Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis

Background and Objectives: Enhanced beat-to-beat variability of ventricular repolarization (BVR) has been linked to arrhythmias and sudden cardiac death. Recent experimental studies on human left ventricular epicardial electrograms have shown that BVR closely interacts with low-frequency (LF) oscill...

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Autores: Sampedro-Puente, David Adolfo, Fernandez-Bes, Jesús, Porter, Bradley, Duijvenboden, Stef an van, Taggart, Peter, Pueyo, Esther
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Zaragoza
Repositorio:Zaguán. Repositorio Digital de la Universidad de Zaragoza
OAI Identifier:oai:zaguan.unizar.es:96049
Acceso en línea:http://zaguan.unizar.es/record/96049
Access Level:acceso abierto
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spelling Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for ArrhythmogenesisSampedro-Puente, David AdolfoFernandez-Bes, JesúsPorter, BradleyDuijvenboden, Stef an vanTaggart, PeterPueyo, EstherBackground and Objectives: Enhanced beat-to-beat variability of ventricular repolarization (BVR) has been linked to arrhythmias and sudden cardiac death. Recent experimental studies on human left ventricular epicardial electrograms have shown that BVR closely interacts with low-frequency (LF) oscillations of activation recovery interval during sympathetic provocation. In this work human ventricular computational cell models are developed to reproduce the experimentally observed interactions between BVR and its LF oscillations, to assess underlying mechanisms and to establish a relationship with arrhythmic risk. Materials and Methods: A set of human ventricular action potential (AP) models covering a range of experimental electrophysiological characteristics was constructed. These models incorporated stochasticity in major ionic currents as well as descriptions of ß-adrenergic stimulation and mechanical effects to investigate the AP response to enhanced sympathetic activity. Statistical methods based on Automatic Relevance Determination and Canonical Correlation Analysis were developed to unravel individual and common factors contributing to BVR and LF patterning of APD in response to sympathetic provocation. Results: Simulated results reproduced experimental evidences on the interactions between BVR and LF oscillations of AP duration (APD), with replication of the high inter-individual variability observed in both phenomena. ICaL, IKr and IK1 currents were identified as common ionic modulators of the inter-individual differences in BVR and LF oscillatory behavior and were shown to be crucial in determining susceptibility to arrhythmogenic events. Conclusions: The calibrated family of human ventricular cell models proposed in this study allows reproducing experimentally reported interactions between BVR and LF oscillations of APD. Ionic factors involving ICaL, IKr and IK1 currents are found to underlie correlated increments in both phenomena in response to sympathetic provocation. A link to arrhythmogenesis is established for concomitantly elevated levels of BVR and its LF oscillations.2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://zaguan.unizar.es/record/96049reponame:Zaguán. Repositorio Digital de la Universidad de Zaragozainstname:Universidad de ZaragozaInglésinfo:eu-repo/grantAgreement/ES/DGA-FEDER/T39-17R-BSICoSinfo:eu-repo/grantAgreement/ES/DGA-FSE/LMP124-18info:eu-repo/grantAgreement/EUR/ERC-2014-StG-638284/info:eu-repo/grantAgreement/ES/MINECO/DPI2016-75458-Rinfo:eu-repo/semantics/openAccessoai:zaguan.unizar.es:960492026-05-29T13:59:51Z
dc.title.none.fl_str_mv Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis
title Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis
spellingShingle Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis
Sampedro-Puente, David Adolfo
title_short Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis
title_full Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis
title_fullStr Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis
title_full_unstemmed Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis
title_sort Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis
dc.creator.none.fl_str_mv Sampedro-Puente, David Adolfo
Fernandez-Bes, Jesús
Porter, Bradley
Duijvenboden, Stef an van
Taggart, Peter
Pueyo, Esther
author Sampedro-Puente, David Adolfo
author_facet Sampedro-Puente, David Adolfo
Fernandez-Bes, Jesús
Porter, Bradley
Duijvenboden, Stef an van
Taggart, Peter
Pueyo, Esther
author_role author
author2 Fernandez-Bes, Jesús
Porter, Bradley
Duijvenboden, Stef an van
Taggart, Peter
Pueyo, Esther
author2_role author
author
author
author
author
description Background and Objectives: Enhanced beat-to-beat variability of ventricular repolarization (BVR) has been linked to arrhythmias and sudden cardiac death. Recent experimental studies on human left ventricular epicardial electrograms have shown that BVR closely interacts with low-frequency (LF) oscillations of activation recovery interval during sympathetic provocation. In this work human ventricular computational cell models are developed to reproduce the experimentally observed interactions between BVR and its LF oscillations, to assess underlying mechanisms and to establish a relationship with arrhythmic risk. Materials and Methods: A set of human ventricular action potential (AP) models covering a range of experimental electrophysiological characteristics was constructed. These models incorporated stochasticity in major ionic currents as well as descriptions of ß-adrenergic stimulation and mechanical effects to investigate the AP response to enhanced sympathetic activity. Statistical methods based on Automatic Relevance Determination and Canonical Correlation Analysis were developed to unravel individual and common factors contributing to BVR and LF patterning of APD in response to sympathetic provocation. Results: Simulated results reproduced experimental evidences on the interactions between BVR and LF oscillations of AP duration (APD), with replication of the high inter-individual variability observed in both phenomena. ICaL, IKr and IK1 currents were identified as common ionic modulators of the inter-individual differences in BVR and LF oscillatory behavior and were shown to be crucial in determining susceptibility to arrhythmogenic events. Conclusions: The calibrated family of human ventricular cell models proposed in this study allows reproducing experimentally reported interactions between BVR and LF oscillations of APD. Ionic factors involving ICaL, IKr and IK1 currents are found to underlie correlated increments in both phenomena in response to sympathetic provocation. A link to arrhythmogenesis is established for concomitantly elevated levels of BVR and its LF oscillations.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://zaguan.unizar.es/record/96049
url http://zaguan.unizar.es/record/96049
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/ES/DGA-FEDER/T39-17R-BSICoS
info:eu-repo/grantAgreement/ES/DGA-FSE/LMP124-18
info:eu-repo/grantAgreement/EUR/ERC-2014-StG-638284/
info:eu-repo/grantAgreement/ES/MINECO/DPI2016-75458-R
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv
publisher.none.fl_str_mv
dc.source.none.fl_str_mv reponame:Zaguán. Repositorio Digital de la Universidad de Zaragoza
instname:Universidad de Zaragoza
instname_str Universidad de Zaragoza
reponame_str Zaguán. Repositorio Digital de la Universidad de Zaragoza
collection Zaguán. Repositorio Digital de la Universidad de Zaragoza
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