Montreal Heart Institute.
Montreal Heart Institute; Department of Pharmacology and Physiology, Université de Montréal.
J Vis Exp. 2024 Aug 30(210). doi: 10.3791/67001.
Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA). Recent studies have shown that RV and RA inflammation plays an important role in the arrhythmogenesis of CA, including AF. However, the impact of inflammation in the development of CA and AF in RHF is poorly described. Experimental models of RHF are required to better understand the association between right-sided myocardial inflammation and CA. The rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH) is well-established to provoke RHF. However, MCT triggers severe pneumo-toxicity and pulmonary inflammation. Hence, MCT-induced RHF does not help to distinguish whether the subsequent myocardial inflammation originates from the RHF per se or circulating inflammatory signals secreted by the injured lung. In this article, a mechanical method involving pulmonary artery trunk banding (PAB) was used to provoke right-sided cardiac arrhythmogenesis. The PAB consists of performing a permanent suture of the pulmonary artery trunk for 3 weeks. Such an approach generates increased right-sided pressure overload. At D21 post-PAB, the suture results in hypertrophied, dilated, and inflamed RV and RA. The PAB-induced RHF is also accompanied by vulnerability to ventricular and atrial arrhythmias, including AF.
临床状况，包括慢性阻塞性肺疾病或肺动脉高压（PAH），可导致慢性右心室压力过载和进行性右心衰竭（RHF）。RHF 可通过右侧心脏肥大和扩张以及异常心肌功能来识别，这会影响 RV 和右心房（RA）。我们最近证明，严重的 RHF 伴随着心房炎症、心房纤维化和心房颤动（AF）的风险增加，AF 是最常见的心律失常（CA）类型。最近的研究表明，RV 和 RA 炎症在 CA 的心律失常发生中起着重要作用，包括 AF。然而，炎症在 RHF 中 CA 和 AF 的发展中的影响描述得还不够充分。需要 RHF 的实验模型来更好地理解右侧心肌炎症与 CA 之间的关系。利用单硝酸戊四醇酯（MCT）诱导的肺动脉高压（PH）的大鼠模型是诱发 RHF 的成熟模型。然而，MCT 会引发严重的肺毒性和肺炎症。因此，MCT 诱导的 RHF 并不能帮助区分随后的心肌炎症是源自 RHF 本身还是源自受损肺部分泌的循环炎症信号。在本文中，一种涉及肺动脉主干结扎（PAB）的机械方法被用于引发右侧心脏心律失常的发生。PAB 包括对肺动脉主干进行 3 周的永久性缝合。这种方法会导致右心压力过载增加。在 PAB 后第 21 天，缝合会导致 RV 和 RA 肥大、扩张和炎症。PAB 诱导的 RHF 还伴随着心室和心房心律失常（包括 AF）的易感性增加。
