Kohro S, Hogan Q H, Nakae Y, Yamakage M, Bosnjak Z J
Department of Anesthesiology Research, Medical College of Wisconsin, Milwaukee 53226, USA.
Anesthesiology. 2001 Dec;95(6):1435-340. doi: 10.1097/00000542-200112000-00024.
Volatile anesthetics show an ischemic preconditioning-like cardioprotective effect, whereas intravenous anesthetics have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetics on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP) channel and mitochondrial flavoprotein oxidation.
Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an indicator of mitochondrial flavoprotein oxidation, was monitored with fluorescence microscopy while myocytes were exposed individually for 15 min to isoflurane, sevoflurane, propofol, and pentobarbital. The authors further investigated the effect of 5-hydroxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and sevoflurane-induced flavoprotein oxidation. Additionally, the effects of propofol and pentobarbital on isoflurane-induced flavoprotein oxidation were measured.
Isoflurane and sevoflurane induced dose-dependent increases in flavoprotein oxidation (isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflurane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbital showed no significant effects on flavoprotein oxidation, they both dose-dependently inhibited isoflurane-induced flavoprotein oxidation.
Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism contributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, but the administration of propofol or pentobarbital may potentially inhibit the cardioprotective effect of inhalational anesthetics.
挥发性麻醉药显示出类似缺血预处理的心脏保护作用，而静脉麻醉药对缺血再灌注损伤具有心脏保护作用。尽管最近的证据表明线粒体三磷酸腺苷调节钾（mitoK(ATP)）通道在心脏预处理中很重要，但麻醉药对mitoK(ATP)的影响尚未得到研究。因此，作者检验了麻醉药作用于mitoK(ATP)通道和线粒体黄素蛋白氧化的假设。
从成年豚鼠中分离心肌细胞。在心肌细胞分别暴露于异氟烷、七氟烷、丙泊酚和戊巴比妥15分钟时，用荧光显微镜监测内源性线粒体黄素蛋白荧光，这是线粒体黄素蛋白氧化的一个指标。作者进一步研究了5-羟基癸酸（一种特异性mitoK(ATP)通道拮抗剂）对异氟烷和七氟烷诱导的黄素蛋白氧化的影响。此外，还测量了丙泊酚和戊巴比妥对异氟烷诱导的黄素蛋白氧化的影响。
异氟烷和七氟烷诱导黄素蛋白氧化呈剂量依赖性增加（异氟烷：R2 = 0.71，n = 50；七氟烷：R2 = 0.86，n = 20）。5-羟基癸酸消除了异氟烷和七氟烷产生的荧光增加。尽管丙泊酚和戊巴比妥对黄素蛋白氧化没有显著影响，但它们都呈剂量依赖性抑制异氟烷诱导的黄素蛋白氧化。
吸入麻醉药通过打开mitoK(ATP)通道诱导黄素蛋白氧化。这可能是导致麻醉诱导预处理的一个重要机制。静脉麻醉药的心脏保护作用可能不依赖于黄素蛋白氧化，但丙泊酚或戊巴比妥的给药可能会潜在地抑制吸入麻醉药的心脏保护作用。
