Tanaka Katsuya, Weihrauch Dorothee, Kehl Franz, Ludwig Lynda M, LaDisa John F, Kersten Judy R, Pagel Paul S, Warltier David C
Department of Anesthesiology, Pharmacology and Toxicology, the Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Anesthesiology. 2002 Dec;97(6):1485-90. doi: 10.1097/00000542-200212000-00021.
Reactive oxygen species (ROS) contribute to myocardial protection during ischemic preconditioning, but the role of the ROS in protection against ischemic injury produced by volatile anesthetics has only recently been explored. We tested the hypothesis that ROS mediate isoflurane-induced preconditioning in vivo.
Pentobarbital-anesthetized rabbits were instrumented for measurement of hemodynamics and were subjected to a 30 min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive vehicle (0.9% saline), or the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2-mercaptopropionyl glycine (2-MPG; 1 mg. kg(-1).min(-1)), in the presence or absence of 1.0 minimum alveolar concentration (MAC) isoflurane. Isoflurane was administered for 30 min and then discontinued 15 min before coronary artery occlusion. A fluorescent probe for superoxide anion production (dihydroethidium, 2 mg) was administered in the absence of the volatile anesthetic or 5 min before exposure to isoflurane in 2 additional groups (n = 8). Myocardial infarct size and superoxide anion production were assessed using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively.
Isoflurane (P < 0.05) decreased infarct size to 24 +/- 4% (mean +/- SEM; n = 10) of the left ventricular area at risk compared with control experiments (43 +/- 3%; n = 8). NAC (43 +/- 3%; n = 7) and 2-MPG (42 +/- 5%; n = 8) abolished this beneficial effect, but had no effect on myocardial infarct size (47 +/- 3%; n = 8 and 46 +/- 3; n = 7, respectively) when administered alone. Isoflurane increased superoxide anion production as compared with control experiments (28 +/- 12 -6 +/- 9 fluorescence units; P < 0.05).
The results indicate that ROS produced following administration of isoflurane contribute to protection against myocardial infarction in vivo.
活性氧（ROS）在缺血预处理期间有助于心肌保护，但ROS在防止挥发性麻醉剂引起的缺血性损伤中的作用直到最近才被探索。我们检验了ROS介导异氟烷体内预处理的假说。
用戊巴比妥麻醉的兔子安装用于测量血流动力学的仪器，然后进行30分钟冠状动脉闭塞，随后再灌注3小时。兔子被随机分配接受载体（0.9%生理盐水），或ROS清除剂N-乙酰半胱氨酸（NAC；150mg/kg）或N-2-巯基丙酰甘氨酸（2-MPG；1mg·kg⁻¹·min⁻¹），在有或没有1.0最低肺泡浓度（MAC）异氟烷的情况下。异氟烷给药30分钟，然后在冠状动脉闭塞前15分钟停药。在另外两组（n = 8）中，在没有挥发性麻醉剂的情况下或在暴露于异氟烷前5分钟给予用于检测超氧阴离子产生的荧光探针（二氢乙锭，2mg）。分别使用三苯基四氮唑染色和共聚焦荧光显微镜评估心肌梗死面积和超氧阴离子产生。
与对照实验（43±3%；n = 8）相比，异氟烷（P < 0.05）将梗死面积降低至左心室危险区域面积的24±4%（平均值±标准误；n = 10）。NAC（43±3%；n = 7）和2-MPG（42±5%；n = 8）消除了这种有益作用，但单独给药时对心肌梗死面积没有影响（分别为47±3%；n = 8和46±3；n = 7）。与对照实验相比，异氟烷增加了超氧阴离子的产生（28±12 - 6±9荧光单位；P < 0.05）。
结果表明，异氟烷给药后产生的ROS有助于体内抗心肌梗死保护。
