624 
PHYSIOLOGY 
of stresses much better. It's interesting. I didn't 
know about the sympathetic innervation. 
E. Lepeschkin, University of Vermont, 
Burlington, Vermont: Hov^ was hypoxia pro- 
duced? Was it in a nitrogen saturated atmos- 
phere or was the profusion discontinued? 
Dr. Kent: The gas for the control studies 
was 95% oxygen and 5% COo. We maintained 
the hypoxia studies at 5% oxygen, 5% COo, and 
the balance was nitrogen. There was only low- 
ered oxygen tension. 
M. N. Levy, Mt. Sinai Hospital, Cleveland, 
Ohio: Carrier, Barger, et al, and Buccino and 
Friedman have described a very pronounced 
positive inotropic effect on the ventricular my- 
ocardium with acetylcholine in animals in 
which the myocardial catecholamines have been 
depleted with reserpine, or have been treated 
with beta blocking agents. Have you seen any- 
thing of that sort in your preparations, either 
in the normal or in the denervated preparation? 
Do you think that might represent a response 
that's at a completely different dose level ? 
Dr. Kent: The work of Friedman that you 
quoted was in the papillary muscle. We have not 
actually carried out those experiments in the 
denervated papillary muscles. They were work- 
ing at room temperature with slowly beating 
papillary muscles, and it could be just a differ- 
ence in temperature and a difference in rates. In 
one of the earlier slides, we saw a small positive 
response to acetylcholine. I'm not sure why the 
difference exists, except that the experimental 
conditions were quite different. We've also seen 
a late positive inotropic response when we 
blocked the ability of the heart to release nor- 
epinephrine with cocaine, for example. Cocaine 
treatment of the normal heart will block its re- 
lease of norepinephrine. So, with high doses of 
acetylcholine in a cocainized preparation, we 
get no early response, but then we get a re- 
sponse several minutes later. I am not sure of 
the exact mechanism of that. So, I don't think 
it's necessarily as simple as we've described 
here. 
J. V. Levy, Presbyterian Hospital, San Fran- 
cisco, California: With regard to rate depend- 
ency, in isolated preparations, is there any dif- 
ference in the force frequency relationship 
between the normal and the denervated prepara- 
tion? 
Dr. Kent : No. That's been carefully studied 
now, and there is no difference. The only re- 
quirement is that the force frequency relation- 
ship be carried out with a threshold voltage of 
stimulation because a higher voltage causes nor- 
epinephrine release from the normal muscles. 
There will then be a difference then because the 
chronically denervated preparation won't per- 
form as well as the normal. 
J. P. Ellison, Tulane University, New Orle- 
ans, Louisiana: Firstly, since you use eventu- 
ally an isolated preparation, I wouldn't see any 
profound objection to attempting the sympa- 
thetic denervation with 6-hydroxydopamine 
rather than direct neuralization. Have you com- 
pared this ? 
Dr. Kent: We have not. That's certainly an 
interesting tool that deserves much more study. 
Dr. Ellison: The second point is that this 
residual population of postganglionic parasym- 
pathetic ganglion cells that you have, is, I be- 
lieve, initially responsive both to cholinergic 
and adrenergic preterminals, and I wonder if 
this population is viable? I suppose it is, and I 
wonder how its responses might influence your 
results ? 
Dr. Kent: The postganglionic cholinergic 
fibers can be stimulated. In the interactions 
we've thus far looked at, I oan't see any pos- 
sibility of their influencing our results. 
