不同剂量氯胺酮对大鼠离体缺血再灌注损伤心肌8-异前列腺素水平的影响

Effects of different doses of ketamine on 8-isoprostane in isolated rat hearts after myocardial ischemia-reperfusion

目的比较不同剂量氯胺酮对大鼠离体缺血再灌注损伤心肌8-异前列腺素的影响。方法成年Wistar大鼠24只,随机均分为心肌缺血再灌注(IR)组、5μmol/L氯胺酮(KL)组、10μmol/L氯胺酮(KM)组和50μmol/L氯胺酮(KH)组。四组首先采用Langendorff逆灌装置建立离体心脏缺血再灌注模型,以K-H液平衡灌注10 min后,再分别应用不含氯胺酮、含5μmol/L、10μmol/L和50μmol/L氯胺酮的K-H液灌注10 min,之后全心停灌25 min,复灌30 min。测定冠状动脉流出液中总乳酸脱氢酶(LDH)、心尖部心肌组织8-异前列腺素和超氧化物歧化酶(SOD)含量,并取左心室心肌组织观察超微结构变化。结果与IR组比较,KL和KM组8-异前列腺素、SOD及LDH含量均无统计学差异(P>0.05),超微结构变化也未见损伤减轻;KH组8-异前列腺素和LDH含量明显升高(P<0.05),超微结构损伤加重。结论 5μmol/L和10μmol/L氯胺酮对大鼠离体心肌缺血再灌注损伤和8-异前列腺素含量无明显影响,而50μmol/L氯胺酮则增加8-异前列腺素含量、加重心肌损伤。

Objective To compare the effects of three different doses of ketamine on 8-isoprostane in isolated rat hearts after myocardial ischemia-reperfusion.Methods Twenty-four adult Wistar rats weighing 240-300 g were randomly divided into 4 groups(n=6 each):ischemia-reperfusion group(I/R group),5 μmol/L ketamine group(KL),10 μmol/L ketamine group(KM),50 μmol/L ketamine group(KH).The isolated myocardial ischemia-reperfusion models were prepared with Langendorff perfusion system.The rat hearts were initially perfused with Krebs-Henseleit(K-H)solution for 10 min,and then respectively perfused with K-H solution contained no ketamine,5 μmol/L ketamine,10 μmol/L ketamine,50 μmol/L ketamine for 10 min followed by 25 min global ischemia and 30 min reperfusion.The total lactate dehydrogenase(LDH)in the reperfusion K-H solution,levels of 8-isoprostane and SOD activity of tissue samples from apex of hearts were evaluated.The tissues from left ventricular were used for observing myocardial ultrastructure.Results Levels of 8-isoprostane,LDH and SOD activity in group KL and KM did not significantly differ from I/R group(P>0.05).The microscopic examination also showed that two doses ketamine cannot alleviate the myocardial I/R injury.While compared with I/R group,levels of 8-isoprostane and LDH were increased significantly(P<0.05),the myocardial ultrastructure was injuried more severely.Conclusions Ketamine(5,10 μmol/L)cannot decrease the levels of 8-isoprostane or suppress myocardial ischemia-reperfusion injury.Ketamine(50 μmol/L)aggravate lipid peroxidation and myocardial ischemia-reperfusion injury.