Mechanisms of myocardial ischemia

Myocardial ischemia occurs as a result of an imbalance between tissue oxygen supply and demand. The clinical correlates of the syndrome include classic unstable and Prinzmetal variant angina. Although controversial, it has been postulated that the pathogenesis of unstable angina involves a combination of (1) fixed atherosclerotic coronary artery stenosis, (2) dynamic coronary artery obstruction mediated by coronary vasospasm, and (3) platelet aggregation promoting intracoronary thrombotic occlusion. The authors review evidence to support the conclusion that the interaction of these processes may be mediated by an imbalance in the levels of two eicosanoids, thromboxane A2 (TxA2) and prostacyclin (PGI2), which are responsible for platelet-vascular wall homeostasis. TxA2 is a powerful endogenous vasoconstrictor and promoter of platelet aggregation, whereas PGI2 has diametrically opposed, protective actions. Management and preventive strategies for unstable angina have, therefore, concentrated on the pharmacologic and dietary prohibition of TxA2 activity by agents targeted at inhibiting its synthesis and antagonizing its actions. These agents are discussed and differentiated.