Copyright © 2007, European Society of Cardiology
The pharmacological response of ischemia-related atrial fibrillation in dogs: Evidence for substrate-specific efficacy
aResearch Center and Departments of Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Canada
bResearch Center and Department of Pathology, Montreal Heart Institute and Université de Montréal, Montreal, Canada
* Corresponding author. 5000 Belanger Street East, Montreal, Quebec H1T 1C8, Canada. Tel.: +1 514 376 3330; fax: +1 514 376 1355. Email address: stanley.nattel{at}icm-mhi.org
Objective: Acute atrial ischemia produces a substrate for atrial fibrillation (AF) maintenance, but the response of this substrate to antiarrhythmic-drugs has not been defined. The present study assessed the effects of class 1–4 antiarrhythmic-drugs on the electrophysiological consequences of acute atrial ischemia, and compared effects in ischemic AF with those in vagal AF.
Methods and results: Isolated atrial ischemia was created by ligating a right coronary artery branch perfusing the right atrial free wall. Experiments were performed in dogs treated with loading and maintenance doses of flecainide (class 1; n=5), nadolol (class 2, n=7), dofetilide (class 3, n=5), or diltiazem (class 4, n=7) prior to coronary artery occlusion. Dogs subjected to coronary occlusion without pre-treatment (n=10) served as controls. Coronary artery occlusion substantially increased AF duration, e.g. from 7±4 s (pre-ischemic baseline) to 876±245 s at 3 h of ischemia, and caused substantial ischemic zone conduction slowing. Diltiazem and nadolol prevented AF promotion (AF durations 12±8 s and 4±1 s at 3 h of ischemia respectively; each p<0.001 vs control) and suppressed ischemic conduction slowing. Flecainide and dofetilide failed to prevent ischemia-induced AF promotion (e.g. AF duration at 3-hour ischemia 779±417 and 801±414 respectively, p=NS vs control) and failed to alter ischemia-induced conduction slowing. A different pattern of response occurred with vagal AF: flecainide was highly effective in reducing vagal AF duration; dofetilide, diltiazem, and nadolol were ineffective.
Conclusions: Beta-blockade and Ca2+ antagonism suppress the arrhythmic consequences of acute atrial ischemia, whereas Na+ channel or K+-channel block are ineffective. These results are relevant to understanding the effects of different classes of antiarrhythmic-drugs on AF occurring in coronary disease patients.
KEYWORDS Arrhythmia; Antiarrhythmic agents; Conduction (block); Ischemia
Time for primary review 27 days
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