Department of Medicine, Montreal Heart Institute, University of Montreal, 5000 Belanger Street, Montreal, QC HIT 1C8, Canada.
Europace. 2024 Mar 30;26(4). doi: 10.1093/europace/euae082.
Right heart disease (RHD), characterized by right ventricular (RV) and atrial (RA) hypertrophy, and cardiomyocytes' (CM) dysfunctions have been described to be associated with the incidence of atrial fibrillation (AF). Right heart disease and AF have in common, an inflammatory status, but the mechanisms relating RHD, inflammation, and AF remain unclear. We hypothesized that right heart disease generates electrophysiological and morphological remodelling affecting the CM, leading to atrial inflammation and increased AF susceptibility.
Pulmonary artery banding (PAB) was surgically performed (except for sham) on male Wistar rats (225-275 g) to provoke an RHD. Twenty-one days (D21) post-surgery, all rats underwent echocardiography and electrophysiological studies (EPS). Optical mapping was performed in situ, on Langendorff-perfused hearts. The contractility of freshly isolated CM was evaluated and recorded during 1 Hz pacing in vitro. Histological analyses were performed on formalin-fixed RA to assess myocardial fibrosis, connexin-43 levels, and CM morphology. Right atrial levels of selected genes and proteins were obtained by qPCR and Western blot, respectively. Pulmonary artery banding induced severe RHD identified by RV and RA hypertrophy. Pulmonary artery banding rats were significantly more susceptible to AF than sham. Compared to sham RA CM from PAB rats were significantly elongated and hypercontractile. Right atrial CM from PAB animals showed significant augmentation of mRNA and protein levels of pro-inflammatory interleukin (IL)-6 and IL1β. Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase-2a (SERCA2a) and junctophilin-2 were decreased in RA CM from PAB compared to sham rats.
Right heart disease-induced arrhythmogenicity may occur due to dysfunctional SERCA2a and inflammatory signalling generated from injured RA CM, which leads to an increased risk of AF.
右心疾病（RHD）的特征为右心室（RV）和心房（RA）肥大，以及心肌细胞（CM）功能障碍，已被描述与心房颤动（AF）的发生有关。右心疾病和 AF 具有共同的炎症状态，但与 RHD、炎症和 AF 相关的机制仍不清楚。我们假设右心疾病会产生影响 CM 的电生理和形态重塑，导致心房炎症和增加 AF 易感性。
对雄性 Wistar 大鼠（225-275g）进行肺动脉带（PAB）手术（除假手术外）以引发 RHD。手术后 21 天（D21），所有大鼠均接受超声心动图和电生理研究（EPS）。在 Langendorff 灌流心脏上进行原位光学映射。在体外 1Hz 起搏下评估和记录新鲜分离的 CM 的收缩性。福尔马林固定的 RA 进行组织学分析，以评估心肌纤维化、连接蛋白-43 水平和 CM 形态。通过 qPCR 和 Western blot 分别获得右心房选定基因和蛋白质的水平。肺动脉带导致 RV 和 RA 肥大的严重 RHD。与假手术相比，肺动脉带大鼠对 AF 的易感性明显增加。与假手术相比，PAB 大鼠的 RA CM 明显伸长且过度收缩。与假手术相比，PAB 动物的 RA CM 中促炎白细胞介素（IL）-6 和 IL1β的 mRNA 和蛋白水平显著增加。与假手术相比，PAB 大鼠的 RA CM 中的肌浆内质网 Ca2+-ATPase-2a（SERCA2a）和连接蛋白-2 减少。
由于受损的 RA CM 产生功能失调的 SERCA2a 和炎症信号，可能会发生由右心疾病引起的致心律失常性，从而增加 AF 的风险。
