17 
failure to show striking modifications in action. It seems possible, 
however, in going carefuUy over the results obtained in this manner 
to point out certain definite changes. In five experiments there was 
clearly a lessened toxicity as a result of using the drugs in combina- 
tion. In fourteen experiments the results were exactly the opposite. 
The rate was lessened in five and in the others there was no change, 
but in all cases there was a decrease in the output over that produced 
by acetanilide alone. Two protocols illustrating this increased 
toxicity are given in Table III. 
Table III . — Perfusion of the isolated frog^s heart with acetanilide, and with acetanilide 
and caffeine citrate in combination. 
Protocol 17, October 10, 1908. 
Protocol 40, October 23, 1908. ' 
1 
1 
Output 
- 
1 Rate. 
Output 
1 Time. 
Rate. 
per 
Time. 
per 
1 
5 minutes. 
1 
5 minutes. ^ 
C. c. 
C. c. \ 
9.50 
29 
9.20 
28 
\ 
9.55 
32 
20 
9.25 
36 
23 
10.00 
32 
25 
9.30 
35 
22 
10.05 
33 
27 
Acetanilide i per cent + caf- 
Acetanilide tV per cent. 
feine citrate 
per cent. 
10. 07 
1 19 1 
9.31 
0 
1 
10.10 
17 
25 
9.32 
Ringer’s solution. 
10.15 
15 
23 
9.35 
26 1 
1 19 
Acetanilide per cent + 
9.40 
33 
19 
per cent caffeine citrate. 
Acetanilide i per cent. 
10.17 
13 1 
9.42 
1 19 
1 
10.20 
14 
26 
9.45 
13 
1 8 
10.25 
11 
27 
Acetanilide ^ per cent + caf- 
10.30 
11 1 
25 
feine citrate ^rrinT per cent. 
Acetanilide Js per cent. 
9. 46 
1 0 
10.32 I 
1 
13 1 
It must be admitted that the changes are not very definite, but as 
in the results obtained by the other method there is some indication 
of increased toxicity from the combination. The results at any rate 
are confirmatory of each other. It may be very clearly stated too 
that there is no lessened toxicity when using the drugs in the above 
strengths and this again substantiates the results shown by the first 
series of experiments. 
In another series of experiments, carried out to determine changes 
in rate and output, smaller amounts of the drugs were used. In these 
such small amounts of the drugs were perfused that the perfusion 
was begun with solutions of acetanilide in Ringer’s solution. The 
second perfusion bottle in addition to the acetanilide contained 
either caffeine citrate or sodium bicarbonate. After a series of read- 
ings using acetanilide had been taken, the combined drugs were per- 
fused and the resulting changes in heart rate and output were noted. 
Acetanilide was used in one-fifteenth per cent strength and caffeine 
citrate in one three-thousandth per cent, and with few exceptions the 
176— Bull. 53—09 2 
