ACUTE INTOXICATION GUINEA PIGS. 45 



Guinea pig 7t. Brown and white male. Weight, 560 grams. Diet. oats. 



October 7: 3 p. m., 6.5 cc 2 per cent caffein (0.232 gram per kilo) aaueous solution 

 administered bv subcutaneous injection; 3.35 p. m., reflexes increased. 



October 10: found dead. Autopsy: NOB. 70, 71, 72 showed congestion of organs. 



The reaction to caffein in the experiments of this series (C) showed considerable 

 variation. The appearance of symptoms, as well as the final outcome of the experi- 

 ments, differed markedly in a number of cases, notwithstanding the fact that the 

 conditions were the same; thus the administration of 0.2 gram per kilo to guinea 

 pigs, all of which received the same diet, induced no symptoms in two of the animals 

 (Nos. 66 and 65), while marked symptoms were observed in the other four; in two 

 of these the symptoms appeared in one hour and a quarter after injection, and in two 

 others (Nos. 68 and 69), mild symptoms only appeared in 20 or 25 minutes. The 

 last two were under observation for 4 hours longer, but there was no visible change 

 in their condition. The duration of life in all of these guinea pigs, as indicated in 

 the table, likewise varied. Two (Nos. 60 and 68) died during the night after they 

 received caffein, one survived (No. 65), and three others (Nos. 57, 66, and 69) lived 

 2, 5, and 9 days, respectively. Experiments with larger doses likewise showed 

 differences in the behavior of these animals toward caffein, but they were not quite 

 so marked. As shown in the table, symptoms appeared in from 35 minutes to 1 .5 hours 

 after injection. The duration of life was less than 1 day in two pigs, about twice as 

 long in two others, and in one case between 2 and 3 days. 



A comparison made with results obtained in the preceding series shows a striking 

 difference in the resistance to caffein. As 2 decigrams per kilo proved more rapidly 

 fatal to the guinea pig than the larger doses employed in the later experiments, this 

 difference in the resistance to caffein may be due to several factors. As pointed out 

 in the experiments on rabbits, age might be an important factor influencing the 

 toxicity of caffein. Unfortunately, no accurate data were available on the age of the 

 guinea pigs, but they were all apparently full grown, although they differed in weight 

 considerably. The difference in their ages was in all probability not very great. 

 Moreover, it will be observed that the resistance in series B and C differed in animals 

 of approximately the same weight. This is evident on comparing experiments Nos. 

 20, 38, and 13 of series B with Nos. 65, 66, and 69 of the next series. Again, further 

 inspection and analysis of these tables show no difference in the toxicity, although 

 there may be considerable difference in the weight, from which it may be concluded 

 that the animals were of about the same age or that this plays no part in the resistance 

 to caffein in the guinea pig. 



Diet is another factor which should be taken into consideration in this connection. 

 The recent work of Hunt 39 indicates that this may influence the resistance of animals 

 to some poisons. Our experiments, however, fail to show any difference in the toxicity 

 of the caffein in guinea pigs, whether fed oats, carrots, or both, for different results were 

 obtained on the same diet, and there seemed to be little or no difference in the toxicity 

 of caffein when the diet was different. Other explanations suggest themselves to 

 account for the results obtained. Seasonal changes have been assigned by a number 

 of investigators as a cause of variation in the resistance to drugs. According to Focke, 24 

 frogs are more susceptible to digitalis in the spring than in the summer, while Mosch- 

 kowitsch 61 and Edmunds 21 reported the very opposite results. Schmiedeberg's M 

 observations on strophantin in frogs were in harmony with those of Edmunds 21 and 

 Moschkowitsch. 61 Similar results were reported with guinea pigs. Harrington's 34 

 experiments indicate that stimulation of the vagus is less effective from October to 

 January than from February to April, when they are also much more susceptible to 

 operative po>cedure. Hunt found that the resistance of guinea pigs to aceto nitril is 

 about twice as great in the summer months as it is in January and February. 



Race might also be thought of as an important factor in this connection. Since the 

 guinea pigs used at different seasons of the year were of several varieties, there is no 



