在豚鼠心脏中，七氟醚通过调节蛋白激酶C、线粒体ATP敏感性钾通道和一氧化氮合酶来增强乙醇诱导的心脏预处理。

Sevoflurane enhances ethanol-induced cardiac preconditioning through modulation of protein kinase C, mitochondrial KATP channels, and nitric oxide synthase, in guinea pig hearts.

作者信息

Kaneda Kazuhiro, Miyamae Masami, Sugioka Shingo, Okusa Chika, Inamura Yoshitaka, Domae Naochika, Kotani Junichiro, Figueredo Vincent M

机构信息

Department of Anesthesiology, Osaka Dental University, Osaka, Japan.

出版信息

Anesth Analg. 2008 Jan;106(1):9-16, table of contents. doi: 10.1213/01.ane.0000297298.93627.36.

DOI:10.1213/01.ane.0000297298.93627.36

PMID:18165545

Abstract

BACKGROUND

Volatile anesthetics and regular ethanol consumption induce cardioprotection mimicking ischemic preconditioning. We investigated whether sevoflurane enhances ethanol preconditioning and whether inhibition of protein kinase C (PKC) and mitochondrial K(ATP) channels attenuated this enhanced cardioprotection. The effects of regular ethanol consumption on expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase were determined.

METHODS

Isolated perfused guinea pig hearts underwent 30-min global ischemia and 120-min reperfusion (

CONTROL

CTL). The ethanol group (EtOH) received 2.5% ethanol in their drinking water for 6 wk. Anesthetic preconditioning was elicited by 10-min exposure to sevoflurane (1 minimum alveolar anesthetic concentration; 2%) in ethanol (EtOH + SEVO) or nonethanol (SEVO) hearts. PKC and mitochondrial K(ATP) channels were inhibited with chelerythrine and 5-hydroxydecanoate pretreatment, respectively. Contractile recovery was assessed by monitoring of left ventricular developed and end-diastolic pressures. Infarct size was determined by triphenyltetrazolium chloride staining. Expression of iNOS and eNOS were determined by Western blot analysis.

RESULTS

After ischemia-reperfusion, hearts from the EtOH, sevoflurane (SEVO), and EtOH + SEVO groups had higher left ventricular developed pressure and lower left ventricular end-diastolic pressure compared with CTL. Infarct size was reduced in EtOH and SEVO hearts compared with CTL (27% and 23% vs 45%, respectively, P < 0.001). Sevoflurane further reduced infarct size in EtOH hearts (27% vs 15%, P < 0.001). Chelerythrine and 5-hydroxydecanoate abolished cardioprotection in both SEVO and EtOH cardioprotected hearts. iNOS expression was reduced and eNOS expression was increased in EtOH hearts.

CONCLUSIONS

Sevoflurane enhances cardiac preconditioning induced by regular EtOH consumption. This effect is mediated in part by modulation of PKC and mitochondrial K(ATP) channels, and possibly by altered modulation of NOS expression.

摘要

背景

挥发性麻醉剂和长期乙醇摄入可诱导心脏保护作用，模拟缺血预处理。我们研究了七氟醚是否能增强乙醇预处理，以及蛋白激酶C（PKC）和线粒体ATP敏感性钾通道（mitochondrial K(ATP) channels）的抑制是否会减弱这种增强的心脏保护作用。还测定了长期乙醇摄入对诱导型一氧化氮合酶（iNOS）和内皮型一氧化氮合酶（eNOS）表达的影响。

方法

将离体灌注的豚鼠心脏进行30分钟的全心缺血和120分钟的再灌注（对照组：CTL）。乙醇组（EtOH）在其饮用水中给予2.5%乙醇，持续6周。通过在乙醇处理的心脏（EtOH + SEVO）或未用乙醇处理的心脏（SEVO）中暴露于七氟醚10分钟（1个最低肺泡有效浓度；2%）来诱导麻醉预处理。分别用白屈菜红碱和5-羟基癸酸预处理抑制PKC和线粒体K(ATP)通道。通过监测左心室舒张末压和左心室收缩压来评估收缩功能恢复情况。通过氯化三苯基四氮唑染色确定梗死面积。通过蛋白质印迹分析测定iNOS和eNOS的表达。

结果

缺血再灌注后，与CTL组相比，EtOH组、七氟醚组（SEVO）和EtOH + SEVO组的心脏左心室收缩压更高，左心室舒张末压更低。与CTL组相比，EtOH组和SEVO组的心脏梗死面积减小（分别为27%和23%，而CTL组为45%，P < 0.001）。七氟醚进一步减小了EtOH组心脏的梗死面积（27%对15%，P < 0.001）。白屈菜红碱和5-羟基癸酸消除了SEVO组和EtOH组心脏的心脏保护作用。EtOH组心脏中iNOS表达降低，eNOS表达增加。