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Effect of Na+-channel blockade on the three-dimensional substrate of atrial fibrillation in a model of endo-epicardial dissociation and transmural conduction

hal.structure.identifierDepartment of Physiology [Maastricht]
hal.structure.identifierCenter for Computational Medicine in Cardiology [Lugano]
dc.contributor.authorGHARAVIRI, Ali
hal.structure.identifierDepartment of Physiology [Maastricht]
dc.contributor.authorVERHEULE, Sander
hal.structure.identifierDepartment of Physiology [Maastricht]
hal.structure.identifierUniversity Hospital Basel [Basel]
dc.contributor.authorECKSTEIN, Jens
hal.structure.identifierInstitut de Mathématiques de Bordeaux [IMB]
hal.structure.identifierModélisation et calculs pour l'électrophysiologie cardiaque [CARMEN]
hal.structure.identifierIHU-LIRYC
dc.contributor.authorPOTSE, Mark
hal.structure.identifierCenter for Computational Medicine in Cardiology [Lugano]
dc.contributor.authorKRAUSE, Rolf
hal.structure.identifierCenter for Computational Medicine in Cardiology [Lugano]
hal.structure.identifierCardiocentro Ticino [Lugano]
dc.contributor.authorAURICCHIO, Angelo
hal.structure.identifierFontys Hogeschool Toegepaste Natuurwetenschappen = Fontys University of Applied Sciences [FONTYS]
hal.structure.identifierMaastricht University [Maastricht]
dc.contributor.authorKUIJPERS, Nico
hal.structure.identifierDepartment of Physiology [Maastricht]
dc.contributor.authorSCHOTTEN, Ulrich
dc.date.accessioned2024-04-04T03:04:00Z
dc.date.available2024-04-04T03:04:00Z
dc.date.issued2018-11-01
dc.identifier.issn1099-5129
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/193114
dc.description.abstractEnAims Atrial fibrillation (AF) is a progressive arrhythmia characterized by structural alterations that increase its stability. Both clinical and experimental studies showed a concomitant loss of antiarrhythmic drug efficacy in later stages of AF. The mechanisms underlying this loss of efficacy are not well understood. We hypothesized that structural remodelling may explain this reduced efficacy by making the substrate more three-dimensional. To investigate this, we simulated the effect of sodium (Na þ)-channel block on AF in a model of progressive transmural uncoupling. In a computer model consisting of two cross-connected atrial layers, with realistic atrial membrane behaviour, structural remodelling was simulated by reducing the number of connections between the layers. 100% of endo-epicardial connectivity represented a healthy atrium. At various degrees of structural remodelling, we assessed the effect of 60% sodium channel block on AF stability, endo-epicardial electrical activity dissociation (EED), and fibrilla-tory conduction pattern complexity quantified by number of waves, phase singularities (PSs), and transmural conduction ('breakthrough', BT). Sodium channel block terminated AF in non-remodelled but not in remodelled atria. The temporal excitable gap (EG) and AF cycle length increased at all degrees of remodelling when compared with control. Despite an increase of EED and EG, sodium channel block decreased the incidence of BT because of trans-mural conduction block. Sodium channel block decreased the number of waves and PSs in normal atrium but not in structurally remodelled atrium. This simple atrial model explains the loss of efficacy of sodium channel blockers in terminating AF in the presence of severe structural remodelling as has been observed experimentally and clinically. Atrial fibrillation termination in atria with moderate structural remodelling in the presence of sodium channel block is caused by reduction of AF complexity. With more severe structural remodelling, sodium channel block fails to promote synchronization of the two layers of the model.
dc.language.isoen
dc.publisherOxford University Press (OUP)
dc.subject.enAtrial fibrillation
dc.subject.enTransmural conduction
dc.subject.enComputer model
dc.subject.enThree-dimensional
dc.subject.enSodium-channel block
dc.subject.enElectrical dissociation
dc.title.enEffect of Na+-channel blockade on the three-dimensional substrate of atrial fibrillation in a model of endo-epicardial dissociation and transmural conduction
dc.typeArticle de revue
dc.identifier.doi10.1093/europace/euy236
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologie/Cardiologie et système cardiovasculaire
dc.description.sponsorshipEuropeEU Training Network on Novel Targets and Methods in Atrial Fibrillation
bordeaux.journalEP-Europace
bordeaux.pageiii69 - iii76
bordeaux.volume20
bordeaux.hal.laboratoriesInstitut de Mathématiques de Bordeaux (IMB) - UMR 5251*
bordeaux.issuesuppl 3
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-01933818
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-01933818v1
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