The effects of the protease inhibitor, aprotinin, on the course of shock induced by endotoxin in cats.

The administration of endotoxin derived from Escherichia coli to anaesthetized cats resulted, within the first 5 min, in an initial increase in right atrial pressure and a reduction in systemic arterial blood pressure. Over the next 2 h shock was characterized by a reduced cardiac output, tachycardia, reduced arterial pH and an increased level of lactate. The survival rate at the end of the 8 h experimental period was only 10%. The protease inhibitor aprotinin (Trasylol), given as a continuous intravenous infusion 1000 kallikrein inhibitor units (k.i.u.) kg-1h-1 together with a bolus of 40,000 k.i.u. kg-1, significantly inhibited the severity and incidence of the initial endotoxin response (increase in right atrial pressure and systemic hypotension), perhaps suggesting the direct or indirect involvement of kinins. Aprotinin did not reduce the delayed effects of endotoxin (sustained reduction in cardiac output, lacticacidosis), nor did it improve survival at 8 h. Indeed, there was some evidence that aprotinin exaggerated the delayed effects of endotoxin in this model.