Abstract
Aim:
To investigate the potential of propofol in suppressing ventricular arrhythmias and to examine whether mitochondrial ATP-sensitive potassium channels are involved.
Methods:
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 KATP 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.
Results:
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.
Conclusion:
Propofol preconditioning suppresses ischemia-induced ventricular arrhythmias in the rat heart, which are proposed to be caused by opening of mitochondrial KATP channels.
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Acknowledgements
We thank Dr Tom XU from Toledo University, USA, for kindly polishing the language of this manuscript. The funding for this study is partly granted by National 973 Project (No 2007CB512008), the National Scientific Fund of China (No 30901392), Shanghai Jiao Tong University School of Medicine Scientific Research Fund, and the Shanghai First People's Hospital Scientific Fund (No 11B24).
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Liu, Q., Yao, Jy., Qian, C. et al. Effects of propofol on ischemia-induced ventricular arrhythmias and mitochondrial ATP-sensitive potassium channels. Acta Pharmacol Sin 33, 1495–1501 (2012). https://doi.org/10.1038/aps.2012.86
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DOI: https://doi.org/10.1038/aps.2012.86
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