Influence of aprotinin, a protease inhibitor, on porcine E. coli shock. Studies on coagulation, fibrinolytic and hemodynamic response.

The effect of a protease inhibitor, aprotinin, on hemostasis (a2M, a2AP, AT III, prothrombin-convertin activity, fibrinogen, fibrinogen monomers and fibrinolytic activity on fibrin plates) was investigated in pigs with septic shock. Anesthetized pigs were given live Escherichia coli i.v. (n = 7), or aprotinin (1,000,000 KIE i.v.) 15 min before live E. coli (n = 6), or Ringer's solution only (sham controls, n = 8). Septic shock developed in all E. coli-infused pigs. Pulmonary vascular resistance increased, platelet and leukocyte counts fell and signs of systemic activation of the coagulation and fibrinolytic systems appeared in the E. coli groups, but aprotinin attenuated the effects on these systems and also on the pulmonary circulation. Five of the six aprotinin-pretreated pigs survived, but none of the seven with septic shock and no pretreatment. Thus the shock induced by infusion of live E. coli and the resultant changes in the coagulation and fibrinolytic systems and in cardiopulmonary hemodynamics were diminished by aprotinin pretreatment.