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.

中文翻译：

---

促进炎症消退的干预措施可预防左心室功能障碍引起的心房颤动


目的 最近的研究表明，称为消退素的生物活性介质可促进炎症的主动消退。炎症信号传导参与心房颤动 (AF) 基质的形成。评估 resolvin-D1 对大鼠心肌梗死 (MI) 引起的左心室功能障碍引起的房性心律失常重构的影响。方法和结果 MI 通过结扎左冠状动脉前降支产生。干预组每天接受腹膜内 Resolvin-D1，从 MI 手术前（早期 RvD1）或 MI 后第 7 天（晚期 RvD1）开始，一直持续到 MI 后第 21 天。通过电生理学研究评估 AF 脆弱性。通过光学测绘分析心房传导。通过马森三色染色对纤维化进行量化；通过 qPCR 和 RNA 测序进行基因表达。调查人员对群体身份视而不见。 Early-RvD1 显着降低了 MI 大小（17 ± 6%，而媒介物 MI 为 39 ± 6%）并保留了左心室射血分数；这些不受晚期 RvD1 的影响。经食管起搏引起房性快速心律失常的假手术大鼠为 2/18 (11%)，相比之下，仅接受 MI 的大鼠为 18/18 (100%)，早期 RvD1 MI 大鼠为 5/18（28%，P < 0.001 与 MI） -大鼠和 7/12 (58%, P < 0.01) 晚期 RvD1 MI 大鼠。心梗后心房传导速度显着降低； RvD1 治疗可抑制这种效应。早期和晚期 RvD1 均限制了 MI 诱导的心房纤维化，并阻止 MI 诱导的炎症和纤维化相关生物标志物和通路的心房表达增加。结论 RvD1 抑制 MI 相关的房性心律失常重构。 早期RvD1具有MI保留和心房重塑抑制作用，而晚期RvD1在没有心室保护的情况下减弱心房重塑和AF促进，揭示了与心室功能变化无关的心房保护作用。这些结果表明，促进炎症消退的化合物是一种新型心脏保护干预措施，尤其对减弱房颤底物的发展感兴趣。