title: Potential of combined thromboxane A2 and serotonin antagonists to prevent the development of unstable angina and acute myocardial infarction.
abstract: We have previously speculated that the abrupt conversion from chronic stable angina to unstable angina and the subsequent progression to acute myocardial infarction may result from myocardial ischemia caused by progressive platelet aggregation and dynamic coronary vasoconstriction. In turn, platelet aggregation and dynamic vasoconstriction probably result from the local accumulation of thromboxane A(2) and serotonin at sites of coronary artery stenosis and endothelial injury; they may also result from relative decreases in the local concentrations of endothelium-derived vasodilators and inhibitors of platelet aggregation, such as endothelium-derived relaxing factors and prostacyclin. Because of severe reductions in coronary blood flow caused by these mechanisms, platelet aggregation may increase, and an occlusive thrombus-composed of platelets, leukocytes, and red blood cells in a fibrin mesh-may develop. When coronary arteries are occluded or narrowed by these mechanisms for a sufficient time, the result may be myocardial necrosis, electrical instability, or sudden death. With respect to the process of coronary artery thrombosis and vasoconstriction, we believe that unstable angina and acute myocardial infarction are 2 elements in a continuum. When platelet aggregation or dynamic vasoconstriction at sites of endothelial injury and coronary stenosis is brief, unstable angina or non-Q-wave infarction may occur. When coronary obstruction by these mechanisms is prolonged for several hours, however, Q-wave myocardial infarction results. Future clinical studies should provide further insights into these and additional mediators and mechanisms that may effect the abrupt transition from chronic to acute coronary disease syndromes in human beings.
authors.affiliation: The Department of Internal Medicine, University of Texas Medical School at Houston, Houston, Texas, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Willerson
authors.forename: L M
authors.initials: LM
authors.lastname: Buja