RUOLO DELLA STIMOLAZIONE VAGALE SULLA PROLIFERAZIONE DEI FIBROBLASTI CARDIACI IN VIVO IN MODELLO ANIMALE DI FIBRILLAZIONE ATRIALE.

Introduction: Cardiac fibrosis is a pathological response that causes abnormalities in cardiac conduction and mechanical function, thereby contributing to the pathophysiology of a variety of cardiac conditions, including hypertrophy, failure, and arrhythmias. Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is a major cause of population morbidity and mortality. Recent studies have demonstrated that structural remodeling, involving prominent fibrotic changes, is a fundamental determinant of the perpetuation of AF, and contributes synergistically with electrical remodeling to the AF substrate. Atrial fibrosis is a hallmark feature of arrhythmogenic structural remodeling in clinical AF. Increased amounts of fibrous tissue occur not only in AF patients with identifiable cardiac diseases, but also in those with lone AF.There is a positive correlation between the amount of fibrosis and the persistence of AF,7 suggesting that AF may itself cause structural remodeling that in turn promotes AF. Evidence supporting this idea comes from animal studies showing that even when the ventricular rate is well-controlled, rapid atrial activation causes atrial fibrosis,9 and from work indicating that rapidly-activated atrial-derived cardiomyocytes secrete substances that enhance collagen synthesis by atrial fibroblasts. Methods We studied 60 male adult inbred Fisher rats. We divided the animals in 3 groups of 20 rats each. The first group received vagal stimulation and induce atrial fibrillation protocol (AF + VNS) and follow for 60 days, after 24 h 10 rats were treated with angiotensin II drugs for 60 days (AF + VNS + Ang II). The second group received vagal stimulation (VNS) and follow for 60 days, after after 24 h 10 rats were treated with angiotensin II drugs for 60 days (VNS + Ang II). The third group received induce atrial fibrillation protocol (AF) and follow for 60 days, after 24 h 10 rats were treated with angiotensin II drugs for 60 days (AF + Ang II). Results α1(I) and α1(III) procollagen mRNA levels increased statistically significant in the groups with atrial fibrillation associated or not with VNS in contrast with the group in sinus rhythm. The treatment with Angiotensin II receptor antagonist decrease proportionally in all groups the expression of mRNA levels for ventricular and atrial α1(I) and α1(III) procollagen. The VNS increase the expression of mRNA levels for ventricular and atrial α1(I) and α1(III) procollagen statistically significant between the two group in atrial fibrillation but not statistically significant when the group were treated with Angiotensin II receptor antagonist. The level of right ventricle was almost two time compare with both atria analysis or left ventricle analysis, the VNS increase the level of of mRNA levels for ventricular and atrial α1 (I) and α1(III) procollagen in the right ventricle also in the sinus rhythm group (p=0.5). Conclusion The study demonstrates that long-term VNS in the rats with permanent atria fibrillation induce an increase in cardiac procollagen mRNAs, cardiac fibrosis histologically evident with the presence of inflammatory cells and myocyte necrosis in both groups with atrial fibrillation with statistically significant of the increases in case of VNS; the highest increases of the cardiac procollagen mRNAs was observed in the right ventricle more that in the both atria, this increase was prevented from angiotensine II antagonist receptor therapy. We showed that VNS increased the inducibility of AF. We observed moreover the VNS associates with atrial fibrillation decrease significant the rate ventricular response.

Grantor dc:publisher

Università degli Studi di Milano

Year dc:date

2010

Author dc:creator

• C. DE ASMUNDIS

Contributors dc:contributor

• Tutor: Pedro Brugada ; coordinatore: Fabio Magrini
• MAGRINI, FABIO

• Atrial Fibrillation
• Atrial Fibrosis
• Animal model
• Settore MED/11 - Malattie dell'Apparato Cardiovascolare
• Settore MED/09 - Medicina Interna

Statement dc:rights

• info:eu-repo/semantics/closedAccess

Language dc:language

eng

Handle dc:identifier

http://hdl.handle.net/2434/150146

OAI identifier oai:identifier

oai:air.unimi.it:2434/150146