24 CAFFEIN IN NEPHBECTOMIZED RABBITS. 



May 9: 3 p. m., double nephrectomy; 4.30 p. m., 10 cc of 2 per cent caffein injected 

 subcutaneously. 



May 10: 9 a. m., condition good; no symptoms; 10.30 a. m., 2 cc of blood drawn 

 from ear;* 12 m., 15 cc of 2 per cent caffein injected subcutaneously; 5 p.m., no 

 symptoms, but reflexes slightly increased. 



May 11: 9 a. m., condition good, but slight increase of reflexes present; 2.10 p. m., 

 weight, 1,755 grams; 9 cc of 2 per cent caffein injected subcutaneously. 



May 12: 4.30 p. m., rabbit alive, reflexes increased, but no other symptoms, standing 

 in cage, general condition good. 



May 13: 9 a. m., found dead. 



Rabbit 805. ~ White female; weight, 2,241 grams. 



May 9: 3.50 p. m., double nephrectomy; 4.33 p. m., 11 cc of 2 per cent caffein 

 injected subcutaneously; 5.30 p. m., no symptoms. 



May 10: Condition good, no symptoms; 10.30 a. m., 2 cc of blood drawn from ear 

 vein; 12 m., 15 cc (?) of 2 per cent caffein injected subcutaneously; 5.30 p. m., no 

 symptoms. 



May 11: 9 a. m., found dead; warm; abdomen swollen; rabbit apparently had 

 diarrhea. 



The experiment on rabbit No. 803 fully corroborates the results 

 obtained in the previous series, the rabbit having survived a total 

 amount of 0.68 gram of caffein, or approximately 0.4 gram per kilo. 

 Although the history of rabbit No. 805 might seem to suggest cumu- 

 lative effect, closer analysis shows that this is improbable. After the 

 first dose no effect was observed nor were any symptoms present at any 

 time for about 5J hours after the administration of the second dose 

 of caffein. Death in this case was therefore not due to caffein, but 

 was in all probability the result of the operation. Rabbit No. 804 

 survived a total dose of 250 mg per kilo and lived at least 2J hours 

 after an additional injection of 100 mg caffein per kilo was made. 

 Since a dose of 250 mg per kilo was found to be fatal in most cases 

 when injected subcutaneously into normal rabbits, there can be no 

 doubt of the absence of cumulation of the drug in this case also. 

 This may be accounted for by the increased rate of elimination into 

 the stomach and intestines which takes place when the kidneys are 

 removed by increased oxidation, or it may be due to the formation of 

 substances antagonistic to caffein. That the increased excretion of 

 caffein through the walls of the stomach and intestines is not the 

 cause of the absence of cumulation is evident, for, as pointed out 

 before, reabsorption takes place. 



It is hardly conceivable that oxidation in the tissues should be 

 affected. According to Von Noorden 28 purin metabolism is not influ- 

 enced in chronic renal diseases, while protein catabolism seems to be 

 decreased. The formation of substances antagonistic to caffein is 

 therefore highly probable. No evidence of their presence, however, 

 could be obtained by the methods thus far employed in the present 

 investigation. The following experiments were carried out to test 

 this suggestion: 



For special purposes. 



