Ismaeil M S, Tkachenko I, Gamperl A K, Hickey R F, Cason B A
Department of Anesthesiology, University of California, San Francisco and the Veterans Affairs Medical Center, 94121, USA.
Anesthesiology. 1999 Mar;90(3):812-21. doi: 10.1097/00000542-199903000-00024.
Isoflurane has cardioprotective effects that mimic the ischemic preconditioning phenomenon. Because adenosine triphosphate-sensitive potassium channels and adenosine receptors are implicated in ischemic preconditioning, the authors wanted to determine whether the preconditioning effect of isoflurane is mediated through these pathways.
Myocardial infarct size was measured in seven groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed only in the pretreatments given, and controls received no pretreatment. An ischemia-preconditioned group was pretreated with 5 min of coronary occlusion and 15 min of reperfusion. An isoflurane-preconditioned group was pretreated with 15 min end-tidal isoflurane, 1.1%, and then 15 min of washout. An isoflurane-plus-glyburide group was administered 0.33 mg/kg glyburide intravenously before isoflurane pretreatment. An isoflurane plus 8-(p-sulfophenyl)-theophylline (SPT) group received 7.5 mg/kg SPT intravenously before isoflurane. Additional groups were administered identical doses of glyburide or SPT, but they were not pretreated with isoflurane. Infarct size and area at risk were defined by staining. Data were analyzed by analysis of variance or covariance.
Infarct size, expressed as a percentage of the area at risk (IS:AR) was 30.2+/-11% (SD) in controls. Ischemic preconditioning and isoflurane preexposure reduced myocardial infarct size significantly, to 8.3+/-5% and 13.4+/-8.2% (P<0.05), respectively. Both glyburide and SPT pretreatment eliminated the preconditioning-like effect of isoflurane (IS:AR = 30.0+/-9.1% and 29.2+/-12.6%, respectively; P = not significant). Neither glyburide nor SPF alone increased infarct size (IS:AR = 33.9+/-7.6% and 31.8+/-12.7%, respectively; P = not significant).
Glyburide and SPT abolished the preconditioning-like effects of isoflurane but did not increase infarct size when administered in the absence of isoflurane. Isoflurane-induced preconditioning and ischemia-induced preconditioning share similar mechanisms, which include activation of adenosine triphosphate-sensitive potassium channels and adenosine receptors.
异氟烷具有类似缺血预处理现象的心脏保护作用。由于三磷酸腺苷敏感性钾通道和腺苷受体与缺血预处理有关，作者想要确定异氟烷的预处理效应是否通过这些途径介导。
在七组丙泊酚麻醉的兔中测量心肌梗死面积，每组均经历30分钟的前外侧冠状动脉闭塞，随后再灌注3小时。各组仅在预处理上有所不同，对照组未接受预处理。一个缺血预处理组接受5分钟的冠状动脉闭塞和15分钟的再灌注预处理。一个异氟烷预处理组接受15分钟的呼气末异氟烷（浓度1.1%）预处理，然后冲洗15分钟。一个异氟烷加格列本脲组在异氟烷预处理前静脉注射0.33mg/kg格列本脲。一个异氟烷加8-（对-磺基苯基）-茶碱（SPT）组在异氟烷预处理前静脉注射7.5mg/kg SPT。其他组给予相同剂量的格列本脲或SPT，但未用异氟烷预处理。梗死面积和危险区域通过染色确定。数据通过方差分析或协方差分析进行分析。
梗死面积以危险区域面积的百分比表示（IS:AR），对照组为30.2±11%（标准差）。缺血预处理和异氟烷预处理显著减小了心肌梗死面积，分别降至8.3±5%和13.4±8.2%（P<0.05）。格列本脲和SPT预处理均消除了异氟烷的类似预处理效应（IS:AR分别为30.0±9.1%和29.2±12.6%；P无统计学意义）。单独使用格列本脲或SPF均未增加梗死面积（IS:AR分别为33.9±7.6%和31.8±12.7%；P无统计学意义）。
格列本脲和SPT消除了异氟烷的类似预处理效应，但在无异氟烷时给药不会增加梗死面积。异氟烷诱导的预处理和缺血诱导的预处理具有相似的机制，包括三磷酸腺苷敏感性钾通道和腺苷受体的激活。
