Cardioprotective effects of hexasulfobutylated C60 (FC4S) in anesthetized rats during coronary occlusion/reperfusion injury

The effects of hexasulfobutylated C-60 (FC4S) on (1) coronary occlusion/reperfusion and (2) isolated aortic ring preparation of rats were studied in vivo and in vitro. In the in vivo studies, FC4S (1-10 mug/kg, iv) reduced the incidence and duration of ventricular tachycardia and ventricular fibrillation during the coronary artery occlusion phase and the reperfusion phase. FC4S increased nitric oxide (NO) and decreased lactate dehydrogenase in plasma during the period of cardiac ischemia and reperfusion. In animals subjected to 4 In of coronary occlusion, pretreatment with FC4S (110 mug/kg, iv) reduced the cardiac infarct zone (expressed as percent of area at risk) from 39.7 +/- 4.8% to 11.3 +/- 4.1 %. Mortality during cardiac ischemia and reperfusion was completely prevented after injection of FC4S (10 mug/Kg iv). In the isolated endothelium-containing aortic ring preparation, phenylephrine (PE) elicited contractions and FC4S elicited a significant relaxing effect on PE-precontracted aortic rings. This relaxing effect of FC4S was reduced by pretreatment with N(G)-nitro-L-arginine methyl ester (1 mM), a blocker of NO synthase. It is concluded that FC4S may be useful as a potential cardioprotective agent for cardiac ischemia and reperfusion. The beneficial effect of FC4S may be partly correlated with its antioxidant property and also by the upregulation of NO production and vasodilation effects. (C) 2001 Wiley-Liss, Inc.