Department of Cardiology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Acta Pharmacol Sin. 2012 Dec;33(12):1495-501. doi: 10.1038/aps.2012.86. Epub 2012 Sep 17.
To investigate the potential of propofol in suppressing ventricular arrhythmias and to examine whether mitochondrial ATP-sensitive potassium channels are involved.
Male Sprague-Dawley rats were pretreated with intravenous infusion of propofol (Prop), a selective mitochondrial KATP channel inhibitor 5-hydroxydecanoate (5-HD), propofol plus 5-HD (Prop+5-HD), a potent mitochondrial K(ATP) channel opener diazoxide (DZ) or NS, respectively. The dosage of each drug was 10 mg/kg. The animals then underwent a 30 min-ligation of the left anterior descending artery. The severity of arrhythmias, the incidence of ventricular fibrillation (VF), and the time of the first run of ventricular arrhythmias were documented using an arrhythmia scoring system. Mitochondrial membrane potential (ΔΨm) was measured in freshly isolated rat cardiomyocytes with a fluorescence microscope.
The arrhythmia scores in the Prop and DZ group were 2.6(0-5) and 2.4(0-5), respectively, which were significantly lower than that in the control group [4.9(2-8)]. VF was not observed in both Prop and DZ groups. The first run of ventricular arrhythmias was significantly postponed in the Prop group (10.5±2.2 vs 7.3±1.9 min). Bracketing of propofol with 5-HD eliminated the anti-arrhythmic effect of propofol. In isolated rat cardiomyocytes, propofol (50 μmol/L) significantly decreased ΔΨm, but when propofol was co-administered with 5-HD, the effect on ΔΨm was reversed.
Propofol preconditioning suppresses ischemia-induced ventricular arrhythmias in the rat heart, which are proposed to be caused by opening of mitochondrial K(ATP) channels.
探讨异丙酚抑制室性心律失常的作用及其与线粒体三磷酸腺苷敏感性钾通道的关系。
雄性 Sprague-Dawley 大鼠静脉输注异丙酚（Prop）、线粒体 ATP 敏感性钾通道抑制剂 5-羟癸酸（5-HD）、异丙酚加 5-HD（Prop+5-HD）、线粒体 K（ATP）通道开放剂二氮嗪（DZ）或 NS 预处理，剂量均为 10mg/kg。随后结扎左前降支 30min。采用心律失常评分系统记录心律失常严重程度、室颤（VF）发生率和首次室性心律失常发作时间。用荧光显微镜测量新鲜分离的大鼠心肌细胞中线粒体膜电位（ΔΨm）。
Prop 组和 DZ 组的心律失常评分分别为 2.6（0-5）和 2.4（0-5），显著低于对照组[4.9（2-8）]。Prop 组和 DZ 组均未发生 VF。Prop 组首次室性心律失常发作明显延迟[10.5±2.2min 比 7.3±1.9min]。用 5-HD 阻断异丙酚后，异丙酚的抗心律失常作用被消除。在分离的大鼠心肌细胞中，异丙酚（50μmol/L）显著降低了ΔΨm，但当异丙酚与 5-HD 同时给药时，对ΔΨm 的影响则被逆转。
异丙酚预处理可抑制大鼠心脏缺血引起的室性心律失常，这可能是由于线粒体 K（ATP）通道的开放所致。
