The role of nitric oxide and NO-donor agents in myocardial protection from 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 procedures requiring cardiopulmonary bypass and elective cardioplegia undergo repetitive episodes of ischemia and reperfusion, which leads to endothelial injury as well as contractile dysfunction and morphological 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 reperfusion with unmodified blood. Blood cardioplegia does not prevent this surgical 'reperfusion injury', but does prevent extension of endothelial injury during the period of hypothermic cardioplegic arrest ('protected ischemia'). It is not known whether global cardioplegic ischemia in preoperatively injured hearts impairs the basal release of nitric oxide (NO) and hence obtunds this endogenous protective mechanism. However, enhancement of blood cardioplegia with the NO precursor, L-arginine, reduces postsurgical myocardial injury, suggesting that endogenous or basal release of NO participates in the modulation of ischemic-reperfusion injury. In addition, an NO-donor agent also protects the myocardium from surgical ischemic-reperfusion injury. Both cardioprotective strategies involve inhibition of neutrophil accumulation, consistent with the known inhibitory effects of NO on neutrophil adherence and neutrophil-mediated damage to the coronary endothelium. Therefore, NO-related therapy offers a new strategy to protect the myocardium, including the coronary endothelium, from surgically imposed ischemic-reperfusion injury.