Role of platelet and vascular eicosanoids in the pathophysiology of ischemic heart disease.

The role of platelet and vascular arachidonate metabolism in ischemic heart disease can be derived from direct measurements and/or inhibitor trials. Direct measurements have yielded somewhat conflicting results, largely related to analytical problems and ex vivo platelet activation during blood sampling. On the other hand, inhibitor trials have clearly established the following: 1) thromboxane (TX) A2-dependent platelet activation plays an important role in the dynamic process of coronary thrombosis in unstable angina, 2) TXA2 does not appear to mediate coronary vasospasm, as seen in variant angina, 3) endogenous prostacyclin (PGI2) is not released in response to myocardial ischemia and is unlikely to regulate coronary blood flow, and 4) exogenous PGI2 is of limited therapeutic benefit. The demonstration that low-dose aspirin (0.5-1.0 mg/(kg X day] is a selective inhibitor of TXA2-dependent platelet function provides a conceptual and practical framework for the rational design of future trials. Moreover, the identification of major enzymatic metabolites of TXB2 in plasma (11-dehydro-TXB2) and urine (2,3-dinor-TXB2) and development of appropriate analytical techniques offer the opportunity for better defining the pathophysiological role of TXA2 in humans.