DOSAGE OF THE MAMMALIAN HEART BY CHLOROFORM 81 
A second point of interest is the following. During the continuance of a 
prolonged administration to the heart of a weak or moderately strong CHC1 3 solution, 
the heart seems to become gradually less and less susceptible to the dose that is being 
employed. A kind of temporary and partial immunity seems to become established. 
This is exemplified by many of our tracings. We append pieces from two such 
tracings, Hearts 24 and 26 (Figs. 4 and 5). The apparent wearing off of the effect 
is not due to any real decrease in the strength of the solution. The same solution, 
that at end of a prolonged administration was not depressing the cardiac activity 
so potently as it had done at the outset of the observation, on being, after a brief 
pause, readmitted to the heart, immediately acted as potently as at outset once 
more. We have been accustomed to denote this for convenience in the laboratory 
as 'immunity;" but the relative insusceptibility thus attained was very short 
lasting. 
Excitatory Action of Chloroform 
Especially with stronger solutions of the drug, it was usual for the first effect 
of the administration to be a distinct though slight increase in amplitude of both auri- 
cular and ventricular contractions. The fact that strong solutions left as an after effect 
on the ventricle a condition of inco-ordinate fibrillar convulsion likewise suggests an 
irritative excitatory effect of such doses of the drug. 
After cessation of the administration of the drug in moderate dose it was not 
unusual for the recovery of the beat to pass over for a short time into a condition of 
super-activity. Many of our tracings illustrate this. We were at first inclined to 
attribute this to some slight asphyxia of the cardiac tissue. Control observations 
with boiled-out modified Ringer's solution, administered under nitrogen pressure, 
showed, however, that the after effect of the CHC1, solution cannot be clearly and 
simply explained by asphyxia. Moreover, our CHC1 3 solutions were as oxygenated 
and delivered under the same oxygen pressure as were our chloroform-free solutions. 
It may, however, be that under the action of the chloroform the tissue allows an 
accumulation of waste products that it excretes freely in its unchloroformed condition, 
and that these effete decomposition products make an excitatory effect which they can 
exert on the tissue patent after disappearance of the chloroform depression. 
A similar condition might explain the gradual reduction in the depressant 
effect of a constantly-maintained strength of CHC1, solution continuously exhibited 
to the tissue over a period of several minutes duration, e.g., five to twenty minutes. 
This reduction does, as stated and illustrated above, actually occur. 
We have repeatedly noticed that the amount of perfused solution passing 
through the coronary circulation per unit time considerably diminishes soon after the 
CHC1, containing solution has replaced the CHC1 3 free solution. Since the pressure 
and temperature of the solutions supplied was the same in both cases, the diminution 
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