Abstract
During cardiac surgery, ischemia-reperfusion injury (IRI) is thought to be a major factor in intraoperative myocardial damage. Coronary endothelial cells have been thought to play an important role in the pathogenesis of cardiac IRI. Release of nitric oxide (NO) from coronary endothelial cells is impaired following myocardial ischemia, and this may contribute to the vulnerability of the coronary circulation to thrombus-formation and vasospasm. Several experimental studies have found that NO has a cardioprotective effect in myocardial IRI. In this regard, attempts have been made to supplement NO production exogenously during reperfusion, when endogenous NO release from endothelial cells may be diminished. In a blood-reperfused heart model, L-arginine acts cardioprotectively via 2 primary possible mechanisms: (1) by blocking both neutrophil aggregation and neutrophil adherence, and (2) by scavenging oxygen-derived free-radicals. On the other hand, in a non-blood reperfused heart model, the optimal concentration of L-arginine may be low and protection may be due to 2 additional mechanisms: (3) direct coronary vasodilatation and (4) reduced oxygen demand due to vasodilatation-induced hypotension. Other studies have suggested that NO exacerbates IRI and that NO synthase (NOS) inhibitors act cardioprotectively. It has also been suggested that the pharmacological effectiveness of inhibiting NO production may be due to the prevention of peroxinitrite formation from NO and superoxide during reperfusion. This review summarizes the current understanding of the role of NO in IRI. (Jpn Circ J 1997; 61: 119 - 132)
