THE ROLE OF NITRIC-OXIDE AND NO-DONOR AGENTS IN MYOCARDIAL PROTECTIONFROM SURGICAL ISCHEMIC-REPERFUSION INJURY

The coronary vascular endothelium is injured by ischemia-reperfusion, which may facilitate the pathophysiological role played by neutrophils . Hearts undergoing coronary artery bypass surgery or other surgical p rocedures requiring cardiopulmonary bypass and elective cardioplegia u ndergo repetitive episodes of ischemia and reperfusion, which leads to endothelial injury as well as contractile dysfunction and morphologic al injury, despite the use of cardioprotective cardioplegic solutions and other strategies of myocardial protection. In cardiac surgery, as in coronary occlusion, endothelial injury seems to occur upon reperfus ion with unmodified blood. Blood cardioplegia does not prevent this su rgical 'reperfusion injury', but does prevent extension of endothelial injury during the period of hypothermic cardioplegic arrest ('protect ed ischemia'). It is not known whether global cardioplegic ischemia in preoperatively injured hearts impairs the basal release of nitric oxi de (NO) and hence obtunds this endogenous protective mechanism. Howeve r, enhancement of blood cardioplegia with the NO precursor, L-arginine , reduces postsurgical myocardial injury, suggesting that endogenous o r basal release of NO participates in the modulation of ischemic-reper fusion injury. In addition, an NO-donor agent also protects the myocar dium from surgical ischemic-reperfusion injury. Both cardioprotective strategies involve inhibition of neutrophil accumulation, consistent w ith the known inhibitory effects of NO on neutrophil adherence and neu trophil-mediated damage to the coronary endothelium. Therefore, NO-rel ated therapy offers a new strategy to protect the myocardium, includin g the coronary endothelium, from surgically imposed ischemic-reperfusi on injury.