Ginkgo biloba extract (EGb 761) improves postischemic function in isolated preconditioned working rat hearts.
BACKGROUND
We studied the effect of preconditioning and Gikgo biloba extract (EGb 761) in relation to the recovery of contractile function after global ischemia in the isolated working rat heart.


METHODS
Hearts (n = 12 in each group) were randomly divided into five groups: In group I, hearts were subjected to 30 min of normothermic global ischemia followed by 30 min of reperfusion; in group II, they were subjected to one cycle of preconditioning consisting of 5 min ischemia and 10 min reperfusion before the induction of 30 min of ischemia and 30 min of reperfusion; group III hearts underwent two cycles of preconditioning; group IV hearts underwent three cycles of preconditioning; and group hearts underwent four cycles of preconditioning before the onset of 30 min ischemia followed by 30 min of reperfusion.


RESULTS
Ventricular fibrillation (total) and ventricular tachycardia (no preconditioning) both fell from 100% to 50% (P < 0.05) after four cycles of preconditioning. In relation to ventricular fibrillation, preconditioning significantly reduced the formation of oxygen free radicals, measured by electron spin resonance spectroscopy (ESR), but recovery of cardiac function was low in all preconditioned groups. Because of the relatively low incidence of arrhythmias (50% ventricular fibrillation and 50% ventricular tachycardia) and relatively low cardiac function in Group V, EGb 761, a free-radical scavenger, was chosen to improve myocardial contractile function in preconditioned hearts. Fifty and 100 mg/kg of EGb 761 (per os) significantly improved coronary flow, aortic flow, left ventricular developed pressure (LVDP), and the first derivative of LVDP (LVDdP/dtmax) 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 761 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 formation of free radicals was reduced by approximately 50 and 60% using 50 mg/kg and 100 mg/kg of EGb 761, respectively, when compared with the four-cycle preconditioned drug-free control group.


CONCLUSIONS
We have demonstrated that EGb 761 can improve contractile function after global ischemia in the isolated working rat heart by reducing the formation of oxygen free radicals, and we have shown that this protection is additive to that of ischemia-induced preconditioning.
Tosaki
A
A
University of Connecticut Health Center, Farmington 06030-1110.
Engelman
D T
DT
Pali
T
T
Engelman
R M
RM
Droy-Lefaix
M T
MT
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D020441:Ginkgo biloba; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000737:chemistry; D010477:Perfusion; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis; D017180:Tachycardia, Ventricular / Q000517:prevention & control; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000517:prevention & control; D000096983:Ginkgo Extract
D016166:Free Radical Scavengers; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract