TOXICITY OF CAFFEIN IN NEPHRECTOMIZED RABBITS. 27 



May 23: 9 a. m., condition good; 10 a. m., weight 1,845 grams, 19 cc of 2 per cent 

 caffein injected subcutaneously; 11 a. m., reflexes increased, very sensitive; 5.15 

 p. m., rabbit standing in cage, reflexes increased, condition otherwise good; observed 

 frequently all day, no paralysis or convulsions occurred. 



May 24: 8.15 a. m., rabbit standing in cage, still hypersensitive, condition otherwise 

 good; 4.30 p. m., rabbit still alive, standing in cage, reflexes increased, but no con- 

 vulsions noticed; observations made several times during the day. 



May 25: 8.50 a. m., rabbit alive, in good condition, still hypersensitive, but somewhat 

 less so than day before; died about 11 a. m. 



Lived 49 hours after caffein injection, or 70 hours after double nephrectomy. 



Rabbit 819. Yellow male. 



May 22: 11 a. m., weight, 1,765 grams; 1.30 p. m., double nephrectomy. 



May 23: 9 a. m., condition good; 10 a. m., weight 1,725 grams, 17.25 cc of 2 per cent 

 caffein solution injected subcutaneously; 11 a. m., hypersensitive, reflexes very 

 much increased, observed at frequent intervals all day; 5.15 p. m., condition about 

 the same as at 11 a. m., rabbit standing in the cage, no paralysis. 



May 24: 8.15 a. m., rabbit found dead; stiff and cold. 



Lived more than 18 hours after caffein injection and between 28 and 46 hours after 

 double nephrectomy. 



Rabbit 821 .Black male; weight, 1,850 grams. 



May 22: 2.10 p. m., double nephrectomy. 



May 23: 9 a. m., condition good; 10 a. m., weight 1,815 grams, 18.5 cc of 2 per cent 

 caffein injected subcutaneously; 11 a. m., reflexes exaggerated, rabbit hypersensi- 

 tive, observed at frequent intervals, no paralysis or convulsions; 5.15 p. m., still very 

 sensitive, condition as at 11 a. m. 



May 24: 8.15 a. m., rabbit found dead; stiff and cold. 



The results of these six experiments show that absorption of caffein 

 was quite rapid, symptoms of caffein intoxication appearing within 

 from 45 to 60 minutes after its injection, but they were much more 

 marked in the rabbits of group B (819, 820, and 821) than in those 

 of group A (788, 789, and 790). This suggests a diminished toler- 

 ance for the drug with the lapse of time after nephrectomy, but the 

 duration of life in group B after the administration of caffein does 

 not indicate such a condition. It will be noticed that one rabbit in 

 each group lived 2 days after receiving caffein, while two other 

 members of each group died in the night following the adminis- 

 tration of the drug. Moreover, the result of anaesthesia in rabbits 

 Nos. 788, 789, and 790 should not be left out of account. It is 

 conceivable that at the time caffein was injected into these rabbits 

 from two to three hours after the operation, enough ether remained 

 in the tissues to antagonize, to some extent at least, the stimulating 

 effect of caffein. This seems to contradict the results of the experi- 

 ments with large doses of caffein in rabbits 800 and 801. It is sig- 

 nificant, however, that symptoms of excitement were absent in one 

 rabbit and were not especially marked in the other, thus pointing 

 to the antagonistic effect of ether. Symptoms of nervous disturbance 

 may therefore be suppressed when larger amounts of caffein are given 

 shortly after the removal of the kidney before the effects of anaes- 

 thesia have passed off. The increased toxicity of caffein under these 



