Pietri S, Séguin J R, d'Arbigny P, Drieu K, Culcasi M
Structure et Réactivité des Espèces Paramagnétiques, CNRS URA 1412, Université de Provence, Marseille, France.
Cardiovasc Drugs Ther. 1997 Apr;11(2):121-31. doi: 10.1023/a:1007728729844.
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.
越来越多的证据支持自由基在人类体外循环（CPB）后心肌功能和代谢延迟恢复中所起的触发作用，从而为特定治疗开辟了领域。本临床研究旨在评估，对于15例接受主动脉瓣置换术的患者，口服EGb 761（一种具有强大体外抗自由基特性的银杏叶提取物）是否能减少CPB和再灌注诱导的脂质过氧化、抗坏血酸消耗、组织坏死以及心脏功能障碍的程度。患者在手术干预前5天接受EGb 761（达纳康，320毫克/天，n = 8）或匹配的安慰剂（n = 7）。在手术的关键阶段（即切开前、缺血期间和松开主动脉夹后的前30分钟）以及术后长达8天，从外周循环和冠状窦采集血浆样本。松开主动脉夹时，通过高效液相色谱法评估，EGb 761抑制了硫代巴比妥酸反应性物质的经心释放（p < 0.05），并减弱了二甲基亚砜/抗坏血酸自由基水平的早期（5 - 10分钟）下降，这是血浆抗坏血酸池的电子自旋共振指标（p < 0.05）。EGb 761还显著减少了肌红蛋白更延迟的泄漏（p = 0.007），并且对心室肌球蛋白泄漏有几乎显著的影响（p = 0.053，术后6天）。与未治疗的患者相比，治疗患者的恢复临床结果有所改善，但不显著。我们的结果证明了辅助使用EGb 761疗法在限制心血管手术中的氧化应激方面的有用性，并提示了该药物中高生物利用度萜类成分可能发挥的作用。
