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J Am Coll Cardiol, 2007; 50:1505-1512, doi:10.1016/j.jacc.2007.05.046 (Published online 21 September 2007).
© 2007 by the American College of Cardiology Foundation
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PRECLINICAL STUDY

Reduced Incidence of Vagally Induced Atrial Fibrillation and Expression Levels of Connexins by n-3 Polyunsaturated Fatty Acids in Dogs

Jean-Francois Sarrazin, MD*, Genevieve Comeau, MSc*, Pascal Daleau, PhD*,{dagger}, John Kingma, PhD*,{ddagger}, Isabelle Plante, PhD*, Dominique Fournier, MSc* and Franck Molin, MD*,{ddagger},*

* Institut Universitaire de Cardiologie et Pneumologie, Quebec, Canada
{dagger} Faculty of Pharmacy, Laval University, Quebec, Canada
{ddagger} Faculty of Medicine, Laval University, Quebec, Canada.

Manuscript received February 14, 2007; revised manuscript received April 30, 2007, accepted May 1, 2007.

* Reprint requests and correspondence: Dr. Franck Molin, Institut Universitaire de Cardiologie et Pneumologie, 2725, Chemin Sainte Foy, Quebec, G1V 4G5 Canada. (Email: franck.molin{at}med.ulaval.ca).

Objectives: This open-label canine study assessed whether n-3 polyunsaturated fatty acids (PUFAs) prevent vagally induced atrial fibrillation (AF) and influence atrial tissue expression levels of connexins (CXs).

Background: n-3 polyunsaturated fatty acids in fish oils protect against sudden cardiac death and reduce postoperative AF. Changes in spatial organization of gap junctions or cellular CX levels have been linked to arrhythmogenesis.

Methods: Vagally induced AF was studied. Eight dogs were given fish oil daily for 14 days. Eight control dogs had reproducibly induced AF and were re-evaluated after intravenous administration of fish oil. Atrial fibrillation was compared, and n-3 PUFA, CX40, and CX43 protein levels were assessed in atrial biopsies.

Results: Atrial tissue n-3 PUFA levels increased in oral treatment dogs (5.78 ± 0.71% vs. 2.49 ± 0.46% in control animals, p < 0.001). No difference was observed for atrial refractory periods or hemodynamic or electrocardiographic parameters. Incidence of AF in oral treatment dogs decreased 79% with the extra stimulus technique (10.5% vs. 48.9%, p = 0.003) and 42% with burst induction (22.5% vs. 38.8%, p = 0.038). Both CX40 and CX43 levels were lower in oral treatment dogs (60% [p = 0.019] and 42% [p = 0.038] lower, respectively); protection against AF was mostly related to reduced CX40 expression levels (p = 0.02). In dogs that were given intravenous n-3 PUFAs, AF inducibility by the extra stimulus technique was reduced from 75.0% to 28.6% (p = 0.002).

Conclusions: Oral treatment with fish oils increased atrial n-3 PUFA levels and reduced vulnerability to induction of AF in this dog model. Modulation of cardiac CX by n-3 PUFAs probably contributes to the antiarrhythmic effects of fish oils.

Abbreviations and Acronyms
  AF = atrial fibrillation
  BCL = basic cycle length
  CX = connexin
  DHA = docosahexaenoic acid
  EPA = eicosapentaenoic acid
  ERP = effective refractory period
  HR = heart rate
  PAC = premature atrial complex
  PUFA = polyunsaturated fatty acid


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