Cellular, molecular and electrophysiological evaluation of atrial remodeling in rats with heart failure induced by radiofrequency ablation: impact on the mechanisms of atrial fibrillation

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice and the simultaneous involvement of AF and congestive heart failure (CHF) is associated with worsening of atrial structural remodeling, increasing the persistence of AF. Our group has developed a method of induction of CHF in rats by the technique of radiofrequency ablation. This model resulted in histopathological changes, ventricular dilatation and dysfunction similar to that played by the technique of coronary occlusion, generating a homogeneous model in size of lesions, with low mortality, and high reproducibility. We hypothesize that our model induces volume overload and atrial remodeling evenly and reproducible, validating it as a new model for the study of atrial remodeling and antifibrotic drug pirfenidone attenuates remodeling and inducibility of AF. Objectives: To assess the ineditism of atrial structural remodeling in rats with CHF induced by RF ablation. Methods: 85 Wistar rats (male, 280- 300g) are divided into groups SHAM (1, 4 and 12 weeks) Control (1, 4 and 12 weeks) and treated (1, 4 and 12 weeks). After RF ablation, shall be submitted to ECHO (1, 4 and 12 weeks, n = 85/85), invasive cardiac electrophysiology study (with bursts to induce atrial arrhythmias (1, 4 and 12 weeks, n = 75/85) and then sacrificed. Fragments of the atria will be evaluated by histology (Picrosirius staining for collagen quantification n = 75/85), cell culture groups and Control Treaty - 12 weeks (check if treatment with Pirfenidone reduces aggregation, differentiation to myofibroblasts and TGF- Beta1, n = 10/85), proteomics (Western Blotting TGF - ²1, type I and III Collagens and Connexin (Cx43 CXE - pSer368, n = 75/85) and 21 miRNA (expression involved in fibrosis fibrillation, n = 75/85). If we could validate the model of atrial remodeling, it may be useful in several lines of research aimed at attenuating atrial fibrosis, with undeniable clinical impact. (AU)