Po-02-243 impact of partial constriction of the arterial pulmonary trunk on the development of susceptibility to atrial fibrillation in rats

Atrial Fibrillation (AF) is the most frequent and clinically important form of cardiac arrhythmia. It has been demonstrated that cardiovascular comorbidities such as myocarditis, myocardial infarction, obesity, or pulmonary hypertension (PH) promote cardiac remodeling associated with the development of atrial arrhythmogenic substrates. Right-heart disease (RHD), characterized by chronic right-sided cardiac structural and functional anomalies, has also been designated among AF risk factors. Inflammation is one of the common denominators between cardiovascular risk factors and AF vulnerability. However, no study has described the progression of the molecular and cellular changes involved in the causal link relating RHD, the activation of atrial inflammation, and the development of AF substrate. This study aims to establish the characterization of the progression of atrial arrhythmogenic inflammation in a rat model of RHD. Hypothesis Permanent constriction of the pulmonary artery trunk (PAT) provokes severe RHD associated with progressive atrial inflammation and fibrosis responsible for enhanced AF vulnerability. Pulmonary Artery Banding (PAB) reducing the PAT diameter to 1 mm, was surgically performed on 225-275g Wistar rats to induce permanent PH and severe RHD. Sham animals received PAB-mimicking intervention without ligation. Echocardiography and electrophysiological studies (EPS) were performed in vivo, on all the animals at Day0, Day7, Day14 and Day21 post-surgery. The atrial tissues were analyzed by optical mapping, histology (Masson's Trichrome), qPCR and immunoblotting. Within three weeks, PAB rats developed severe right heart remodeling characterized by progressive ventricular and atrial hypertrophy and dilation. Right atrial (RA) optical mapping revealed a reduction in conduction velocity and refractory periods in PAB rats compared to Sham. PAB rats were more vulnerable to AF than Sham starting at 7th-day until the 21st-day post-surgery. Histological analysis shows that since the 14th day until the 21st-day post-surgery RA fibrosis significantly increased in PAB rats compared to sham. Quantitative polymerase chain reaction performed on inflammation and fibrosis-related genes such as IL6, Tgfb1 or Col1a1 revealed a progressive aggravation of RA inflammatory and fibrotic status in PAB rats from Day7, Day14 to Day2 Severe RHD is associated with progressive and unresolved RA inflammation and fibrosis provoking an aggravation of AF vulnerability overtime