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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^_*,, John Kingma, PhD^_*,, Isabelle Plante, PhD^_*, Dominique Fournier, MSc^_* and Franck Molin, MD^_*,,_*

^_* Institut Universitaire de Cardiologie et Pneumologie, Quebec, Canada
Faculty of Pharmacy, Laval University, Quebec, Canada
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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