氟烷、异氟醚和恩氟烷对缺血再灌注心肌的保护作用

目的:研究氟烷、异氟醚和恩氟烷对缺血再灌注心肌功能、代谢自由基的影响。方法:SD大鼠104只,随机数字表法分为13小组,每组8只。采用Langendorff离体大鼠心脏模型。按给药方式又分为对照、氟烷、恩氟烷、异氟醚4大组。①对照组(含4小组):平衡15 min组,平衡后续灌15 min组,平衡续灌后缺血10min组,平衡续灌缺血25 min后复灌30 min组。②氟烷组(含3小组):平衡15 min后,灌注含1.5肺泡气最低有效浓度(minimal alveolar concentration,MAC)氟烷灌注液15min组,平衡续灌后缺血10 min组,平衡续灌缺血25 min复灌含1.5MAC氟烷的灌注液30 min组。③恩氟烷和异氟醚组,各包括3小组,情况同氟烷组。各组记录平衡后,给药(或续灌15 min)复灌30 min左心室收缩压、左心室舒张末期压(left ventricular diastolicpressure,LVEDP)、左心室发展压、左心室压力升高或降低最大速率、心率、冠状动脉流量(coronary flow,CF)。实验结束后测定心肌超氧化物歧化酶(superoxide dismutase,SOD)活性、心肌丙二醛含量、高能磷酸盐(ATP)含量。结果:①恩氟烷、异氟醚具有明显扩张冠状动脉的作用。恩氟烷能促进缺血再灌注心肌冠脉流量的恢复。②各用药组明显降低左心室发展压、左心室压力升高速率,升高LVEDP(各P<0.05);缺血再灌注后,氟烷、恩氟烷、异氟醚组的左心室发展压分别恢复到基础值的57%,62%,59%(均P<0.01),左心室压力升高速率分别恢复到基础值的56%,67%,74%(均P<0.01);与对照组恢复的左心室发展压(27%)、左心室压力升高速率(13%)相比,具有差异非常显著性意义(各P<0.01)。③各用药组均能提高心肌ATP含量,缺血后心肌ATP下降较慢,复灌后恢复较快。④复灌后用药组SOD活性较高;丙二醛生成量下降(P<0.05)。结论:三种挥发性麻醉药对心肌收缩功能具有一定的抑制作用。缺血再灌注后,能明显促进心肌功能与代谢的恢复,而且能提高冠脉流量、SOD酶活性。提示这些作用可能是挥发性麻醉药抗心肌缺血再灌注损伤机制之一。

Protective effects of halothane and enflurane and isoflurane on ischemia-reperfusion myocardial

Objective: To investigate the effect halothane and enflurane and isofluraneon function,metabolism and ATPase activity in isolated ischemia/reperfusion(I/R) rat hearts.Methods: 104 SD rats were anesthetized with 3% pentobarbital 30 mg.kg~(-1),it were randomly divided into 13 little groups(n=8),or 4 big groups according to given drug.In a normal thermal isolated langendorff rat heart model,three volatile anesthetics in 1.5MAC concentration were given before global ischemia and after reperfusion.4 big groups were studied.Group Ⅰ (contain 4 little groups,control group) received 30 min of perfusion and then 25 min of ischemia followed 30 min of reperfusion.All the treatment groups(group Ⅱ:1.5MAC halothane;group Ⅲ:1.5MAC enflurane;group Ⅳ:1.5MAC isoflurane) received 15 min of perfusion and 15 min of drug treatment followed by 25 min of ischemia and 30 min of reperfusion. Every big group contain3 little groups. A latex balloon was placed in the left ventricle to obtain isovolumetric contraction. Coronary flow (CF),left ventricular diastolic pressure (LVEDP),left ventricular developed pressure (LVDP),+dp/dt and -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 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: 15 min treatment with volatile anesthetics resulted in a significant decrease in LVDP, + dp/dt. CF was increased significantly after exposure to enflurane and isoflurane but not halothane. Also the myocardial ATP content were significantly increased after exposure to anesthetics. After 10 min ischemia the myocardial ATP content decreased slowly in treated groups. At the end of reperfusion, ventricular function, CF, myocardial ATP content and the activity of SOD in the treated groups were significantly higher than those in control group. Myocardial MDA content in treated groups was significantly lower than those in the control group. Conclusion: The volatile anesthetics depressed myocardial systolic function in normal myocardium. During ischemia period, the volatile anesthetics decreased the extent of ischemia contracture. During reperfusion period, the volatile anesthetics improved the recovery of function and metabolism, and increased CF and the activity SOD. These results indicated that it may be one of mechanism against ischemia reperfusion injury.