THE EFFECTS OF PROSTACYCLIN (PGI2) ON ENDOTOXIN-SHOCK AND ENDOTOXIN-INDUCED PLATELET-AGGREGATION IN DOGS

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 7  (3) , 299-308
Abstract
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. The efficacy of prostacyclin in endotoxin shock and on endotoxin-induced platelet aggregation was determined in dogs. Thrombocytopenia is characteristic of septic shock and is possibly related to platelet clumping and thus to the pathophysiology of endotoxin shock. Male dogs (124) were given an LD50 dose of Escherichia coli endotoxin (1 mg/kg); 12 were treated with PGI2 (20 ng/kg per min) by continuous infusion from 15 min before and for 4 h 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, 42% (5/12) survived; with PGI2 treatment 83% (10/12) survived (P < 0.05). Prostacyclin therapy did not alter the rise in pulmonary arterial pressure but further decreased the mean systemic arterial pressure. There was a transient attenuation of the thrombocytopenia and minimal effects on the granulocytopenia. The PGI2-treated animals had greater decreases in blood pressures but 83% of the animals survived. 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 .mu.g/ml) and aspirin (0.2-1 .mu.g/ml), PG[prostaglandin]E1 (0.1-1 .mu.g/ml) and PGI2 (0.1-1 .mu.g/ml), added 1 min before endotoxin (1 .mu.g/ml) had no apparent effect on the endotoxin-induced platelet aggregation. Endotoxin-induced platelet aggregation may be caused by a mechanism that is unrelated to cAMP and/or the arachidonic acid PG system.