Table II . — Perfusion of the isolated frog's heart with caffeine citrate in Ringer's solution. 
Protocol 13, October 7, 190S. 
Protocol 14, October S, 1908. 
Output 
Output 
Time. Rate. 
I>er 
Time. 
Rate. per 
5 minutes. 
5 minutes. 
C. c. 
; C.C. 
11. 05 24 
la 10 
07 
11.10 24 
18 
10.15 
27 19 
Caffeine citrate ^ per cent. 
10.20 
28 21 
11. 11 26 
10.25 
27 20 ! 
11. 15 20 
10 
laso 
1 27 20 1 
11. 18 0 ' 
1 
Caffeine citrate per cent. 
11.20 
4 
1 10. 32 1 
1 29 1 = 
10.35 1 
1 30 1 22 i 
1 ia40 i 
1 27 i 23 j 
10. 45 
11.05 
1 
Having thus determined the manner in which the frog’s heart 
reacts when perfused with definite percentages of caffeine or acet- 
anilide, a third series of experiments were carried out to determine 
to what extent and in what manner the action of acetanihde in 
solutions of various strengths could be modified by the addition of 
such amounts of caffeine as had been shown to possess a definite 
stimulant action. Two methods of determining these effects were 
employed, one based upon the differences in the time necessary to 
stop the heart, the other upon changes in rate and output. It had 
been shown by a number of experiments, using one-seventh of one per 
cent solutions of acetanihde alone, that the heart was stopped by 
the poisonous action of the drug at the following intervals: 37, 17, 
9, and 30 minutes, or on the average 23.1 minutes after the perfusion 
of the drag was begun. Accordingly one-seventh per cent acetanihde 
solutions to which one two-thousandth per cent caffeine citrate had 
been added were perfused at the same temperature through another 
series using frogs of approximately the same weight. The intervals 
between the introduction of the combined drugs and the stoppage of 
the heart were as foUows: 2.5, 3, 15, and 8 minutes, or on the average 
12.7 minutes after the dmg was started. In both series marked 
irregularities will be noted. Tiffs is probably in great part due to 
the irregularity in the course of acetanihde poisoning and because of ^ 
the great differences in the same series it becomes impossible to draw 
absolute conclusions. The results as they stand, however, incficate 
considerably more toxicity to the heart from the dnigs when exhibited 
in combination than from acetanihde alone. 
The second method of experimenting consisted in poisoiffng the | 
heart with smaher quantities of acetanihde with the idea of keeping ) 
it beating, for some time and then noting the changes in rate and | 
output upon the substitution of the acetanihde caffeine combination. •[ 
These experiments are also somewhat disappointing because of their | 
