210 WARFIELD T. LONGCOPE AND GEORGE M. MACKENZIE 



output after anaphylactic shock in dogs. Segale, too, found increased 

 nitrogen excretion after reinjection of sensitized animals an increase 

 which continued for three days. Leschke(a) (6) also investigated this 

 question, studying particularly the nitrogen metabolism, gas exchange and 

 temperature reactions in anaphylaxis. Using Friedberger's anaphylatoxin, 

 he administered to dogs sufficient amounts to produce symptoms but not 

 death. Animals treated in this way showed no evidence, judged by the 

 urinary nitrogen, of increased protein metabolism. Further experi- 

 ments with active anaphylaxis yielded similar results. He concludes that 

 the anaphylactic poison primarily depresses protein metabolism and total 

 metabolism, and that this depression occurs no matter whether there is a 

 rise or fall of body temperature after the intoxicating dose. He criti- 

 cises the results of Manoiloff and Segale on the ground that these investi- 

 gators ignored the effect on the protein metabolism of the concomitant 

 phenomena motor activity, spasms, convulsions, respiratory and circula- 

 tory disturbances. He holds that the evidence of accelerated protein 

 metabolism obtained by Segale and Manoiloff was due to these phenomena 

 of the reaction and not to any direct action of the anaphylactic poison. 

 The validity of this criticism is questionable. Unless the fat and carbo- 

 hydrate stores of the body are exhausted by starvation or exercise, or for 

 some other reason become less available, motor activity, unless long con- 

 tinued, does not increase the combustion of protein. Pettenkofer and Voit 

 first demonstrated this fact, and later it was confirmed quite conclusively 

 by Krummacher. Kocher, indeed, states that doubling the heat produc- 

 tion of the day as by walking 60 kilometers has little or no influence on 

 the protein metabolism of man. The method of sensitization used by 

 Leschke, furthermore, makes it seem probable that his animals were in a 

 state of anti-anaphylaxis during the test period. 



It is apparent from these discordant results obtained by different 

 workers in studying the disturbances of protein metabolism during anaphy- 

 lactic reactions that there must be unrecognized sources of error. Leschke 

 himself emphasizes the possibility of variable effects according to the 

 size of the sensitizing dose, the interval between sensitizing and intoxicat- 

 ing doses, the amount of antibodies formed, the size of the reinjection dose 

 and the method of administration. But there is another important objec- 

 tion to which the investigators whose work we have referred to have given 

 scant or no attention. All their conclusions were based on studies of 

 urinary nitrogen only, apparently with the assumption that renal function 

 was undisturbed. To what extent renal function also was affected by the 

 lesions observed by Longcope and Boughton after repeated anaphylactic 

 shocks was not studied, but with such marked anatomical changes it is 

 highly probable that function also was impaired. Such being the case, 

 one should be cautious in drawing conclusions regarding protein metabol- 

 ism after reinjection of animals sensitized by repeated doses of a foreign 



