Role of thromboxanes and prostaglandin endoperoxides in the pathogenesis of eicosanoid induced sudden death.

Arachidonic acid (1 mg/kg) or 9,11-azo PGH2 (35 micrograms/kg) injected intravenously into anesthetized rabbits results in sudden death characterized by a marked loss of circulating platelets, a dramatic rise in circulating thromboxane B2 concentrations and a precipitous drop in blood pressure. Death ensues in 3 to 5 minutes from pulmonary thrombosis and pulmonary artery constriction. Administration of dazoxiben (2 mg/kg) prior to arachidonic acid, prevents all of these changes. However, dazoxiben failed to prevent any of these effects after injection of azo-PGH2, a synthetic agonist of the endoperoxide and thromboxane receptor. These results demonstrate the importance of endoperoxide-thromboxane accumulation in eicosanoid induced sudden death and suggests that there is no significant functional difference between the actions of these agents in the rabbit.