Platelet-mediated cardiac ischemia.

Abstract

Although platelets have been associated with angina pectoris, myocardial infarction, and sudden death, the platelet's capacity for induction and propagation of cardiac ischemia remains incompletely defined. We therefore evaluated the effects of platelet activation occurring within the coronary circulation and tested the hypothesis that inhibition of platelet function would prevent platelet-induced cardiac ischemia. Human platelets were isolated from blood obtained from normal donors by Sepharose 2B column chromatography, resuspended in Hepes buffer, and added to the perfusate of a Langendorff rabbit heart (platelet counts greater than 10,000/microliters). Without, and with low dose (10 microM) prostaglandin E1 (PGE1), a reversible inhibitor of platelet function, immediate and irreversible global cardiac ischemia, as monitored by NADH fluorescent photography, ensued (N = 4) following platelet activation with thrombin (0.1 to 1 U/ml). Higher concentrations of PGE1 (0.1 to 1 mM, N = 2) or aspirin ingestion (1000 mg taken approximately 12, 4, and 1 hr prior to experiment, N = 2) completely prevented this platelet-induced myocardial ischemia. Aspirin, unlike PGE1, was effective despite its inability to block thrombin-induced platelet aggregation in our in vitro gel-filtered system. We conclude that activation of platelets within the coronary circulation is sufficient for induction of irreversible cardiac ischemia. The efficacy of aspirin, a cyclooxygenase inhibitor, further suggests that the products of arachidonate metabolism (e.g., thromboxanes) have a fundamental role in the genesis of platelet-mediated myocardial ischemia.

• Authors: V P Addonizio, L Wetstein, C A Fisher, P Feldman, J F Strauss 3rd, A H Harken
• Journal: The Journal of surgical research (J Surg Res) Vol. 33 Issue 5 Pg. 402-8 (Nov 1982) ISSN: 0022-4804 [Print] United States
• PMID: 7132326 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Prostaglandins E

Topics

• Animals
• Blood Platelets (drug effects, physiopathology)
• Blood Transfusion
• Coronary Circulation
• Coronary Disease (physiopathology)
• Humans
• Prostaglandins E (pharmacology)
• Rabbits