Reduction of the cardiopulmonary response to endotoxin by the administration of aprotinin.

The antiprotease aprotinin (Trasylol) (20,000 KIU bolus/kg followed by 10,000 KIU/(kg x h) for 8 h) was administered to sheep which were then given a continuous dose of endotoxin (24 ng/(kg x h) for 24 h). Their cardiopulmonary response was compared to a group of sheep which received endotoxin alone as well as a sham group which received neither endotoxin nor aprotinin. The response to endotoxin was characterized by an increased lung lymph flow and cardiac output. This response was blocked by the administration of aprotinin. In the endotoxin group there was a fall in prekallikrein levels. The action of aprotinin suggests that the cardiopulmonary response to endotoxin may be mediated by the formation of bradykinin.