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High-Resolution Endocardial and Epicardial Optical Mapping in a Sheep Model of Stretch-Induced Atrial Fibrillation
Published on: July 29, 2011
Self-terminating AF depends on electrical remodeling while persistent AF depends on additional structural changes in
Wim Anné1, Rik Willems, Patricia Holemans
1Department of Cardiology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium.
Journal of Molecular and Cellular Cardiology
|June 29, 2007
Summary
Electrical remodeling initiates atrial fibrillation (AF), but structural changes, including fibrosis driven by the angiotensin pathway and matrix metalloproteinases, are crucial for persistent AF. Inhibiting the angiotensin pathway reduces fibrosis and slows AF progression.
Area of Science:
- Cardiology
- Electrophysiology
- Translational Research
Background:
- Atrial fibrillation (AF) involves complex electrical and structural remodeling processes.
- Understanding the interplay between these remodeling types and specific molecular pathways is vital for developing effective treatments.
Purpose of the Study:
- To investigate the roles of electrical and structural remodeling in AF development using a rapid atrial pacing ovine model.
- To assess the contribution of the angiotensin pathway and matrix metalloproteinases (MMPs) to AF pathogenesis.
- To evaluate the impact of His bundle ablation (HBA) and angiotensin pathway inhibition on AF progression.
Main Methods:
- Thirty-five sheep underwent rapid atrial pacing, randomized to HBA or non-HBA groups.
- Ventricular pacing was initiated post-HBA.
- Sheep received either active treatment (quinapril+losartan) or placebo for 15 weeks.
- AF inducibility, persistence, ventricular rates, atrial MMP-2, TIMP-2 expression, and fibrosis were assessed.
Main Results:
- AF inducibility was similar across groups.
- Non-HBA sheep developed persistent AF significantly earlier than HBA sheep.
- Non-HBA sheep exhibited elevated ventricular rates, reduced atrial MMP-2, increased TIMP-2, and more fibrosis.
- Active treatment significantly reduced angiotensin II (AT-II), prevented atrial fibrogenesis, and slowed persistent AF development.
Conclusions:
- Electrical remodeling alone is sufficient for AF induction, whereas structural remodeling is necessary for AF persistence.
- Atrial fibrosis in this model results from increased AT-II expression coupled with altered MMP expression.
- Angiotensin pathway inhibition effectively suppresses atrial fibrosis and mitigates persistent AF development.
