Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Eur J Pharmacol. 2012 Feb 29;677(1-3):138-46. doi: 10.1016/j.ejphar.2011.12.030. Epub 2011 Dec 29.
Our previous clinical study reported that isoflurane preconditioning and high-dose propofol posttreatment attenuated myocardial ischemia/reperfusion injury of patients in surgery with cardiopulmonary bypass (CPB). This study was designed to confirm this cardiac protection by use of a dog CPB model and to elucidate the related mechanism. Adult mongrel male dogs undergoing standard CPB were assigned into 4 groups: Sham group, Propofol group, Isoflurane (Iso) group and isoflurane in combination of propofol (pre-Iso+P) group. After induction, anesthesia was maintained with propofol (Propofol group), isoflurane (Iso group) or isoflurane preconditioning in combination with propofol posttreatment (pre-Iso+P group). After 2 h cardiac arrest and CPB, aortic cross-clamping was released to allow 2 h reperfusion. The results demonstrated that joint use of isoflurane and propofol facilitated cardiac functional recovery, improved myocardial oxygen utilization and decreased cardiac enzyme release. Also, the oxidative damage caused by ischemia/reperfusion injury was remarkably attenuated. Linear regression analysis showed that cardiac function performance and oxidative stress status were inversely correlated, indicating the improved cardiac function was in closed association with the attenuation of oxidative stress. In addition, the cardiac oxygen consumption (VO(2)) was found to be significantly associated with the above cardiac function and oxidative stress parameters, suggesting VO(2) was predictive for the levels of cardiac damage and oxidative stress. Therefore, we conclude that alternative use of isoflurane and propofol confers superior cardioprotection against postischemic myocardial injury and dysfunction, and this protection was probably mediated by attenuation of cardiac oxidative damage.
我们之前的临床研究报告称,异氟烷预处理和高剂量丙泊酚后处理可减轻体外循环(CPB)患者的心肌缺血/再灌注损伤。本研究旨在通过犬 CPB 模型证实这种心脏保护作用,并阐明相关机制。接受标准 CPB 的成年杂种雄性犬分为 4 组:假手术组、丙泊酚组、异氟烷(Iso)组和异氟烷联合丙泊酚(预 Iso+P)组。诱导后,用丙泊酚(丙泊酚组)、异氟烷(Iso 组)或异氟烷预处理联合丙泊酚后处理(预 Iso+P 组)维持麻醉。心脏停搏和 CPB 2 h 后,释放主动脉夹闭以允许再灌注 2 h。结果表明,异氟烷和丙泊酚联合使用促进了心脏功能的恢复,改善了心肌氧利用,减少了心肌酶的释放。此外,缺血/再灌注损伤引起的氧化损伤明显减轻。线性回归分析表明,心脏功能表现与氧化应激状态呈负相关,表明改善的心脏功能与氧化应激的减轻密切相关。此外,还发现心脏耗氧量(VO2)与上述心脏功能和氧化应激参数显著相关,表明 VO2 可预测心脏损伤和氧化应激的水平。因此,我们得出结论,异氟烷和丙泊酚的交替使用对缺血后心肌损伤和功能障碍具有更好的心脏保护作用,这种保护可能是通过减轻心脏氧化损伤介导的。