Abstract
BACKGROUND: Dronedarone is approved by the U.S. Food and Drug Administration for the treatment of patients with atrial fibrillation (AF) as a safe alternative to amiodarone. There are no full-length published reports describing the effectiveness of acute dronedarone use against AF in experimental or clinical studies. OBJECTIVE: The purpose of this study was to determine the effect of acute dronedarone and amiodarone on electrophysiological parameters, and their anti-AF efficacy in canine isolated arterially perfused right atria. METHODS: Transmembrane action potentials and pseudoelectrocardiograms were recorded. Acetylcholine (ACh, 1.0 muM) was used to induce persistent AF. RESULTS: Amiodarone-induced changes were much more pronounced than those of dronedarone on (1) action potential duration (DeltaAPD(90), +51 +/- 17 ms vs. 4 +/- 6 ms, P >.01), (2) effective refractory period (DeltaERP, +84 +/- 23 ms vs. 18 +/- 9 ms, P <.001), (3) diastolic threshold of excitation (DeltaDTE, +0.32 +/- 0.11 mA vs. 0.03 +/- 0.02 mA, P <.001), and (4) V(max) (DeltaV(max), -43 +/- 14% vs. -11 +/- 4%, P <.01, n = 5 to 6; all recorded at 10 muM, cycle length = 500 ms). Persistent AF was induced in 10 of 10 atria exposed to ACh alone; subsequent addition of dronedarone or amiodarone terminated AF in 1 of 7 and 4 of 5 atria, respectively. Persistent ACh-mediated AF was induced in 5 of 6 and 0 of 5 atria pretreated with dronedarone and amiodarone, respectively. CONCLUSION: The electrophysiological effects and anti-AF efficacy of acute dronedarone are much weaker than those of amiodarone in a canine model of AF. The efficacy of acute dronedarone to prevent induction of acetylcholine-mediated AF as well as to terminate persistent AF in canine right atria is relatively poor. Our data suggest that acute dronedarone is a poor substitute for amiodarone for acute cardioversion of AF or prevention of AF recurrence.