Ismaeil M S, Tkachenko I, Hickey R F, Cason B A
Department of Anesthesia, University of California-San Francisco, USA.
Anesthesiology. 1999 Dec;91(6):1816-22. doi: 10.1097/00000542-199912000-00036.
When administered before prolonged myocardial ischemia and reperfusion, isoflurane exerts potent cardioprotective effects similar to those inferred by ischemic preconditioning. To determine whether an intact cytoskeleton is critically important in isoflurane-induced preconditioning, the authors used a rabbit model in which isoflurane-induced myocardial preconditioning decreases myocardial infarct size (IS) substantially. In this model, the authors tested whether the microtubule depolymerizing agent, colchicine, would inhibit isoflurane-induced myocardial preconditioning.
Myocardial IS was measured in four 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 only the control group received no pretreatment. An isoflurane-preconditioned group was pretreated with 15 min of end-tidal isoflurane, 1.1%, and then 15 min of washout. An isoflurane-plus-colchicine group was administered 2 mg/kg colchicine intravenously before isoflurane pretreatment. A colchicine-control group was administered 2 mg/kg colchicine but no isoflurane pretreatment. Myocardial IS and area at risk (AR) were defined by staining. Data were analyzed by analysis of variance or covariance.
Infarct size, expressed as a percentage of AR (IS:AR) was 33.6%+/-8.8% (SD) in the control group. Isoflurane preexposure reduced myocardial IS:AR significantly, to 11.8%+/-9.1%. Colchicine pretreatment eliminated the preconditioning-like effect of isoflurane (IS:AR = 32.6%+/-8.7%). Colchicine alone did not alter IS (IS:AR = 27.6%+/-7.1%; P = not significant).
Colchicine abolished the preconditioning effect of isoflurane but did not increase IS when administered alone. An intact microtubular cytoskeleton is critically important in the process of volatile anesthetic-induced preconditioning.
在长时间心肌缺血和再灌注之前给予异氟烷，其发挥的强大心脏保护作用类似于缺血预处理所产生的保护作用。为了确定完整的细胞骨架在异氟烷诱导的预处理中是否至关重要，作者使用了一种兔模型，在该模型中，异氟烷诱导的心肌预处理可显著减小心肌梗死面积（IS）。在这个模型中，作者测试了微管解聚剂秋水仙碱是否会抑制异氟烷诱导的心肌预处理。
在四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。各组仅在预处理方面有所不同，且只有对照组未接受预处理。异氟烷预处理组用1.1%的呼气末异氟烷预处理15分钟，然后冲洗15分钟。异氟烷加秋水仙碱组在异氟烷预处理前静脉注射2mg/kg秋水仙碱。秋水仙碱对照组给予2mg/kg秋水仙碱，但未进行异氟烷预处理。通过染色确定心肌梗死面积和危险区域（AR）。数据采用方差分析或协方差分析。
梗死面积以AR的百分比表示（IS:AR），对照组为33.6%±8.8%（标准差）。异氟烷预暴露显著降低心肌IS:AR，降至11.8%±9.1%。秋水仙碱预处理消除了异氟烷的预处理样效应（IS:AR = 32.6%±8.7%）。单独使用秋水仙碱未改变梗死面积（IS:AR = 27.6%±7.1%；P无显著性差异）。
秋水仙碱消除了异氟烷的预处理效应，但单独使用时并未增加梗死面积。完整的微管细胞骨架在挥发性麻醉剂诱导的预处理过程中至关重要。
