CHRONIC INTOXICATION BABBITS. 63 



CHBONIC CAFFEIN INTOXICATION. 



The object of this study was to ascertain the effect of repeated 

 dosage when caffein was given daily or at longer intervals. The 

 experiments were tried on rabbits and on dogs. As in the experi- 

 ments on acute intoxication, the .animals were under observation for 

 some tune in the laboratory before the administration of caffein 

 was begun in order to ascertain the presence or absence of abnor- 

 mality. The relation of diet to toxicity received some attention, 

 but the question was not studied exhaustively in the present inves- 

 tigation. 



EXPERIMENTS ON RABBITS. 



Full-grown adult as well as young rabbits were employed. The diet consisted 

 either of carrots or of oats; water was given ad libitum. The rabbits were kept in 

 metal cages in a well-lighted and well-ventilated room. Unnecessary handling or 

 any other procedure tending to fatigue or to cause discomfort to the animals was 

 very carefully avoided, since we, had found that such treatment was likely to decrease 

 the resistance of the rabbit to caffein. The caffein was administered by feeding by 

 mouth and through a stomach tube, or by the subcutaneous method. In a good many 

 cases it was given daily, in some at longer intervals. 



SERIES A. 



The experiments of this series formed a preliminary study for the purpose of testing 

 the effect of moderate doses. One decigram of caffein per kilo was given daily for 

 several days; when administered at longer intervals the dose was increased to 150 to 

 200 mg per kilo. It was found that the smaller doses did not produce any symptoms; 

 even the weights of the animals were not influenced. Doses of medium size given on 

 two successive days were likewise without any noticeable effect (Nos. 182, 183, 123, 

 101). When a third dose of this size was given within 48 or 24 hours it proved fatal 

 (Nos. 123, 182, and 183). Exceptionally, however, moderately large doses (for rabbits) 

 may be given for three consecutive days without fatal issue, as in rabbit No. 101. 

 When given at intervals of two to three days, larger doses, as may be seen from the 

 protocols, can be administered without causing acute death (Nos. 173, 181, 201). 



The results of the tests of this series point to the absence of any accumulation and 

 to the possible elimination of moderate doses of caffein and its products of decom- 

 position within 24 hours or thereabouts. When the doses are larger the time of its 

 elimination is apparently longer, as shown by the fact that repetitions of the dose the 

 next day may be fatal, but when a longer interval is allowed it may be given without 

 causing death. It will be observed that only one rabbit of this series survived, but 

 it was extremely emaciated. This condition has been observed in a number of cases 

 after caffein had been given for several days. Even when the drug was withdrawn 

 the animals continued to lose weight. This may be explained by the condition of 

 the gastro-intestinal canal as found at autopsy. The presence of inflammation of the 

 mucous membrane of the stomach and intestines, with ulceration of the mucous mem- 

 brane of the pylorus in one of the rabbits (No. 173) of the series, in all probability 

 caused diminution or loss of appetite, which of itself would tend to cause loss of flesh 

 and strength and finally death. Protocols of the experiments follow. 



