28 CAFFEIN IN NEPHRECTOMIZED RABBITS. 



conditions that is, when administered a few hours after nephrec- 

 tomy is in all probability due to its effect on the heart. Ether and 

 caffein, when given in large amounts, are thus antagonistic where the 

 nervous system is concerned and synergistic with respect to cardiac 

 action. 



Again, it should be observed that the duration of life after the 

 injection of 0.2 gram caffein per kilo was the same whether caffein 

 was administered from two to three hours after removal of the 

 kidneys or whether it was administered the next day. The increased 

 osmotic pressure at this time should make absorption more rapid 

 and therefore the toxicity greater, while the antagonistic effect of 

 ether when caffein is given after the operation should diminish the 

 toxicity, but the fact that such was not the case justifies the con- 

 clusion that some mechanism which neutralizes the toxicity of 

 caffein was present. Moreover, some experiments with smaller doses 

 show that the resistance to caffein is greater after removal of the 

 kidneys. It was shown in Bulletin 148 that for some rabbits 100 mg 

 of caffein per kilo proved fatal by subcutaneous injection. Such a 

 dose, however, failed in the great majority of instances to produce 

 any symptoms in nephrectomized rabbits. This may be seen by 

 referring to the protocols of experiments on rabbits Nos. 797, 798, 

 799, 803 and 804, (p. 23), and is also shown in the following ex- 

 periments : 



FURTHER TESTS, WITH MEDIUM DOSES, FOR THE TOXICITY OF CAFFEIN (SERIES VI). 



Rabbit 794. Gray female; weight, 1,440 grams. 



May 1: 12.23 p. m., double nephrectomy, an overdose of ether caused suspension 

 of respiration, rabbit was revived by artificial respiration and operation was con- 

 tinued, loss of blood about 1 cc; 3.38 p. m., 8 cc of 2 per cent caffein injected sub- 

 cutaneously; 5.30 p. m., reflexes increased, hypersensitive, avoided light. 



May 2: 9 a. m., reflexes increased, but less than day before, still avoided light, 

 otherwise condition good, feces normal; 1 p. m., rabbit found dead, still warm and 

 rigor mortis present. 



Lived about 21 hours after the injection of caffein. 



Rabbit 795. Gray female; weight, 1,375 grams. 



May 1: 11.52 a. m., double nephrectomy, ether narcosis, operation about 18 minutes, 

 uneventful, estimated loss of blood about 1 cc; 3.35 p. m., condition good, 8 cc of 2 

 per cent caffein injected subcutaneously; 5.30 p. m., condition good, no symptoms. 



May 2: 9a.m., condition of rabbit good, feces soft; 10 p. m., rabbit looked comatose, 

 paralyzed. 



May 3: 9 a. m., found dead. 



Lived more than 30 hours after injection of caffein. 



Rabbit 796. Gray female; weight, 1,460 grams. 



May 1: 12.50 p. m., ether narcosis, double nephrectomy, loss of blood slight, about 

 1 cc, operation uneventful; 3.35 p. m., condition good, 8 cc of 2 per cent caffein 

 injected subcutaneously; 5.30 p. m.. rabbit paralyzed, feces soft. 



May 2: 9.30 a. m., paralysis more marked than day before, feces soft; 2.25 p. m., 

 was bled to death. 



Lived 23 hours after injection of caffein. 



