Hydroxyl radical scavenging effect of nicaraven in myocardial and coronary endothelial preservation and reperfusion injury

Objective: We investigated the efficacy of nicaraven in reducing myocardial as well as coronary endothelial preservation-reperfusion (P/R) injury. Methods: In experiment 1, isolated rat hearts were mounted on a Langendorff (L) apparatus to estimate the baseline cardiac function. Group 1, 8- and 12-h storage in histidine-tryptophan-ketoglutarate (HTK) solution; group 2, 8- and 12-h storage in HTK solution with superoxide dismutase (2.5 X 10(5) U/l) and catalase (2 X 10(5) U/l); group 3, 8- and 12-h storage in HTK solution with nicaraven (10(-3) M). Following storage for 8 and 12 h at 4 degrees C, they were reperfused and post-preservative cardiac function was evaluated. The hearts were then switched back to L-mode and paced at 330 beats/min. Coronary flow (CF) following perfusion with KHB solution containing 5-hydroxytryptamine (5-HT) and nitroglycerin was also measured. In experiment 2, segments of pig coronary artery were suspended in organ chambers and exposed to hydroxyl radicals in the presence or absence of nicaraven. The sensitivity of relaxation response to bradykinin of the prior-exposed rings was measured. Results: The recovery of CF and LV dp/dt following 8 h of storage in group 3 was higher than that in group 1, although there were no significant differences in the other parameters of cardiac functional recovery among the groups. The absolute values of cardiac function following 12 h of storage in groups 1-3 were as follows: 6.6 +/- 2.4, 9.1 +/- 0.8, 15.6 +/- 3.1 ml/min of cardiac output (CO); 1.9 +/- 0.9, 2.3 +/- 0.4, 6.0 +/- 2.3 ml/min of aortic flow (AF); 4.5 +/- 1.3, 6.0 +/- 0.5, 9.5 +/- 0.8 ml/min of CF, respectively. The recovery of CO, AF, CF, SP, MP, and left ventricular (LV) dp/dt were significantly improved in group 3, compared with those in group 1. CF and CO in group 3 were higher than those in group 2. 5-HT caused vasoconstriction in all groups, but the vasoconstriction in group 3 was less than in group 1. Prior exposure to FeSO4/H2O2 produced significant endothelial damage as reflected by the right-ward shift of the dose-response curve of bradykinin-induced endothelium-dependent relaxation. In the presence of nicaraven, the dose-response curve recovered to the control level. Conclusions: Nicaraven may improve coronary endothelial and myocardial function following P/R by its hydroxyl radical scavenging activity.