Nonami Y
Department of Surgery II, Kochi Medical School, Japan.
Jpn Circ J. 1997 Feb;61(2):119-32. doi: 10.1253/jcj.61.119.
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.
在心脏手术期间，缺血再灌注损伤（IRI）被认为是术中心肌损伤的一个主要因素。冠状动脉内皮细胞被认为在心脏IRI的发病机制中起重要作用。心肌缺血后，冠状动脉内皮细胞释放一氧化氮（NO）受损，这可能导致冠状动脉循环易形成血栓和发生血管痉挛。多项实验研究发现，NO在心肌IRI中具有心脏保护作用。在这方面，人们尝试在再灌注期间外源性补充NO的生成，此时内皮细胞的内源性NO释放可能减少。在血液再灌注心脏模型中，L-精氨酸通过两种主要可能机制发挥心脏保护作用：（1）通过阻断中性粒细胞聚集和中性粒细胞黏附，以及（2）通过清除氧衍生的自由基。另一方面，在非血液再灌注心脏模型中，L-精氨酸的最佳浓度可能较低，保护作用可能归因于另外两种机制：（3）直接冠状动脉血管舒张和（4）由于血管舒张引起的低血压导致的氧需求降低。其他研究表明，NO会加重IRI，而一氧化氮合酶（NOS）抑制剂具有心脏保护作用。也有人提出，抑制NO生成的药理作用可能是由于在再灌注期间防止了由NO和超氧化物形成过氧亚硝酸盐。本综述总结了目前对NO在IRI中的作用的理解。
