Atrial-selective effects of chronic amiodarone in the management of atrial fibrillation.
BACKGROUND
Although amiodarone is one of the most effective pharmacologic agents used in clinical management of atrial fibrillation (AF), little is known about its differential effects in atrial and ventricular myocardium.


OBJECTIVE
This study sought to compare the electrophysiological effects of chronic amiodarone in atria and ventricles.


METHODS
We compared the electrophysiological characteristics of coronary-perfused atrial and ventricular wedge preparations isolated from untreated and chronic amiodarone-treated dogs (amiodarone, 40 mg/kg/day for 6 weeks, n = 12).


RESULTS
Chronic amiodarone prolonged action potential duration (APD(90)) predominantly in atria compared to ventricles and prolonged the effective refractory period (ERP) more than APD(90) in both ventricular and atrial preparations (particularly in the latter) due to the development of postrepolarization refractoriness. Amiodarone reduced dispersion of APD(90) in both atria and ventricles. Although the maximum rate of increase of the action potential upstroke (V(max)) was significantly lower in both atria and ventricles of amiodarone-treated hearts versus untreated controls, the reduction of V(max) was much more pronounced in atria. Amiodarone prolonged P-wave duration more significantly than QRS duration, reflecting greater slowing of conduction in atria versus ventricles. These atrioventricular distinctions were significantly accentuated at faster activation rates. Persistent acetylcholine-mediated AF could be induced in only 1 of 6 atria from amiodarone-treated versus 10 of 10 untreated dogs.


CONCLUSIONS
Our results indicate that under the conditions studied, chronic amiodarone has potent atrial-predominant effects to depress sodium channel-mediated parameters and that this action of the drug is greatly potentiated by its ability to prolong APD predominantly in the atria, thus contributing to its effectiveness to suppress AF.
Burashnikov
Alexander
A
Masonic Medical Research Laboratory, Utica, New York 13501, USA.
Di Diego
José M
JM
Sicouri
Serge
S
Ferreiro
Marcela
M
Carlsson
Leif
L
Antzelevitch
Charles
C
D000284:Administration, Oral; D000638:Amiodarone / Q000008:administration & dosage*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D016275:Atrial Function / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005500:Follow-Up Studies; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone