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The effects of fibrotic cell type and its density on atrial fibrillation dynamics: An in silico study

dc.contributor.authorPalacio L.C
dc.contributor.authorUgarte J.P
dc.contributor.authorSaiz J
dc.contributor.authorTobón C.
dc.date.accessioned2022-09-14T14:34:12Z
dc.date.available2022-09-14T14:34:12Z
dc.date.created2021
dc.identifier.issn20734409
dc.identifier.urihttp://hdl.handle.net/11407/7594
dc.descriptionRemodeling in atrial fibrillation (AF) underlines the electrical and structural changes in the atria, where fibrosis is a hallmark of arrhythmogenic structural alterations. Fibrosis is an important feature of the AF substrate and can lead to abnormal conduction and, consequently, mechanical dysfunction. The fibrotic process comprises the presence of fibrotic cells, including fibroblasts, myofibroblasts and fibrocytes, which play an important role during fibrillatory dynamics. This work assesses the effect of the diffuse fibrosis density and the intermingled presence of the three types of fibrotic cells on the dynamics of persistent AF. For this purpose, the three fibrotic cells were electrically coupled to cardiomyocytes in a 3D realistic model of human atria. Low (6.25%) and high (25%) fibrosis densities were implemented in the left atrium according to a diffuse fibrosis representation. We analyze the action potential duration, conduction velocity and fibrillatory conduction patterns. Additionally, frequency analysis was performed in 50 virtual electrograms. The tested fibrosis configurations generated a significant conduction velocity reduction, where the larger effect was observed at high fibrosis density (up to 82% reduction in the fibrocytes configuration). Increasing the fibrosis density intensifies the vulnerability to multiple re-entries, zigzag propagation, and chaotic activity in the fibrillatory conduction. The most complex propagation patterns were observed at high fibrosis densities and the fibrocytes are the cells with the largest proarrhythmic effect. Left-to-right dominant frequency gradients can be observed for all fibrosis configurations, where the fibrocytes configuration at high density generates the most significant gradients (up to 4.5 Hz). These results suggest the important role of different fibrotic cell types and their density in diffuse fibrosis on the chaotic propagation patterns during persistent AF. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.eng
dc.language.isoeng
dc.publisherMDPI
dc.relation.isversionofhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85117156503&doi=10.3390%2fcells10102769&partnerID=40&md5=f8222658e2b533d55fc189241cb0a1b5
dc.sourceCells
dc.titleThe effects of fibrotic cell type and its density on atrial fibrillation dynamics: An in silico study
dc.typeArticle
dc.rights.accessrightsinfo:eu-repo/semantics/restrictedAccess
dc.publisher.programCiencias Básicas
dc.type.spaArtículo
dc.identifier.doi10.3390/cells10102769
dc.subject.keyword3D modelseng
dc.subject.keywordAtrial fibrillationeng
dc.subject.keywordDiffuse fibrosiseng
dc.subject.keywordElectrograms leng
dc.relation.citationvolume10
dc.relation.citationissue10
dc.publisher.facultyFacultad de Ciencias Básicas
dc.affiliationPalacio, L.C., Materiales Nanoestructurados y Biomodelación (MATBIOM), Universidad de Medellín, Medellín, 050032, Colombia
dc.affiliationUgarte, J.P., Grupo de Investigación en Modelamiento y Simulación Computacional (GIMSC), Universidad de San Buenaventura, Medellín, 050010, Colombia
dc.affiliationSaiz, J., Centro de Investigación e Innovación en Bioingeniería (CI2B), Universitat Politècnica de València, Valencia, 46022, Spain
dc.affiliationTobón, C., Materiales Nanoestructurados y Biomodelación (MATBIOM), Universidad de Medellín, Medellín, 050032, Colombia
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dc.type.coarhttp://purl.org/coar/resource_type/c_6501
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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dc.identifier.reponamereponame:Repositorio Institucional Universidad de Medellín
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dc.identifier.instnameinstname:Universidad de Medellín


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