title: Mediation of cardiac ischemia by thromboxanes released from human platelets.
abstract: We evaluated the consequences of platelet activation within the coronary circulation and determined the contribution of released thromboxanes, the most potent vasoconstrictors known, to the ensuing cardiac ischemia. Human platelets were isolated by sepharose column chromatography from blood of normal donors and added to the crystalloid perfusate of a Langendorff rabbit heart (platelet counts greater than or equal to 10,000/microliters). Following thrombin-induced (1 U/ml) platelet activation, the coronary flow decreased by 30 +/- 10% (mean +/- SEM, P less than 0.02), the mean concentration of thromboxane B2 in the coronary sinus effluent rose to 62 +/- 25 pmol/ml, and immediate, often irreversible cardiac ischemia as monitored by nicotinamide adenine dehydrogenase autofluorescence photography, ensued. However, with high concentrations of the platelet inhibitor and vasodilator, prostaglandin E1 (1.0 mM), the coronary flow increased by 50 +/-= 15%, and the epicardial fluorescence remained unchanged despite a small (10 +/- 3 pmol/ml) increase in coronary sinus thromboxanes. Platelets isolated from donors who ingested aspirin were incapable of thromboxane synthesis (less than 5 pmol/ml) but remained normally responsive to thrombin-induced activation. When these platelets were challenged by thrombin during cardiac perfusion, however, coronary flow and epicardial fluorescence remained unchanged. We conclude that platelet activation within the coronary circulation can induce irreversible cardiac ischemia, which, however, can be prevented by appropriate pharmacologic inhibition of platelet function. Furthermore, the fact that cardiac perfusion was preserved during a thrombin challenge of platelets from aspirin-treated donors establishes a fundamental role for the products of cyclooxygenase activity (e.g., thromboxanes) in the genesis of this form of myocardial ischemia.
mesh_terms: D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D011464:Epoprostenol / Q000494:pharmacology; D005453:Fluorescence; D006801:Humans; D010781:Photography; D011458:Prostaglandins E / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013931:Thromboxanes / Q000378:metabolism / Q000502:physiology*
chemical_list: D011458:Prostaglandins E; D013931:Thromboxanes; D011464:Epoprostenol; D013917:Thrombin; D001241:Aspirin