An inflammation resolution-promoting intervention prevents atrial fibrillation due to left-ventricular dysfunction.

AIMS: Recent studies suggest that bioactive mediators called resolvins promote active resolution of inflammation. Inflammatory signaling is involved in development of the substrate for atrial fibrillation (AF). To evaluate effects of resolvin-D1 on atrial arrhythmogenic remodeling resulting from left-ventricular dysfunction induced by myocardial infarction (MI) in rats.

METHODS AND RESULTS: MI was produced by left anterior descending coronary-artery ligation. Intervention-groups received daily intraperitoneal resolvin-D1, beginning before MI-surgery (early-RvD1) or day-7 post-MI (late-RvD1) and continued until day-21 post-MI. AF-vulnerability was evaluated by electrophysiological study. Atrial conduction was analyzed by optical mapping. Fibrosis was quantified by Masson's trichrome staining; gene-expression by qPCR and RNA-sequencing. Investigators were blinded to group identity.Early-RvD1 significantly reduced MI-size (17 ± 6%, vs. 39 ± 6% in vehicle-MI) and preserved left-ventricular ejection fraction; these were unaffected by late-RvD1. Transesophageal pacing induced atrial tachyarrhythmia in 2/18 (11%) sham-operated rats, vs. 18/18 (100%) MI-only rats, 5/18 (28%, P < 0.001 vs. MI) early-RvD1 MI-rats and 7/12 (58%, P < 0.01) late-RvD1 MI rats. Atrial conduction velocity significantly decreased post-MI; an effect suppressed by RvD1-treatment. Both early- and late-RvD1 limited MI-induced atrial fibrosis and prevented MI-induced increases in atrial expression of inflammation- and fibrosis-related biomarkers and pathways.

CONCLUSIONS: RvD1 suppressed MI-related atrial arrhythmogenic remodeling. Early-RvD1 had MI-sparing and atrial-remodeling suppressant effects, whereas late-RvD1 attenuated atrial remodeling and AF-promotion without ventricular protection, revealing atrial-protective actions unrelated to ventricular-function changes. These results point to inflammation-resolution promoting compounds as novel cardioprotective interventions with particular interest in attenuating AF-substrate development.