Chronic and acute effects of dronedarone on the action potential of rabbit atrial muscle preparations: comparison with amiodarone.
Dronedarone, a noniodinated derivative of amiodarone, is under evaluation as a potentially less toxic anti-arrhythmic alternative to amiodarone. The acute and chronic electrophysiologic effects of dronedarone and amiodarone were compared in isolated rabbit atrial muscle by microelectrode techniques. Four-week PO treatment with dronedarone or amiodarone increased action potential duration (APD90) (58 +/- 4 ms control versus 69 +/- 2 ms dronedarone, p < 0.01; 68 +/- 3 ms amiodarone, p < 0.01 for a 100-mg/kg/d dose) and effective refractory period (49 +/- 6 ms control versus 68 +/- 4 ms dronedarone, p < 0.01; 63 +/- 3 ms amiodarone, p < 0.01). The APD90 prolonged reverse rate-dependency. In contrast, acute superfusion with 10 microM dronedarone or amiodarone decreased APD90 (61 +/- 6 ms control versus 53 +/- 4 ms dronedarone, p < 0.05; 52 +/- 6 ms amiodarone, p < 0.05), effective refractory period (50 +/- 5 ms control versus 44 +/- 4 ms dronedarone, p < 0.05; 43 +/- 6 ms amiodarone, p < 0.05), and the maximum upstroke slope of the action potential (Vmax) (188 +/- 9 V/s control versus 182 +/- 11 V/s dronedarone p < 0.05; 182 +/- 11 V/s amiodarone, p < 0.05). Thus, chronic and acute electrophysiologic effects of dronedarone on rabbit atrial muscle are similar to those of amiodarone, suggesting a similar potential against atrial arrhythmias.
Sun
Wei
W
Cardiovascular Research Laboratory, Department of Cardiology, VA Greater Los Angeles Health Care System of West Los Angeles, and UCLA School of Medicine, 90073, USA.
Sarma
Jonnalagedda S M
JS
Singh
Bramah N
BN
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000638:Amiodarone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000737:chemistry; D016275:Atrial Function / Q000187:drug effects* / Q000502:physiology; D000077764:Dronedarone; D004334:Drug Administration Schedule; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium; D011817:Rabbits
D000889:Anti-Arrhythmia Agents; D000077764:Dronedarone; D000638:Amiodarone