30 CAFFEIN IN NEPHRECTOMIZED RABBITS. 



May 28: 3.15 p. m., ether anaesthesia, kidneys exposed but not removed, wound 

 closed; 4.43 p. m., received 8 cc of 2 per cent caffein (124 mg per kilo) injected sub- 

 cutaneously. 



May 29: 9 a. m., weight 1,250 grams, condition good. 



Under observation until June 10, when weight was 1,345 grams and condition good. 



Rabbit 826. White female; weight, 1,760 grams. 



May 28: 3.30 p. m., kidneys exposed by lumbar incision under ether anaesthesia, but 

 not nephrectomized; 4.42 p. m., 12 cc of 2 per cent caffein (136 mg per kilo) injected 

 subcutaneously . 



Under observation until June 16, when found dead. Rabbit lost 300 grams weight 

 until June 1, after which it began to gain weight slowly. 



Rabbit 824- Belgian hare, female; weight, 1,710 grams. 



May 28: 3.50 p. m., kidneys exposed by lumbar incision under ether anaesthesia; 

 4.40 p. m., 12.5 cc of 2 per cent caffein (146 mg per kilo) injected subcutaneously. 



May 29: paralyzed. 



RESUME AND DISCUSSION. 



A careful study of the preceding experiments shows that in the 

 majority of cases a single dose of from 100 to 150 mg caffein per kilo 

 may be given to a nephrectomized rabbit without producing marked 

 symptoms. Reference to Bulletin 148 shows that 150 mg of caf- 

 fein per kilo were usually toxic, while smaller doses were without 

 effect except in such cases as were associated with some abnormality. 

 These, as may be seen, proved fatal. Doses of 200 mg caffein per kilo 

 were always toxic for the normal rabbit and proved fatal in some 

 but not in all cases. Nephrectomized rabbits likewise manifested 

 symptoms of toxicity when such amounts were administered. The 

 duration of life after injection varied between 18 and 48 hours 

 (approximately). A dose of 200 mg per kilo can not be regarded, 

 therefore, as surely fatal for nephrectomized rabbits, but it is invari- 

 ably toxic. The tolerance for the single dose of this alkaloid is 

 probably a little greater than in the normal rabbit. Furthermore a 

 dose of 150 mg caffein per kilo may produce death when repeated 

 within 24 hours, while smaller doses may be given daily without 

 causing death in nephrectomized rabbits. This is shown in Series 

 III (p. 23), in which the total amount injected, 0.3 to 0.4 gram caffein 

 per kilo, was well borne by rabbits deprived of both kidneys. Larger 

 doses, 0.3 gram caffein per kilo, were also given at a single injection 

 in nephrectomized rabbits. This proved to be rapidly fatal when 

 administered from two to three hours after nephrectomy, while such 

 a dose given about 24 hours after nephrectomy was distinctly less 

 toxic, as the animals lived several hours after receiving caffein. 



The evidence presented in this investigation points strongly, there- 

 fore, to the formation of substances that counteract the effect of 

 caffein when both kidneys have been removed. By the control 

 experiments showing greater toxicity as a result of merely exposing 

 the kidney this contention is greatly reinforced. 



