Eicosapentaenoic acid prevents atrial fibrillation associated with heart failure in a rabbit

23 Atrial fibrillation (AF) is associated with morbidity and mortality of heart failure. 24 Eicosapentaenoic acid (EPA), which is contained in fish oil, was shown to reduce risk of 25 cardiovascular diseases. We investigated the effects of EPA on AF associated with heart failure in 26 a rabbit model. Rabbits were subjected to ventricular tachypacing (VTP) for 4 weeks with or 27 without EPA treatment. Continuous VTP induced heart failure status in these rabbits. The 28 duration of AF (DAF) induced by burst pacing was analyzed by electrophysiological studies. 29 VTP resulted in increased DAF following burst pacing. EPA treatment attenuated increased DAF. 30 Atrial fibrosis increased in response to VTP, accompanied by extracellular signal-regulated 31 kinase (ERK) phosphorylation and transforming growth factor-beta1 (TGF-β1) expression in the 32 atrium. Treatment with EPA attenuated atrial fibrosis, ERK phosphorylation, and TGF-β1 33 expression in response to VTP. EPA treatment increased adiponectin as an anti-inflammatory 34 adipokine and decreased tumor necrosis factor alpha as a pro-inflammatory adipokine in the 35 atrium and epicardial adipose tissues. EPA attenuated VTP-induced AF promotion and atrial 36 remodeling, which was accompanied by modulating the profiles of adipokine production from 37 epicardial adipose tissue. EPA may be useful for prevention and treatment of AF associated with 38 heart failure. 39 40