title: Different effects of dronedarone and amiodarone on pulmonary vein electrophysiology, mechanical properties and H2O2-induced arrhythmogenicity.
abstract: Dronedarone and amiodarone are anti-atrial fibrillation agents with different potency. Pulmonary veins play a critical role in the genesis of atrial fibrillation. Oxidative stress can enhance pulmonary vein arrhythmogenesis. This study was done to compare the effects of dronedarone and amiodarone on pulmonary vein electrophysiological and mechanical properties, and oxidative stress-induced arrhythmogenecity. Conventional microelectrodes were used to record action potentials in isolated rabbit pulmonary vein specimens before and after dronedarone and amiodarone with or without the presence of H2O2 (2mM). Dronedarone (0.1, 1 and 10 μM) concentration-dependently decreased pulmonary vein beating rates (from 2.2±0.1 to 1.9±0.1, 1.8±0.1 and 1.7±0.1Hz, n=8, P<0.01). Amiodarone (0.1, 1 and 10 μM) also concentration-dependent decreased pulmonary vein beating rates (from 2.5±0.2 to 2.3±0.2, 2.2±0.2 and 2.0±0.2Hz, n=7, P<0.01). However, dronedarone decreased pulmonary vein beating rates to a greater extent at 0.1 μM (12% versus 4%, P<0.005) and 1μM (17% versus 9%, P<0.005). Dronedarone or amiodarone (0.1, 1 and 10 μM) did not change the pulmonary vein contractility. However, dronedarone (1 and 10 μM) concentration-dependent reduced pulmonary vein diastolic tension by 13±2 mg (P<0.005) and 18±3 mg (P<0.005). In contrast, amiodarone did not change pulmonary vein diastolic tension. Dronedarone (10 μM) and amiodarone (10 μM) attenuated H2O2-induced pulmonary vein burst firings from 100% to 33.3% (P<0.01), and to 0% (P<0.005), respectively. In conclusion, amiodarone and dronedarone both significantly reduced pulmonary vein spontaneous beating rates and H2O2-induced pulmonary vein arrhythmogenesis. However, only dronedarone produced pulmonary vein vasodilation.
authors: Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan.
authors: Dicky Armein
authors: DA
authors: Hanafy
authors: Yao-Chang
authors: YC
authors: Chen
authors: Shih-Lin
authors: SL
authors: Chang
authors: Yen-Yu
authors: YY
authors: Lu
authors: Yung-Kuo
authors: YK
authors: Lin
authors: Yu-Hsun
authors: YH
authors: Kao
authors: Shih-Ann
authors: SA
authors: Chen
authors: Yi-Jen
authors: YJ
authors: Chen
mesh_terms: D000638:Amiodarone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D000077764:Dronedarone; D055724:Electrophysiological Phenomena; D006861:Hydrogen Peroxide; D066298:In Vitro Techniques; D018384:Oxidative Stress; D011667:Pulmonary Veins / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits
chemical_list: D000889:Anti-Arrhythmia Agents; D006861:Hydrogen Peroxide; D000077764:Dronedarone; D000638:Amiodarone