The pharmacological response of ischemia-related atrial fibrillation in dogs: evidence for substrate-specific efficacy

Cardiovasc Res. 2007 Apr 1;74(1):104-13. doi: 10.1016/j.cardiores.2007.01.018. Epub 2007 Jan 27.


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 Ca(2+) 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Animals
  • Anti-Arrhythmia Agents / therapeutic use*
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / prevention & control*
  • Calcium Channel Blockers / therapeutic use
  • Coronary Disease / complications
  • Coronary Disease / drug therapy*
  • Diltiazem / therapeutic use
  • Dogs
  • Electric Stimulation
  • Flecainide / therapeutic use*
  • Models, Animal
  • Nadolol / therapeutic use
  • Phenethylamines / therapeutic use
  • Potassium Channel Blockers / therapeutic use
  • Refractory Period, Electrophysiological / drug effects
  • Sodium Channel Blockers / therapeutic use
  • Sulfonamides / therapeutic use
  • Vagus Nerve


  • Adrenergic beta-Antagonists
  • Anti-Arrhythmia Agents
  • Calcium Channel Blockers
  • Phenethylamines
  • Potassium Channel Blockers
  • Sodium Channel Blockers
  • Sulfonamides
  • Nadolol
  • Diltiazem
  • Flecainide
  • dofetilide