Dexmedetomidine preconditioning attenuates myocardial ischemia/reperfusion-induced arrhythmia in rats by inhibiting KATP channels via imidazoline receptors: A combined animal and in vitro study.

BACKGROUND: Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, could decrease the incidence of arrhythmias after cardiac surgery. However, the precise mechanisms underlying DEX's modulation of arrhythmic cardiac electrophysiology require further elucidation.

METHODS: We used myocardial ischemia/reperfusion model in vivo to examine the effects of DEX on antiarrhythmic, and papillary muscle and single ventricular myocytes in vitro to explore the electrophysiological effect of dexmedetomidine by using whole-cell patch clamp recording technique.

RESULT: In vivo experiment, DEX significantly decreased the arrhythmia score and increased left ventricular systolic pressure during the 30 min of ischemia and 120 min of reperfusion. In vitro experiment, DEX prolonged action potential duration (APD) 50 and APD 90, and decreased the ATP sensitive potassium current (IKATP) in a dose-dependent manner. Yohimbine, an antagonist of α2 receptors, had no effect on the inhibition of DEX on IKATP, while pretreatment with idazoxan, an imidazoline I1 receptors antagonist, could change the effect of DEX on IKATP in cardiac myocytes.

CONCLUSIONS: The present study demonstrates that dexmedetomidine exerts antiarrhythmic effects, which are associated with the suppression of sarcolemmal KATP channel function and moderate prolongation of APD. Pharmacological evidence using receptor antagonists suggests that this novel action is likely mediated through imidazoline I1 receptor signaling rather than the classical α2-adrenoceptor pathway.