GINKGO-BILOBA EXTRACT (EGB-761) IMPROVES POSTISCHEMIC FUNCTION IN ISOLATED PRECONDITIONED WORKING RAT HEARTS

Background: We studied the effect of preconditioning and Ginkgo biloba extract (EGb 761) in relation to the recovery of contractile function after global ischemia in the isolated working rat heart. Methods: Hea rts (n = 12 in each group) were randomly divided into five groups: In group I, hearts were subjected to 30 min of normothermic global ischem ia followed by 30 min of reperfusion; in group II, they were subjected to one cycle of preconditioning consisting of 5 min ischemia and 10 m in reperfusion before the induction of 30 min of ischemia and 30 min o f reperfusion; group III hearts underwent two cycles of preconditionin g; group IV hearts underwent three cycles of preconditioning; and grou p V hearts underwent four cycles of preconditioning before the onset o f 30 min ischemia followed by 30 min of reperfusion.Results: Ventricul ar fibrillation (total) and ventricular tachycardia (no preconditionin g) both fell from 100% to 50% (P < 0.05) after four cycles of precondi tioning. In relation to ventricular fibrillation, preconditioning sign ificantly reduced the formation of oxygen free radicals, measured by e lectron spin resonance spectroscopy (ESR), but recovery of cardiac fun ction was low in all preconditioned groups. Because of the relatively low incidence of arrhythmias (50% ventricular fibrillation and 50% ven tricular tachycardia) and relatively low cardiac function in Group V, EGb 761, a free-radical scavenger, was chosen to improve myocardial co ntractile function in preconditioned hearts. Fifty and 100 mg/kg of EG b 761 (per os) significantly improved coronary flow, aortic flow, left ventricular developed pressure (LVDP), and the first derivative of LV DP (LVDdP/dt(max)) in the four-cycle preconditioned group. Thus, after 30 min of reperfusion, aortic flow was improved from 11.6 +/- 0.9 ml/ min to 19.7 +/- 1.2 ml/min (P < 0.05) with a dose of 50 mg/kg of EGb 7 61 and to 22.0 +/- 1.5 ml/min (P < 0.05) with a dose 100 mg/kg of EGb 761, in the four-cycle preconditioned group. During reperfusion, the f ormation of free radicals was reduced by approximately 50 and 60% usin g 50 mg/kg and 100 mg/kg of EGb 761, respectively, when compared with the four-cycle preconditioned drug-free control group. Conclusion: We have demonstrated that EGb 761 can improve contractile function after global ischemia in the isolated working rat heart by reducing the form ation of oxygen free radicals, and we have shown that this protection is additive to that of ischemia-induced preconditioning.