N-3 Polyunsaturated Fatty Acids Prevents Atrial Fibrillation By Inhibiting Inflammation And Oxidative Stress In A Canine Sterile Pericarditis Model

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Since the incidence of coronary artery disease (CAD) of the Eskimo is just one-tenth of the Scandinavian has been awared of in the 1980s, more and more attention have been paid to the cardiovascular effect of dietary n-3 polyunsaturated fatty acids from fish oil supplementation. Evidence has been accumulating regarding the role of n-3 polyunsaturated fatty acids (PUFAs) in the prevention and management of cardiovascular disease (CVD). The cardio-protenctive effect of PUFAs supplementation includes beneficial effect for treatment of CAD, hypertension and hypercholesterolaemia. Consumption of the long chain omega-3 fatty acids are associated reduce the cardiac mortality in post myocardial infarction patients and presumably ventricular tachyarrhythmia. However, population studies testing the hypothesis that n-3 PUFAs can prevent AF have demonstrated conflicting results. Our study focus the PUFAs anti-inflammtory and anti-oxidative stress properties to evaluate the antiarrhythmic effects in a canine sterile pericarditis model, and give a new evidence and strategy for AF prevention.Objective: It has been recently reported that atrial fibrillation (AF) is associated with tissue inflammation and Inflammatory cytokines. N-3 polyunsaturated fatty acids (PUFAs) have been reported anti-inflammatory effects in some epidemiological studies. However, the anti-inflammatory effect of PUFAs on AF is unclear. The purpose of the present study was to evaluate the anti-inflammatory effect and anti-oxidative stress properties of PUFAs on AF in a canine sterile pericarditis model.Methods: 20 dogs randomly assigned to two groups: a control group (10 dogs) and a PUFAs treatment group (10 dogs), which were created a sterile pericarditis by open-chest operation. PUFAs was administered orally (2 g/ day) beginning 4 week before the operation until the end of the study. Before and 2 days after the operation, CRP, IL-6, IL-1?, TNF-?levels, the inducibility and maintenance of AF, the atrial effective refractory period (AERPs), and intra-atrial conduction time were determined. And the 3-nitrotyrosine content of atrial tissue were determined.Results: Before the operation, there were no significant differences in any of the parameters between the two groups. On the second postoperative day, the PUFAs group had a lower CRP level (7.6±0.5 vs. 11.7±1.3 mg/dl, P<0.0001), a lower IL-6 level(202.9±23.8 vs. 242.0±19.6 pg/ml, P<0.0001), a lower TNF-?level(83.3±8.5 vs. 112.4±8.2 pg/ml, P<0.0001), a less AF inducibility (percentage of burst attempts leading to AF episodes: 11±7.4 vs. 28±10.3, P<0.001) and maintenance [median AF duration: 1105s(655.8~1406.5) vs. 2516.5s(1187~3361), P <0.05], a longer AERP (133.4±4.1 vs. 129.8±4.3 ms, P<0.05), and a shorter intra-atrial conduction time (46.6±4.4 vs. 51.9±4.8 ms, P<0.05) than the control group. The 3-nitrotyrosine content of atrial tissue in PUFAs group is significantly lower compared with control group(P<0.0001).Conclusions: Dietary n-3 PUFAs supplementation attenuates the inducibility and maintenance of AF in an animal model of sterile pericarditis. Depression of proinflammatory cytokines and oxidative stress by n-3 PUFAs probably contributes to the antiarrhythmic effects.