The Role of Nitric Oxide in Ischemia-Reperfusion

Considering the prevalence of ischemic cardiovascular disorders and the advent of thrombolytic therapies, percutaneous transluminal angioplasty, vascular bybass, and organ transplantation, ischemia and reperfusion of a vascular bed have become routine in the development, progression, and treatment of numerous cardiovascular disease states. The possibility that the reestablishment of blood flow in a previously ischemic region might injure cells that were viable at the time of reperfusion was suggested in the late 1970s (1) and later defined by Rosenkranz and Buckberg (2), and Braunwald and Kloner (3). Since that time, the pathophysiology of ischemia-reperfusion has been studied intensively and the series of events involved in this phenomenon are now more clearly defined. Ischemia-reperfusion produces tissue injury that is apparent within several hours of reperfusion and involves two distinct yet interrelated phases. These have been described as an endothelial triggering phase and a neutrophil amplification phase (4), both of which are closely linked to endothelium-derived nitric oxide (NO·).