The effects of prostacyclin (PGI2) on endotoxin shock and endotoxin-induced platelet aggregation in dogs.

Prostacyclin (PGI2) is a major metabolite of arachidonic acid and is synthesized in vascular endothelial cells. It is a potent inhibitor of platelet aggregation and a known vasodilator. Because of the effects of PGI2 on platelet function, this study was designed to determine the efficacy of prostacyclin in endotoxin shock and on endotoxin-induced platelet aggregation in dogs. Thrombocytopenia is characteristic of septic shock and is believed to be related to platelet clumping, and thereby, to participate in the pathophysiology of endotoxin shock. Twenty-four males dogs were given an LD50 dose of Escherichia coli endotoxin (1 mg/kg). Twelve of these animals were treated with PGI2 (20 ng/kg/min) by continuous infusion from 15 minutes before, and for 4 hours after the injection of endotoxin. Parameters determined were mean arterial pressure, cardiac output, pulmonary arterial pressure, heart rate, platelet and white blood cell counts, and arterial blood gases. In animals given endotoxin alone, only 42% (5/12) survived, whereas, with PGI2 treatment, 83% (10/12) survived (P < 0.05). Prostacyclin therapy did not alter the rise in pulmonary arterial pressure, but did further decrease the mean systemic arterial pressure. There was a transient attenuation of the thrombocytopenia, and minimal effects on the granulocytopenia. Despite the fact that the PGI2-treated animals had greater decreases in blood pressures, 83% of the animals did survive. These findings suggest that PGI2 may have some protective effects in endotoxin shock. Serratia marcescens endotoxin caused dose-dependent platelet aggregation in canine platelet-rich plasma in vitro. Antiaggregating agents such as indomethacin (0.2-1 microgram/ml), and aspirin (0.2-1 microgram/ml), PGE1 (0.1-1 microgram/ml) and PGI2 (0.1-1 microgram/ml), added 1 minute before endotoxin (1 microgram/ml), had no apparent effect on the endotoxin-induced platelet aggregation. These findings suggest that endotoxin-induced platelet aggregation may be caused by a mechanism that is unrelated to cAMP and/or the arachidonic acid prostaglandin system.