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Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study

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Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study

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dc.contributor.author Liberos Mascarell, Alejandro es_ES
dc.contributor.author Bueno-Orovio, Alfonso es_ES
dc.contributor.author Rodrigo Bort, Miguel es_ES
dc.contributor.author Ravens, Ursula es_ES
dc.contributor.author Hernández-Romero, Ismael es_ES
dc.contributor.author Fernández-Avilés, Francisco es_ES
dc.contributor.author Guillem Sánchez, María Salud es_ES
dc.contributor.author Rodríguez López, Blanca es_ES
dc.contributor.author Climent, Andreu M. es_ES
dc.date.accessioned 2017-07-14T07:26:11Z
dc.date.available 2017-07-14T07:26:11Z
dc.date.issued 2016-12
dc.identifier.issn 1547-5271
dc.identifier.uri http://hdl.handle.net/10251/85136
dc.description.abstract BACKGROUND Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments. OBJECTIVE The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies. METHODS A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations. RESULTS Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of I-Na and I-caL (P < .01), with no significant differences in the remaining currents. I-caL blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors because of an increase in rotor meandering (1.71 +/- 2.01cm(2)) and presented an increased efficacy in models with a depressed INa (P < .01). CONCLUSION Mathematical simulations based on a population of models representing intersubject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacologic strategies. Our results suggest that the underlying mechanism of the diverging success of I-caL block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities. es_ES
dc.description.sponsorship Supported by the Spanish Ministry of Education (FPU2010); the Wellcome Trust Fellowship 100246/Z/12/Z; Universitat Politecnica de Valencia; the Spanish Health Research Fund (PI13/00903); the Spanish Society of Cardiology; the Spanish Ministry of Science; Generalitat Valenciana Grants (ACIF/2013/021); and Innovation (Red RIC, PLE2009-0152). Drs. Rodriguez and Climent are equally contributing senior authors. en_EN
dc.language Inglés es_ES
dc.publisher Elsevier es_ES
dc.relation.ispartof Heart Rhythm es_ES
dc.rights Reconocimiento (by) es_ES
dc.subject Atrial fibrillation es_ES
dc.subject Ionic currents es_ES
dc.subject Rotor dynamics es_ES
dc.subject Calcium current es_ES
dc.subject Mathematical modeling es_ES
dc.subject.classification TECNOLOGIA ELECTRONICA es_ES
dc.title Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1016/j.hrthm.2016.08.028
dc.relation.projectID info:eu-repo/grantAgreement/WT//100246%2FZ%2F12%2FZ/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//PI13%2F00903/ES/Estudio preclínico de la implantación de parches de tejido cardiaco bioartificial electromecánicamente entrenados en un modelo de infarto de miocardio porcino. Desarrollo de bioreactores con estimulación electromecánica./ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GVA//ACIF%2F2013%2F021/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MICINN//PLE2009-0152/ES/INVESTIGACION TRASLACIONAL PARA EL DESARROLLO DE UN BANCO DE MATRICES DE ORGANOS Y DE ORGANOS Y TEJIDOS BIOARTIFICIALES AUTOLOGOS PARA TRASPLANTE/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Instituto Universitario de Telecomunicación y Aplicaciones Multimedia - Institut Universitari de Telecomunicacions i Aplicacions Multimèdia es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica es_ES
dc.description.bibliographicCitation Liberos Mascarell, A.; Bueno-Orovio, A.; Rodrigo Bort, M.; Ravens, U.; Hernández-Romero, I.; Fernández-Avilés, F.; Guillem Sánchez, MS.... (2016). Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study. Heart Rhythm. 13(12):2358-2365. https://doi.org/10.1016/j.hrthm.2016.08.028 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion http://doi.org/10.1016/j.hrthm.2016.08.028 es_ES
dc.description.upvformatpinicio 2358 es_ES
dc.description.upvformatpfin 2365 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 13 es_ES
dc.description.issue 12 es_ES
dc.relation.senia 324197 es_ES
dc.identifier.pmid 27569443 en_EN
dc.identifier.pmcid PMC5221730 en_EN
dc.contributor.funder Ministerio de Ciencia e Innovación es_ES
dc.contributor.funder Wellcome Trust es_ES
dc.contributor.funder Ministerio de Economía y Competitividad es_ES
dc.contributor.funder Generalitat Valenciana es_ES
dc.contributor.funder Ministerio de Educación es_ES
dc.contributor.funder Universitat Politècnica de València es_ES
dc.contributor.funder Sociedad Española de Cardiología es_ES


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