Ginkgo biloba extract (EGb 761) pretreatment limits free radical-induced oxidative stress in patients undergoing coronary bypass surgery.
A growing body of evidence supports the trigger role of free radicals in the delayed functional and metabolic myocardial recovery following cardiopulmonary bypass (CPB) in humans, thus opening the field to specific therapies. This clinical study was designed to evaluate, in 15 patients undergoing aortic valve replacement, whether the extent of CPB- and reperfusion-induced lipid peroxidation, ascorbate depletion, tissue necrosis, and cardiac dysfunction is reduced by orally administered EGb 761, a Ginkgo biloba extract with potent in vitro antiradical properties. Patients received either EGb 761 (Tanakan, 320 mg/day, n = 8) or a matching placebo (n = 7) for 5 days before surgical intervention. Plasma samples were obtained from the peripheral circulation and the coronary sinus at crucial stages of the operation (i.e., before incision, during ischemia, and within the first 30 minutes post-unclamping), and up to 8 days postoperatively. Upon aortic unclamping, EGb 761 inhibited the transcardiac release of thiobarbituric acid-reactive species (p < 0.05), as assessed by high-performance liquid chromatography, and attenuated the early (5-10 minute) decrease in dimethylsulfoxide/ascorbyl free radical levels, an electron spin resonance index of the plasma ascorbate pool (p < 0.05). EGb 761 also significantly reduced the more delayed leakage of myoglobin (p = 0.007) and had an almost significant effect on ventricular myosin leakage (p = 0.053, 6 days postoperatively). The clinical outcome of recovery of treated patients was improved, but not significantly, compared with untreated patients. Our results demonstrate the usefulness of adjuvant EGb 761 therapy in limiting oxidative stress in cardiovascular surgery and suggest the possible role of highly bioavailable terpene constituents of the drug.
Pietri
S
S
Structure et Réactivité des Espèces Paramagnétiques, CNRS URA 1412, Université de Provence, Marseille, France.
Séguin
J R
JR
d'Arbigny
P
P
Drieu
K
K
Culcasi
M
M
D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000097:blood / Q000378:metabolism; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005609:Free Radicals; D020441:Ginkgo biloba; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010936:Plant Extracts / Q000627:therapeutic use*; D011292:Premedication; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000096983:Ginkgo Extract
D001205:Ascorbic Acid; D016166:Free Radical Scavengers; D005609:Free Radicals; D008315:Malondialdehyde; D010936:Plant Extracts; D017392:Thiobarbituric Acid Reactive Substances; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract