Omega-3 polyunsaturated fatty acids prevent atrial fibrillation associated with heart failure but not atrial tachycardia remodeling

Background - There is epidemiological evidence that omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of atrial fibrillation (AF), but clinical data are conflicting. The present study assessed the effects of PUFA on AF in experimental models. Methods and Results - We studied the effects of oral PUFA supplements in 2 experimental AF paradigms: electrical remodeling induced by atrial tachypacing ( 400 bpm for 1 week) and congestive heart failure - associated structural remodeling induced by ventricular tachypacing ( 240 bpm for 2 weeks). PUFA pretreatment did not directly change atrial effective refractory period (128 +/- 6 [mean +/- SEM] versus 127 +/- 2 ms; all effective refractory periods at 300-ms cycle lengths) or burst pacing - induced AF duration (5 +/- 4 versus 34 +/- 18 seconds). Atrial tachypacing dogs had shorter refractory periods (73 +/- 6 ms) and greater AF duration (1185 +/- 300 seconds) than shams (119 +/- 5 ms and 20 +/- 11 seconds; P < 0.01 for each). PUFAs did not significantly alter atrial tachypacing effects on refractory periods (77 +/- 8 ms) or AF duration (1128 +/- 412 seconds). PUFAs suppressed ventricular tachypacing - induced increases in AF duration (952 +/- 221 versus 318 +/- 249 seconds; P < 0.05) and attenuated congestive heart failure - related atrial fibrosis (from 19.2 +/- 1.1% to 5.8 +/- 1.0%; P < 0.001) and conduction abnormalities. PUFAs also attenuated ventricular tachypacing - induced hemodynamic dysfunction (eg, left ventricular end-diastolic and left atrial pressure from 12.2 +/- 0.5 and 11.4 +/- 0.6 mm Hg, respectively, to 6.4 +/- 0.5 and 7.0 +/- 0.8 mm Hg; P < 0.01) and phosphorylation of mitogen-activated protein kinases (extracellular-signal related and P38 kinase). Conclusions - PUFAs suppress congestive heart failure - induced atrial structural remodeling and AF promotion but do not affect atrial tachycardia - induced electrical remodeling. The beneficial effects of PUFAs on structural remodeling, possibly related to prevention of mitogen-activated protein kinase activation, may contribute to their clinical anti-AF potential.