Enhanced platelet accumulation onto injured carotid arteries in rabbits after aspirin treatment.
Prostacyclin (PGI2) is a powerful inhibitor of platelet aggregation, but its role in the pathogenesis of arterial thrombosis is uncertain. We have studied the thrombogenic effect of inhibiting PGI2 production by aspirin (ASA) in carotid arteries of rabbits given 0, 3, 10, or 100 mg ASA/kg either 1, 3, 6, or 20 h beforehand. Platelet accumulation onto injured carotid arteries was enhanced with ASA in a dose of 10 mg/kg. A higher dose of ASA (100 mg/kg) had no further effect. The enhanced thrombogenic effect of ASA persisted for at least 20 h and was associated with a decrease in vessel wall PGI2 production. There was a strong inverse correlation (r = 0.55, P less than 0.01) between PGI2 production and platelet accumulation. The findings suggest that the margin of safety in obtaining an antithrombotic effect of ASA and producing a potential thrombotic effect in arteries may not be as large as predicted by studies using cultured endothelial cells or experimentally induced thrombosis in veins.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects / Q000648:ultrastructure; D020212:Carotid Artery Injuries; D002341:Carotid Artery Thrombosis / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism; D008854:Microscopy, Electron; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D013928:Thromboxane A2 / Q000378:metabolism; D013997:Time Factors
D013928:Thromboxane A2; D011464:Epoprostenol; D001241:Aspirin