CHRONIC INTOXICATION DOGS. 85 



may seem to contradict the results of experiments on dogs 11 and 20, in which larger 

 doses of caffein failed to induce symptoms of intoxication. But it should be observed 

 that the diet, which consisted almost exclusively of carbohydrates, was given only 

 during the administration of caffein, while in the experiments of series B the sub- 

 jects received a low protein diet for several weeks before the administration of caffein 

 was begun, and it was continued through the entire caffein period. It will be re- 

 marked that the absence of cumulative action in the experiments of the preceding 

 series was also observed in dogs on high as well as on low protein diet. The appearance 

 of symptoms after smaller doses of caffein in the latter experiments might suggest 

 cumulative action, but since these symptoms disappeared on continued administration 

 of the substance cumulation is clearly not indicated. The gastrointestinal lesions 

 observed on post-mortem examination were, it will be recalled, also found in rabbits 

 similarly treated. The explanation suggested probably applies also in the case of 

 dogs. 



SERIES C. 



As already pointed out in the experiments on acute toxicity of caffein, young growing 

 dogs are probably more resistant to caffein than adults. That this may also hold true 

 in chronic caffein intoxication seemed indicated by the following experiments. 

 Dog 33. Black female puppy. Weight, 4 kilos. Had been continuously on a meat 



diet. 



December 22: 2.30 p. m., received 0.69 gram of caffein (0.172 gram per kilo); 3.15 

 p. m., no symptoms except that feces were fetid. 



December 23: 11.30 a. m., received 0.79 gram of caffein (0.197 gram per kilo); 1.30 

 p. m., no symptoms. 



December 24: 11 a. m., received 0.87 gram of caffein (0.2009 gram per kilo); 4 p. m., 

 no symptoms. 



It will be observed that the only effect produced in dog 33 by feeding caffein was 

 increased intestinal putrefaction, although 2.37 grams of caffein were given in three 

 days. Additional data on the effects of the age of animals on the resistance to caffein 

 seemed_desirable. The following experiments were therefore carried out. Six puppies 

 of the same litter were weaned when 7 to 8 weeks old and put on a milk diet. Three 

 of them received this diet throughout the experimental period. Meat was substituted 

 in the other three a few days before the administration of caffein was begun, and was 

 continued until the end of the experiment. Caffein was given by mouth; the initial 

 dose, which was administered for several days and then gradually increased, being 

 160 to 200 mg for each dog, except one, which received only 100 mg per kilo for several 

 days and then an increased amount. 



