PHYSIOLOGY AND BIOCHEMISTRY OF SHOCK 405 



vascular clotting and shortens the clotting time, while on the other 

 hand, chymotrypsin prolongs the clotting time and does not clot blood, 

 and also plasma contains a trypsin inhibitor and there is no inhibitor 

 for chymotrypsin in serum, the differences in the effects of these two 

 enzymes were investigated. They found that a dose of 40 to 60 mg. of 

 chymotrypsin /kg. was lethal to dogs. At necropsy, no intravascular 

 blood-clots were found by microscopic examination. In contrast, a dose 

 of 10 to 50 mg. of trypsin/kg. was toxic for dogs. Post-mortem examina- 

 tion (2 mg. of trypsin/kg.) showed intravascular blood-clots. Absence 

 of blood-clotting or the prolongation of clotting time by chymotrypsin 

 was attributed to the possible digestion of fibrinogen and prothrombin 

 and thereby to their reduction in amounts, and to possible modification 

 of the physiological properties of the fibrinogen and prothrombin of 

 the plasma. 



Tagnon, et at. (1945), found that the initial effect on blood pressure 

 by chymotrypsin was much less than the rapid and marked fall in the 

 blood pressure produced by trypsin. 



d. The Question of the Proteolytic Liberation of Histamine as 

 Cause of Trypsin Shock. Emphasizing the similarities observed in 

 anaphylactic shock, and shock caused by histamine and proteolytic 

 enzymes, Rocha e Silva (1940a, 1941) reported demonstrating the 

 liberation of histamine (and other catabolic products) by the adminis- 

 tration of proteolytic enzymes to animals. Contraction was produced 

 by the action of trypsin on mammalian smooth muscles (intestine and 

 uterus of guinea pig, intestines of rabbit, cat, dog and mouse, and virgin 

 uterus of rat). Intravenous injection of trypsin produced effects result- 

 ing in the collapse and death of rabbits, dogs and cats. In cats and 

 rabbits the obstruction of the pulmonary circulation was deemed to be 

 responsible for tryptic shock. 



In experiments on perfusion of guinea pig lungs it was demonstrated 

 (Rocha e Silva, 1940b) that trypsin was capable of liberating histamine 

 from the tissues, and it was suggested that this may offer a basis for 

 understanding the pharmacological effects of trypsin. It was also re- 

 ported (Ramirez, et ah, 1940) that the injection of trypsin in dogs is 

 followed by an increase of the histamine-content of the blood plasma 

 due to the liberation from the liver of 6 to 10 mg. of histamine for the 



