Experiences with allopurinal in canine endotoxin shock.

Allopurinol, a xanthine-oxidase inhibitor and potential cell-stabilizing compound, was studied as a possible therapeutic agent in canine endotoxin shock. Circulatory collapse was produced in anesthetized mongrel dogs by IV administration of an LD75 dose of endotoxin. Treatment, with dextran alone, or with dextran and an IV bolus of allopurinol, was initiated 15 minutes after the onset of shock. The administration of 25, 50, or 100 mg/kg of IV allopurinol, accompanied by adequate volume replenishment, produced a significant reduction in the total peripheral vascular resistance and significant increases in cardiac output, blood glucose concentration, and arterial lactate concentration. Survival was not enhanced by allopurinol therapy, and allopurinol administration in normal dogs did not affect the vascular tone or the arterial lactic acid concentration. There was a transient hyperglycemic response and a decrease in the cardiac index in normal animals. The infusion of a postassium-insulin solution, in association with 100 mg/kg of allopurinol, did not significantly improve survival. In summary, although a number of potentially beneficial hemodynamic and metabolic effects were observed following allopurinol administration, survival in canine endotoxin shock was not enhanced.