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 substan ce (TBARS), the activity of creatine kinase (CK) and the incidence of ventricular arrhythmias were investigated in myocardial ischemia-reper fusion 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 spl itting 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), complex in myocardial ischemia-reperfusion injury in vivo. The hearts of the Wistar rats we re 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 d ismutase (SOD, 10(4) U/kg). L-arginine (50 mg/kg i.p.) and nitric oxid e synthase (NOS) inhibitor N-G-nitro-L-arginine (NNA, 50 mg/kg i.p.) w ere administered to the ischemia-reperfusion rats. EGb 761 under the d ose of 100 mg/kg increased the signal intensity of NOFe2+ (DETC)(2) co mplex, while EGb 761 at 200 mg/kg showed an effect of decreasing the s ignal intensity of NOFe2+ (DETC), complex. EGb 761 inhibited the forma tion of TEARS, the release of CK, and mitigated the incidence of ventr icular arrhythmias in a dose dependent way. Both L-arginine and SOD in creased the signal intensity of NOFe2+ (DETC)(2) complex and inhibited the formation of TEARS, the leakage of CK and the incidence of ventri cular arrythmia. NNA not only had no protective effects on myocardial injury, but also increased the incidence of reperfusion-induced arrhyt hima, 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. (C) 1998 Elsevier Science B.V. All rights reserved.