Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.

Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as m...

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Main Authors: Juan F Gomez, Karen Cardona, Laura Martinez, Javier Saiz, Beatriz Trenor
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4108391?pdf=render
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author Juan F Gomez
Karen Cardona
Laura Martinez
Javier Saiz
Beatriz Trenor
author_facet Juan F Gomez
Karen Cardona
Laura Martinez
Javier Saiz
Beatriz Trenor
author_sort Juan F Gomez
collection DOAJ
description Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure.In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations.The electrical activity of human transmural ventricular tissue (5 cm × 5 cm) was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW) for reentry was evaluated following cross-field stimulation.No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components.Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity.
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spelling doaj.art-0a3697143a3b4919b0010be269ca478c2022-12-22T00:48:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10327310.1371/journal.pone.0103273Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.Juan F GomezKaren CardonaLaura MartinezJavier SaizBeatriz TrenorHeart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure.In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations.The electrical activity of human transmural ventricular tissue (5 cm × 5 cm) was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW) for reentry was evaluated following cross-field stimulation.No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components.Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity.http://europepmc.org/articles/PMC4108391?pdf=render
spellingShingle Juan F Gomez
Karen Cardona
Laura Martinez
Javier Saiz
Beatriz Trenor
Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.
PLoS ONE
title Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.
title_full Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.
title_fullStr Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.
title_full_unstemmed Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.
title_short Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.
title_sort electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis 2d simulation study
url http://europepmc.org/articles/PMC4108391?pdf=render
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AT lauramartinez electrophysiologicalandstructuralremodelinginheartfailuremodulatearrhythmogenesis2dsimulationstudy
AT javiersaiz electrophysiologicalandstructuralremodelinginheartfailuremodulatearrhythmogenesis2dsimulationstudy
AT beatriztrenor electrophysiologicalandstructuralremodelinginheartfailuremodulatearrhythmogenesis2dsimulationstudy