d,l-Sotalol reverses abbreviated atrial refractoriness and prevents promotion of atrial fibrillation in a canine model with left ventricular dysfunction induced by atrial tachypacing

Circ J. 2009 Oct;73(10):1820-8. doi: 10.1253/circj.cj-09-0321. Epub 2009 Aug 27.

Abstract

Background: This study evaluated antiarrhythmic effects of d,l-sotalol in a canine atrial fibrillation (AF) model with left ventricular dysfunction.

Methods and results: Thirteen beagles (Sotalol group n=7 and Control group n=6) were subjected to atrial tachypacing (ATP) (400 beats/min) with intact atrioventricular conduction for 4 weeks. Oral d,l-sotalol (2 mg/kg) was administered 1 week after starting ATP and continued throughout the experiment. One week after starting ATP, atrial effective refractory periods (AERPs) were shortened in both groups. However, d,l-sotalol treatment gradually prolonged AERP, resulting in a significant prolongation of AERP compared with the Control group at 4 weeks (Control 76 +/-4 and Sotalol 126 +/-5 ms, p<0.01). d,l-Sotalol treatment showed lower AF inducibility and shorter AF duration at 4 weeks. In the control group, expressions of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA were downregulated by 46.2% and 43.0%, respectively, after 4 weeks of ATP; d,l-sotalol treatment did not affect these changes.

Conclusions: d,l-Sotalol treatment prolonged AERP, even after atrial electrical remodeling had developed, and prevented AF perpetuation without affecting downregulated expression of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA in an ATP-induced canine AF model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Administration, Oral
  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / pharmacology*
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / genetics
  • Atrial Fibrillation / pathology
  • Atrial Fibrillation / physiopathology
  • Atrial Fibrillation / prevention & control*
  • Atrial Function / drug effects*
  • Calcium Channels, L-Type / genetics
  • Cardiac Pacing, Artificial
  • Disease Models, Animal
  • Dogs
  • Down-Regulation
  • Echocardiography
  • Electrocardiography
  • Electrophysiologic Techniques, Cardiac
  • Fibrosis
  • Heart Atria / drug effects
  • Heart Atria / physiopathology
  • RNA, Messenger / metabolism
  • Shal Potassium Channels / genetics
  • Sotalol / administration & dosage
  • Sotalol / pharmacology*
  • Time Factors
  • Ventricular Dysfunction, Left / drug therapy*
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / genetics
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left

Substances

  • Adrenergic beta-Antagonists
  • Anti-Arrhythmia Agents
  • Calcium Channels, L-Type
  • L-type calcium channel alpha(1C)
  • RNA, Messenger
  • Shal Potassium Channels
  • Sotalol