Dexmedetomidine inhibited arrhythmia susceptibility to adrenergic stress in RyR2 R2474S mice through regulating the coupling of membrane potential and intracellular calcium

Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, can decrease the incidence of arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the underlying mechanisms by which DEX affects cardiac electrophysiological function remain unclear. Ryanodine receptor (RyR2) heterozygous R2474S mice were used as a model for CPVT. WT and RyR2 mice were treated with isoproterenol (ISO) and DEX, and electrocardiograms were continuously monitored during both in vivo and ex vivo experiments. Dual-dye optical mapping was used to explore the anti-arrhythmic mechanism of DEX. DEX significantly reduced the occurrence and duration of ISO-induced of VT/VF in RyR2 mice in vivo and ex vivo. DEX remarkably prolonged action potential duration (APD ) and calcium transient duration (CaTD ) in both RyR2 and WT hearts, whereas it reduced APD heterogeneity and CaT alternans in RyR2 hearts. DEX inhibited ectopy and reentry formation, and stabilized voltage-calcium latency. DEX exhibited an antiarrhythmic effect through stabilizing membrane voltage and intracellular Ca . DEX can be used as a beneficial perioperative anesthetic for patients with CPVT or other tachy-arrhythmias.