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Heterogeneous Effects of Fibroblast-Myocyte Coupling in Different Regions of the Human Atria Under Conditions of Atrial Fibrillation

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Heterogeneous Effects of Fibroblast-Myocyte Coupling in Different Regions of the Human Atria Under Conditions of Atrial Fibrillation

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dc.contributor.author Sánchez-Arciniegas, Jorge Patricio es_ES
dc.contributor.author Gomez, Juan F es_ES
dc.contributor.author Martínez-Mateu, Laura es_ES
dc.contributor.author Romero Pérez, Lucia es_ES
dc.contributor.author Saiz Rodríguez, Francisco Javier es_ES
dc.contributor.author Trenor Gomis, Beatriz Ana es_ES
dc.date.accessioned 2020-05-19T03:02:40Z
dc.date.available 2020-05-19T03:02:40Z
dc.date.issued 2019-07-04 es_ES
dc.identifier.issn 1664-042X es_ES
dc.identifier.uri http://hdl.handle.net/10251/143622
dc.description.abstract [EN] Background: Atrial fibrillation (AF), the most common cardiac arrhythmia, is characterized by alteration of the action potential (AP) propagation. Under persistent AF, myocytes undergo electrophysiological and structural remodeling, which involves fibroblast proliferation and differentiation, modifying the substrate for AP propagation. The aim of this study was to analyze the effects on the AP of fibroblast-myocyte coupling during AF and its propagation in different regions of the atria. Methods: Isolated myocytes were coupled to different numbers of fibroblasts using the established AP models and tissue simulations were performed by randomly distributing fibroblasts. Fibroblast formulations were updated to match recent experimental data. Major ion current conductances of the myocyte model were modified to simulate AP heterogeneity in four different atrial regions (right atrium posterior wall, crista terminalis, left atrium posterior wall, and pulmonary vein) according to experimental and computational studies. Results: The results of the coupled myocyte-fibroblast simulations suggest that a more depolarized membrane potential and higher fibroblast membrane capacitance have a greater impact on AP duration and myocyte maximum depolarization velocity. The number of coupled fibroblasts and the stimulation frequency are determining factors in altering myocyte AP. Strand simulations show that conduction velocity tends to homogenize in all regions, while the left atrium is more likely to be affected by fibroblast and AP propagation block is more likely to occur. The pulmonary vein is the most affected region, even at low fibroblast densities. In 2D sheets with randomly placed fibroblasts, wavebreaks are observed in the low density (10%) central fibrotic zone and when fibroblast density increases (40%) propagation in the fibrotic region is practically blocked. At densities of 10 and 20% the width of the vulnerable window increases with respect to control but is decreased at 40%. Conclusion: Myocyte-fibroblast coupling characteristics heterogeneously affect AP propagation and features in the different atrial zones, and myocytes from the left atria are more sensitive to fibroblast coupling. es_ES
dc.description.sponsorship This work was supported by the "Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2013-2016" from the Ministerio de Economia, Industria y Competitividad of Spain and Fondo Europeo de Desarrollo Regional (FEDER) DPI2016-75799-R (AEI/FEDER, UE), and by the Direccion General de Politica Cientifica de la Generalitat Valenciana (PROMETEU 2016/088). es_ES
dc.language Inglés es_ES
dc.publisher Frontiers Media SA es_ES
dc.relation FEDER/DPI2016-75799-R es_ES
dc.relation GENERALITAT VALENCIANA/PROMETEO/2016/088 es_ES
dc.relation AEI/DPI2016-75799-R es_ES
dc.relation.ispartof Frontiers in Physiology es_ES
dc.relation.uri https://riunet.upv.es/handle/10251/120395
dc.rights Reconocimiento (by) es_ES
dc.subject Atrial fibrillation es_ES
dc.subject Computer simulation es_ES
dc.subject Structural remodeling es_ES
dc.subject Myofibroblast es_ES
dc.subject Vulnerability es_ES
dc.subject.classification TECNOLOGIA ELECTRONICA es_ES
dc.title Heterogeneous Effects of Fibroblast-Myocyte Coupling in Different Regions of the Human Atria Under Conditions of Atrial Fibrillation es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.3389/fphys.2019.00847 es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica es_ES
dc.description.bibliographicCitation Sánchez-Arciniegas, JP.; Gomez, JF.; Martínez-Mateu, L.; Romero Pérez, L.; Saiz Rodríguez, FJ.; Trenor Gomis, BA. (2019). Heterogeneous Effects of Fibroblast-Myocyte Coupling in Different Regions of the Human Atria Under Conditions of Atrial Fibrillation. Frontiers in Physiology. 10:1-13. https://doi.org/10.3389/fphys.2019.00847 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.3389/fphys.2019.00847 es_ES
dc.description.upvformatpinicio 1 es_ES
dc.description.upvformatpfin 13 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 10 es_ES
dc.identifier.pmid 31333496 es_ES
dc.identifier.pmcid PMC6620707 es_ES
dc.relation.pasarela S\405440 es_ES
dc.contributor.funder Generalitat Valenciana es_ES
dc.contributor.funder Agencia Estatal de Investigación es_ES
dc.contributor.funder European Regional Development Fund es_ES


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