers in terms of 
the pharmacology of a new agent, would you 
use your isolated atrial muscle, papillary mus- 
cle, or an intact preparation? 
Dr. Levy : Basically as an in vitro pharmacol- 
ogist, if I can use that phrase, I would choose 
the rabbit left atrium and the cat papillary as 
the most representative. I think we would cover 
most of the area using those two preparations. 
Of course, as I showed on the earlier slide, one 
often may be surprised, despite what you see on 
these isolated preparations, when one puts the 
same material into the intact animal or in man. 
I would like to think that the earlier the new sub- 
stance can be tried in man, the less likely it is 
that we are going to get into trouble and deal 
with false positives. But I prefer the rabbit left 
atrium and the cat papillary as major predictors 
of myocardial effects. 
Sidney Cassin, University of Florida, 
Gains ville: I'm just curious about the relation- 
ship and the choice of agonist and antagonist 
that you use. I'm curious whether you would 
comment about an interaction between aldos- 
terone, propranolol and ouabain? Do you use 
these in agonist-antagonist experiments? 
Dr. Levy: In this particular case we were 
testing the question, "Does aldosterone antag- 
onize the cardiotonic effect of ouabain?" That 
was one question being tested. If you pre- 
treated the human or rabbit atrium with the 
mineralo-corticoid, then challenged with the 
glycoside, you did not block the normal ino- 
tropic response. 
Dr. Cassin : What reason did you have to be- 
lieve that you might get a response? 
Dr. Levy: In antagonism? 
Dr. Cassin : Yes. 
Dr. Levy: According to the Wilbrandt hy- 
pothesis, the mineralo-corticoid was a competi- 
tive antagonist of ouabain at the membrane 
level in terms of sodium transport. This was a 
very early hypothesis that was tested on red 
blood cells. In that particular system, in terms 
of ionic transport, there was a competition. Yet 
on the contractile system of the atrium of the 
rabbit and on the human, there was no antago- 
nism. 
Dr. Cassin : And the propranolol. . . . 
Dr. Levy: And similarly, with proprano- 
lol. We tested whether the inotropic effect of 
ouabain was mediated through a catecholamine 
mechanism or a beta adrenergic mechanism by 
using it on the rabbit atrium. We first gave the 
antagonist, then gave the glycoside, which pro- 
duced a normal effect. When we tested it on 
the human atrium, propranolol was found not 
to antagonize the cardiotonic effect of the gly- 
coside. 
