406 IMMUNO-CATALYSIS 



whole organ. A similar amount of histamine is reported to be discharged 

 from the liver of dogs following anaphylactic shock (Ojers, et ah, 1941 )• 

 Rocha e Silva and Andrade (1943) reported results indicating the 

 liberation of histamine from rabbit blood cells by the action of papain. 



However, the hypothesis that trypsin shock is a consequence of 

 tryptic liberation of histamine has recently been questioned. Wells, 

 et al. (1946) reinvestigated the question of the toxicity of trypsin in 

 relation to histamine liberation and arrived at the following conclu- 

 sions. Guinea pigs dying from the intravenous injection of trypsin fail 

 to show either the rise in blood histamine or the emphysematous lungs 

 characteristic of the liberation and action of histamine. In these experi- 

 ments, benadryl (beta-dimethylaminoethylbenzhydryletherhydrochlo- 

 ride), which is a potent antagonist to either administered or liberated 

 histamine, afforded neither the guinea pig nor the dog any significant 

 protection against the lethal action of intra\'enously injected trypsin. 

 In other experiments, they found that benadryl is much less effective 

 in reducing the blood pressure response to trypsin than it is in reduc- 

 ing the response to histamine. Determining the blood histamine before 

 and during tryptic shock in the dog they concluded that in none of 

 these animals was the blood histamine of sufficient magnitude to ex- 

 plain the severity of the reaction produced. Only in one dog was a 

 rise in blood histamine observed. They reported that the amount of 

 histamine released during the perfusion of dog's liver is very small. And 

 the liberation of histamine from isolated guinea pig lungs by per- 

 fusion with trypsin solutions is deemed to be of no consequence to the 

 toxicity of trypsin in the intact animal in view of the absence of any 

 pulmonary effects of histamine when trypsin is injected into the intact 

 animal. 



The effective prevention of the action of trypsin on isolated smooth 

 muscle by arginine as due to an antagonism of arginine to liberated 

 histamine is questioned. They suggest that the trypsin itself may be 

 antagonized by arginine. They reject the idea that the positive "trypan- 

 blue reaction" produced by trypsin is an indication of the liberation and 

 action of histamine. In view, also, of the findings of Tagnon (1945) 

 that intravascular clotting by trypsin injected intravenously may play 

 a significant role in the elaboration of the toxic symptoms noted, the 

 histamine hypothesis, relative to the toxicity of trypsin, is considered 

 doubtful. 



