Effects of EGb 761 on nitric oxide and oxygen free radicals, myocardial damage and arrhythmia in ischemia-reperfusion injury in vivo.

The cardioprotective effects of EGb 761 on the release of nitric oxide (NO), the concentration of serum thiobarbituric acid reaction substance (TBARS), the activity of creatine kinase (CK) and the incidence of ventricular arrhythmias were investigated in myocardial ischemia-reperfusion injury in vivo. Using sodium nitrite (NaNO2) as standard source of nitric oxide (NO), we compared the correlation coefficients of the three measuring methods used currently in the determination of NOFe2+(DETC)2 complex with that of the measuring method suggested in this study. The result showed that measuring the whole height of three splitting signals is the best linear correlation to the concentration of NO comparing with other methods in this system. Using this method, we observed the effects of EGb 761 on NOFe2+(DETC)2 complex in myocardial ischemia-reperfusion injury in vivo. The hearts of the Wistar rats were subjected to 30 min of ischemia and 10 min of reperfusion in vivo. Different doses of EGb 761 (25, 50, 100, 200 mg/kg i.p.), superoxide dismutase (SOD, 10(4) U/kg), l-arginine (50 mg/kg i.p.) and nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine (NNA, 50 mg/kg i.p.) were administered to the ischemia-reperfusion rats. EGb 761 under the dose of 100 mg/kg increased the signal intensity of NOFe2+(DETC)2 complex, while EGb 761 at 200 mg/kg showed an effect of decreasing the signal intensity of NOFe2+(DETC)2 complex. EGb 761 inhibited the formation of TBARS, the release of CK, and mitigated the incidence of ventricular arrhythmias in a dose dependent way. Both l-arginine and SOD increased the signal intensity of NOFe2+(DETC)2 complex and inhibited the formation of TBARS, the leakage of CK and the incidence of ventricular arrhythmia. NNA not only had no protective effects on myocardial injury, but also increased the incidence of reperfusion-induced arrhythmia. In conclusion, EGb 761 has cardiovascular protective effects by means of adjusting the level of NO and inhibiting oxygen free radicals induced lipid peroxidation in myocardial ischemia-reperfusion injury in vivo.