Effects of Antiarrhythmic Drugs on Fibrillation in the Remodeled Atrium

• Kaori Shinagawa

  From the Research Center and Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.

• Akiko Shiroshita-Takeshita

  From the Research Center and Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.

• Gernot Schram

  From the Research Center and Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.

• Stanley Nattel

  From the Research Center and Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.

書誌事項

タイトル別名

• Insights Into the Mechanism of the Superior Efficacy of Amiodarone

抄録

Background— The basis of the unique effectiveness of amiodarone for atrial fibrillation (AF) is poorly understood. The present study tested the hypothesis that amiodarone blocks electrical remodeling induced by atrial tachycardia. Methods and Results— Mongrel dogs were subjected to atrial tachycardia (400 bpm for 7 days) in the absence and presence of therapy with amiodarone, the class III cardiac antiarrhythmic drug dofetilide, or the class I agent flecainide begun 3 days before the onset of tachypacing and maintained until a final electrophysiological study. AF vulnerability (percentage of sites with AF induction by single premature extrastimuli), mean AF duration, atrial effective refractory period (ERP), and conduction velocity were compared among these dogs and in unpaced dogs in the absence or presence of treatment with the same agents. Only amiodarone prevented promotion of AF duration and vulnerability by atrial tachycardia. Furthermore, only amiodarone eliminated tachycardia-induced ERP abbreviation and loss of ERP rate adaptation while obviating L-type Ca 2+ -current α 1c -subunit downregulation as determined by Western blot. In an additional series of dogs monitored with repeated electrophysiological studies, amiodarone administered after the induction of atrial tachycardia remodeling reversed remodeling within several days, despite continued atrial tachypacing during amiodarone therapy. Conclusions— Amiodarone is uniquely effective against AF promotion by atrial tachycardia remodeling in this experimental model and prevents electrophysiological and biochemical consequences of remodeling. Amiodarone also reversed remodeling established by 4 days of atrial tachycardia. The inhibition of atrial tachycardia remodeling may therefore contribute to the superior efficacy of amiodarone in AF.

収録刊行物

• Circulation

  Circulation 107 (10), 1440-1446, 2003-03-18

  Ovid Technologies (Wolters Kluwer Health)

キーワード

• Physiology (medical)
• Cardiology and Cardiovascular Medicine

詳細情報

• CRID: 1364233270179559680
• NII論文ID: 30022668295
• DOI: 10.1161/01.cir.0000055316.35552.74
• ISSN: 15244539
• ISSN: 00097322
• Web Site: https://www.ahajournals.org/doi/full/10.1161/01.CIR.0000055316.35552.74
• データソース種別:
  • Crossref
  • CiNii Articles