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

• Grant number: 13/23725-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2014
• Effective date (End): April 30, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Guilherme Drummond Fenelon Costa
• Grantee: Luís Felipe Neves dos Santos
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice and the simultaneous involvement of AF and congestive heart failure (CHF) was associated with a 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 uniqueness 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 able to validate the model of atrial remodeling, it may be used in several lines of research aimed at attenuating atrial fibrosis, with undeniable clinical impact.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DOS SANTOS, LUIS; ANTONIO, EDNEI L.; SERRA, ANDREY J.; YOSHIZAKI, AMANDA; SEIBT, LARISSA; SILVA, FLAVIO A.; COUTO, GISELE K.; ROSSONI, LUCIANA V.; TUCCI, PAULO; DE PAOLA, ANGELO A.; et al. Atrial fibrillation promotion in a rat model of heart failure induced by left ventricle radiofrequency ablation. IJC HEART & VASCULATURE, v. 21, p. 22-28, DEC 2018. (13/23725-0, 13/23553-5)