挥发性麻醉药对大鼠离体心脏缺血再灌注损伤的影响

Effects of volatile anesthetics on rat heart ischemia-reperfusion injury in vitro

目的:研究挥发性麻醉药对大鼠离体心脏缺血再灌注损伤的影响。方法:SD大鼠136只,随机分为17组,每组8只。采用Langendorff离体大鼠心脏模型。按给药方式分为6大组:假手术组(含1亚组):自然灌流85 min;对照组(含4亚组):平衡15 min为1亚组,平衡后续灌15 min为1亚组,平衡续灌后缺血10 min为1亚组,平衡续灌缺血25 min后复灌30 min为1亚组;氟烷组(含3亚组):平衡15 min后,灌注含1.5 MAC氟烷灌注液15 min为1亚组,平衡续灌含药液后缺血10 min为1亚组,平衡续灌缺血25 min复灌含1.5 MAC氟烷的灌注液30 min为1亚组;1.5 MAC的恩氟烷、异氟烷、七氟烷大组,各大组包括3亚组,处理同氟烷组。记录各组心脏在平衡15 min、给药后(或续灌15 min)、复灌30min的左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室发展压(LVDP)、左室压力升高或降低最大速率(±dp/dtmax)、心率(HR)、冠脉流量(CF)。实验结束后测定心肌超氧化物歧化酶(SOD)活性、心肌丙二醛(MDA)含量、高能磷酸盐(ATP)含量、Na+-K+-ATP酶、Ca2+-ATP酶活性。结果:(1)恩氟烷、异氟烷、七氟烷组在给药后CF高于对照组(P<0.05);各用药组在给药后LVDP、±dp/dtmax低于对照组(P<0.01)、而LVEDP高于对照组(P<0.05);复灌30 min各用药组LVDP、±dp/dtmax高于对照组(P<0.01)。氟烷、异氟烷组在给药后和复灌30 min的HR低于对照组(P<0.05或P<0.01)。(2)各用药组在缺血前、缺血期和复灌30 min的心肌ATP含量高于及复灌30 min SOD活性高于对照组,MDA含量低于对照组(P<0.05或P<0.01)。(3)氟烷、恩氟烷、异氟烷组在缺血前Ca2+-ATP酶活性低于对照组、各用药组在缺血期和复灌30 min此酶活性高于对照组(P<0.05或P<0.01)。(4)在复灌30min,氟烷组的Na+-K+-ATP酶活性高于对照组和其它3用药组(P<0.05或P<0.01)。结论:挥发性麻醉药可抑制心肌收缩功能,对缺血再灌注心肌有保护作用。缺血再灌注后,能明显促进心肌功能与代谢的恢复,而且能提高CF、心肌Ca2+-ATP酶及Na+-K+-ATP酶活性。

AIM： To investigate the effect of volatile anesthetics on function, metabolism, ATPase activity and free radicals in isolated ischemia/reperfusion （I/R） rat hearts. METHODS： 136 SD rats were anesthetized with pentobarbital and randomly divided into six groups and 17 sub - groups （ n = 8 ） , according to the given drug. In a normal thermal isolated Langendorff rat heart model, four volatile anesthetics in 1.5 MAC concentration were given before global ischemia 25 min and during reperfusion 30 min. Coronary flow （ CF）, LVEDP, left ventricular developed pressure （ LVDP）, ± dp/dt were monitored at 15 min of equilibrium, 15 min of drug treatment, the end of reperfusion. Myocardial adenosine triphosphate （ ATP）, malodialdehyde （ MDA）, activity of Ca^＋2 - ATPase and Na^＋ - K ^＋ - ATPase, and superoxide dismutase （SOD） were determined at 15 min of equilibrium, 15 min of drug treatment or absence, 10 min global ischemia and the end of reperfusion. RESULTS： CF and LVEDP were increased significantly after exposured to volatile anesthetics 15 min, and LVDP, ＋ dp/dtmax were significantly decreased. However, LVDP and ＋ dp/dtmax were increased at the end of reperfusion in the treated groups. HR in halothane and isoflurane groups was decreased before ischemia and after reperfu-sion. The myocardial ATP content was significantly increased before and after ischemia in the treated groups. At the end of reperfusion, the activity of SOD was significantly higher and myocardial MDA content was significantly lower in the treated groups than those in control group. The activity of Ca^＋2 - ATPase, compared with the control group, was markedly decreased before ischemia in halothane, enflurane and isoflurane group. Nonetheless, the activity of Ca^2＋ - ATPase was clearly increased in the treated groups during ischemia and at the end of reperfusion. The activity of Na^＋ - K ^＋ - ATPase was only enhanced in halothane group at the end of reperfusion among groups. CONCLUSION ： The volatile anesthetics depress myocardial systolic function. There are markedly protective effects against myocardial I/R injury. Meanwhile, the volatile anesthetics improve the recovery of function and metabolism, and increase CF and the activity of Ca^＋2 - ATPase and Na^＋ - K ^＋ - ATPase in rats.