20 CAFFEIN IN NEPHRECTOMIZED RABBITS. 



the kidney as a result of anaesthesia, for it was found (Bulletin 157) 

 that the elimination of caffein in rabbits normally begins 15 to 40 

 minutes after its subcutaneous injection. It is interesting to note 

 that the bile contained very small quantities, only milligram quanti- 

 ties being found in the normal rabbit as well as in the rabbit without 

 kidneys. 



The kidneys and intestines, and to a much smaller extent the stom- 

 ach, are therefore the chief organs for the elimination of caffein. It is 

 important to appreciate, however, that the role which the gastro- 

 intestinal canal plays in this connection is quite different from that 

 of the kidney. Although, like the latter, it relieves the circulation and 

 probably other organs in the body of a considerable amount of caffein, 

 this action is really not excretory in nature, for the caffein is stored 

 only temporarily in the lumen of the intestines or stomach only to be 

 returned gradually to the circulation, as very small amounts of caffein 

 were removed in the feces. The function of the digestive tract is hi 

 this case more nearly akin to that which the liver possesses for numer- 

 ous substances. Hence even the removal of the kidney fails to trans- 

 form the stomach and kites tines into true organs for the excretion of 

 caffein; the results obtained in the present investigation indicate that 

 after double nephrectomy there is merely an increase in the activity 

 of the mechanism which existed in the normal rabbit. It is evident, 

 therefore, that a formation de novo of a mechanism for the elimination 

 of foreign substances does not take place under these conditions. 

 Observations on the bile show that even if a mechanism exists in 

 the normal subject but is poorly developed, it apparently remains 

 unchanged after nephrectomy. The conflicting views held by inves- 

 tigators as regards the development of vicarious elimination by the 

 wall of the gastrointestinal canal are perhaps due to lack of appre- 

 ciation that vicarious action may consist in the stimulation of a pre- 

 viously existing function to greater activity. 



TOXICITY OF CAFFEIN IN NEPHRECTOMIZED RABBITS. 

 INTRODUCTION. 



In the experiments of the preceding section it was noticed that 

 moderately large doses of caffein failed to produce a fatal result. 

 Indeed, in some rabbits there was no manifestation of symptoms after 

 the administration of 150 mg of caffein per kilo, while in Series IV 

 rabbits which received 200 mg per kilo lived 24 to 28 hours before they 

 were killed. It is interesting to recall that in a previous study 

 (Bureau of Chemistry Bui. 148) 200 mg per kilo proved toxic, 

 although not necessarily fatal in most cases for normal rabbits. 

 Retarded absorption might be given as a cause for the greater resist- 

 ance to caffein, but the appearance of symptoms of caffein intoxi- 



