Atrial fibrillation (AF) is the most common type of arrhythmia encountered clinically. AF risk factors include hypertension, respiratory diseases, obesity, or heart failure. Right heart disease (RHD) has also been described among AF risk factors associated with an atrial inflammatory profile leading to AF. Studies focusing on the cardiomyocytes (CM) orchestration of the tri-factorial relation between RHD, inflammation, and AF are rare. This project aims to characterize the proarrhythmogenic remodeling affecting atrial cardiomyocyte in a rat model of RHD induced by permanent pulmonary trunk constriction.

Characterize RHD induced electrophysiological and morphological CM remodeling leading to atrial inflammation and fibrosis, responsible for increased AF susceptibility.

Pulmonary artery banding (PAB) was performed on Wistar rats weighing 225–275g to induce right-sided cardiac hypertrophy and dilation. Sham animals did not receive the PAB surgery. Cardiac echography and electrophysiological studies were performed in vivo on all animals before sacrifice, 21 days post-surgery. Optical mapping was performed ex-vivo on Langendorff-perfused hearts. Freshly isolated right ventricular (RV), as well as right and left atrial (RA and LA) CM, underwent contractility recording in vitro. Histological analyses were performed to assess myocardial fibrosis and Connexin-43 levels. Genes and protein levels were obtained by qPCR and Western-blot analyses respectively.

PAB animals developed severe ventricular and atrial myocardial hypertrophy and dilation compared to Sham, as assessed by echocardiography. PAB animals were significantly more susceptible to AF compared to Sham. Freshly isolated CM revealed that overall CM size was increased in PAB animals, and contractile activity of CM was increased compared to the Sham rats. Analyses of targeted protein and gene expression levels by immunohistochemistry and qPCR analyses showed enhanced expression of fibrosis and inflammation-related compounds in whole-RA and RA CM from PAB, compared to Sham.

RHD induces electro-physiological remodeling influencing the RA CM contractile machinery which in turn, leads to the development of pro-arrhythmogenic substrate including atrial inflammation, fibrosis, and enhanced AF inducibility.