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

Abstract

Abstract The effects of hexasulfobutylated C 60 (FC 4 S) 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, FC 4 S (1–10 μg/kg, iv) reduced the incidence and duration of ventricular tachycardia and ventricular fibrillation during the coronary artery occlusion phase and the reperfusion phase. FC 4 S increased nitric oxide (NO) and decreased lactate dehydrogenase in plasma during the period of cardiac ischemia and reperfusion. In animals subjected to 4 h of coronary occlusion, pretreatment with FC 4 S (10 μg/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 FC 4 S (10 μg/Kg iv). In the isolated endothelium‐containing aortic ring preparation, phenylephrine (PE) elicited contractions and FC 4 S elicited a significant relaxing effect on PE‐precontracted aortic rings. This relaxing effect of FC 4 S was reduced by pretreatment with N (G)‐nitro‐ L ‐arginine methyl ester (1 mM), a blocker of NO synthase. It is concluded that FC 4 S may be useful as a potential cardioprotective agent for cardiac ischemia and reperfusion. The beneficial effect of FC 4 S may be partly correlated with its antioxidant property and also by the upregulation of NO production and vasodilation effects. Drug Dev. Res. 53:244–253, 2001. © 2001 Wiley‐Liss, Inc.