Liberation of Histamine by Trypsin

Rocha e Silva 1 has reported that trypsin has the capacity of liberating histamine when perfused through the guinea pig lungs and postulates that the toxicity of trypsin when injected intravenously in intact animals may be due to this effect. The present report is concerned with confirming his findings on the isolated perfused guinea pig lung and of reporting observations on the liberation of histamine in intact dogs following its intravenous administration.

The isolated lungs of guinea pigs were perfused through the pulmonary artery with Sollmann-Rademaeker's solution according to the method of Feldberg and Kellaway. 2 They were rhythmically ventilated with air throughout the experiment. After a control per fusion of about 30 minutes a small amount of trypsin was injected into the afferent cannula and the perfusate then tested for histamine activity. Two highly active, but not crystalline, preparations of trypsin were used in amounts from 0.5 to 10 mg. In the experiments done to date the smaller dosage occasionally led to the appearance of histamine activity in the perfusate, while doses of more than 1.0 mg did so regularly. Since this experiment is essentially confirmatory of the findings of Rocha e Silva, further details are omitted.

Four dogs were anesthetized with ether and barbital, and arranged tor the recording of blood pressure tracings. Normal blood samples were obtained and then trypsin was injected intravenously in. doses of 2 to 5 mg per kilo. Blood samples were obtained 2 to 5 minutes after the injection and all samples of blood then assayed for their histamine content by the method of Barsoum and Gaddum 3 as modified by Code. 4 In one experiment there was but a slight increase in the blood histamine, in 2 experiments there was a moderate increase and in one experiment there was a very marked increase from a normal value of no detectable histamine to a level of 1.8 γ of histamine base per cc after the trypsin injection.