Peroxynitrite formation from human myocardium after ischemia-reperfusion during open heart operation

Background. Current experimental studies have demonstrated that peroxynitrite (ONOO−) has both cytotoxic and cytoprotective effects on myocardial ischemia-reperfusion injury. However, even myocardial ONOO− formation has not yet been investigated in humans undergoing open heart operation. We measured plasma nitrotyrosine as an indicator of ONOO− formation during open heart operation and examined its association with myocardial ischemia-reperfusion injury. Methods. Twenty adult patients undergoing mitral valve replacement under cardiopulmonary bypass between 1997 and 1998 were enrolled in this study (6 men and 14 women). Arterial blood (Ao) and coronary sinus effluent (CS) were obtained: (1) before the initiation of cardiopulmonary bypass, (2) just after aortic unclamping, (3) at 5 minutes, (4) at 10 minutes, (5) at 15 minutes, and (6) at 20 minutes after aortic unclamping. Results. At every sampling point after reperfusion, plasma nitrate and nitrite was significantly lower in CS than in Ao, and the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr; an index of ONOO− formation) was significantly higher in CS than in Ao. The CS-Ao difference in %NO2-Tyr, myocardium-derived ONOO−, reached its peak at 5 minutes after reperfusion (2.17 ± 0.74%), which was significantly correlated with the peak CS-Ao difference in plasma malondialdehyde, and with postoperative maximum creatine kinase-MB. Conclusions. These results first demonstrate that ONOO− is produced from human myocardium after ischemia-reperfusion during open heart operation, and myocardium-derived ONOO− can be determined by the CS-Ao difference in %NO2-Tyr.