Coronary artery ischemia initiated by occlusion or thrombus formation produces myocardial ischemia that can ultimately result in myocardial cell injury and necrosis of the myocardium. Current clinical strategies for the treatment of acute myocardial ischemia include coronary angioplasty, directional coronary atherectomy, and the administration of thrombolytic agents to restore blood flow to the ischemic myocardium. While coronary reperfusion can salvage ischemic tissue, it may in itself also contribute to coronary vascular and myocardial cell injury (1-4). Myocardial reperfusion after coronary artery ischemia accelerates the necrosis of reversibly injured cardiac myocytes by enhancing cell swelling, the disruption of cell ultrastructure, formation of contraction bands, and the influx of calcium and other ions (2, 3). Recent experimental evidence strongly suggests that coronary artery endothelial dysfunction may be an early trigger for neutrophil-mediated myocardial reperfusion injury (4-7). Nitric oxide (NO.) release by the coronary vasculature is impaired within 5 mins after reperfusion of ischemic myocardium and results in a profound loss of vascular homeostasis (7). Polymorphonuclear neutrophils (PMN) begin to accumulate within the ischemic-reperfusion myocardium as a result of diminished coronary NO. release; activated PMNs then mediate myocardial cell injury and necrosis (6, 7). Novel therapeutic strategies aimed at the preservation or replenishment of coronary NO. concentrations may prove beneficial in the treatment of myocardial reperfusion injury in the future.(ABSTRACT TRUNCATED AT 250 WORDS)