title: Mechanisms of perpetuation of atrial fibrillation in chronically dilated atria.
abstract: The progressive nature of atrial fibrillation (AF) has been demonstrated in numerous experimental as well as clinical investigations. Electrical remodeling (shortening of atrial refractoriness) develops within the first days of AF and contributes to the increase in stability of the arrhythmia. However, "domestication of AF" must also depend on other mechanisms since the stability of AF continues to increase after electrical remodeling has been completed. Chronic atrial stretch induces activation of numerous signaling pathways leading to cellular hypertrophy, fibroblast proliferation and tissue fibrosis. The resulting electro-anatomical substrate is characterized by increased non-uniform anisotropy and local conduction heterogeneities facilitating reentry in the dilated atria. Atrial fibrosis may lead to disruption of the electrical side-to-side junctions between muscle bundles. This can result in electrical dissociation between neighboring muscle bundles, i.e. they become activated out-of-phase. Recent mapping studies in goats with persistent AF showed that electrical dissociation can not only occur between neighboring muscle bundles but also in the third dimension, i.e. between the epicardial layer and the endocardial bundle network. Such endo-epicardial dissociation will significantly increase the number of wavefronts which can simultaneously be present in the atrial wall. This article reviews data suggesting a role of endo-epicardial dissociation in dilated and fibrillating atria, for the self-perpetuating nature of AF as well as its possible implications for therapeutic interventions.
authors: Department of Physiology, Cardiovascular Research Institute, University Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors: Jens
authors: J
authors: Eckstein
authors: Sander
authors: S
authors: Verheule
authors: Natasja M
authors: NM
authors: de Groot
authors: Natasja
authors: N
authors: de Groot
authors: Maurits
authors: M
authors: Allessie
authors: Ulrich
authors: U
authors: Schotten
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D016275:Atrial Function; D002908:Chronic Disease; D004108:Dilatation, Pathologic / Q000503:physiopathology; D004553:Electric Conductivity; D006325:Heart Atria / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology*; D008955:Models, Cardiovascular