TOXICITY OF CAFKEIN IN NEPHRECTOMIZED RABBITS. 25 



TEST FOR THE PRESENCE OP SUBSTANCES ANTAGONISTIC TO CAPPEIN (SERIES 



IV AND V). 



Rabbits Nos. 800 and 801 received 0.3 gram per kilo a short time 

 after the removal of both kidneys; the same dose was repeated on 

 rabbits Nos. 815 and 816 about 24 hours after nephrectomy. The 

 results are as follows: 



SERIES IV, GROUP A. Caffein administered within a few hours after operation. 



Rabbit 801. Gray female; weight, 1,385 grams. 



May 6: 11.30 a. m., double nephrectomy; 3.52 p. m., condition good; 21 cc of 2 

 per cent caffein injected subcutaneously; 3.58 p. m., mild convulsion reported; 

 5 p. m., convulsion and death. 



Rabbit 800. Gray male; weight, 1,620 grams. 



May 6: 11.50 a. m., double nephrectomy; 3.50 p. m., 25 cc of 2 per cent caffein 

 injected subcutaneously (in several places); 4 p. m., rabbit looked sick, twitching of 

 muscles of face and neck, anterior extremities paralyzed, respiration deeper and less 

 frequent than usual and somewhat difficult; 4.30 p. m., died; no convulsions had 

 been observed, although under constant observation. 



SERIES IV, GROUP B. Caffein administered on the day after operation. 



Rabbit 815. Belgian hare, male; weight, 1,755 grams. 



May 21: 3.15 p. m., double nephrectomy by lumbar incision, loss of blood slight, 

 condition after operation good. 



May 22: 10 a. m., paralysis of anterior extremities; 10.20 a. m., temperature 101.2 

 F., weight 1,635 grams; 10.55 a. m., 25 cc of 2 per cent caffein injected subcutane- 

 ously; 11.30 a. m., slight increase of reflexes, no other symptoms; 12.20 p. m., reflexes 

 markedly increased, breathing also abnormally increased; 1.30 p. m., rabbit lying on 

 its side, struggled occasionally, in a comatose condition, dyspnoea quite marked; 

 1.35 p. m., died. 



Rabbit 816. Belgian hare, male; weight, 1,765 grams. 



May 21: 3.35 p. m., double nephrectomy, loss of blood slight, condition good after 

 operation. 



May 22: 10.15 a. m., temperature 101 F., weight 1,745 grams; 10.50 a. m., 25 

 cc of 2 per cent caffein injected subcutaneously; 11.30 a. m., reflexes markedly in- 

 creased; 12.20 p. m., symptoms of caffein poisoning pronounced, rabbit very hyper- 

 sensitive, responded with a tremor when touched, respiration increased in rate and 

 depth; 1.30 p. m., rabbit hypersensitive, attitude normal; 2.15 p. m., paralysis of 

 extremities, dyspnoaa, increased sensitiveness; 5 p. m., condition unchanged. 



May 3: 9 a. m., found dead; cold and stiff. 



Analysis of the results obtained in these two groups of experiments 

 tends to show a somewhat decreased toxicity of caffein when given 

 some time after the removal of the kidneys. Although rabbits Nos. 

 815 and 816 did not survive the effect of a large dose of caffein, 

 it is nevertheless obvious that the resistance was greater than in 

 rabbits Nos. 800 and 801, both of which died soon after caffein was 

 injected. They seemed to be overwhelmed with the effect of the 

 drug. In rabbit No. 800 paralysis set in without the development 

 of convulsions. 



Thus only a depressing effect followed the injection of a dose which 

 in the normal rabbit is usually fatal, with the production of convul- 



