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Computational assessment of the functional role of sinoatrial node exit pathways in the human heart

AIM: The human right atrium and sinoatrial node (SAN) anatomy is complex. Optical mapping experiments suggest that the SAN is functionally insulated from atrial tissue except at discrete SAN-atrial electrical junctions called SAN exit pathways, SEPs. Additionally, histological imaging suggests the p...

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Autores principales: Kharche, Sanjay R., Vigmond, Edward, Efimov, Igor R., Dobrzynski, Halina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584965/
https://www.ncbi.nlm.nih.gov/pubmed/28873427
http://dx.doi.org/10.1371/journal.pone.0183727
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author Kharche, Sanjay R.
Vigmond, Edward
Efimov, Igor R.
Dobrzynski, Halina
author_facet Kharche, Sanjay R.
Vigmond, Edward
Efimov, Igor R.
Dobrzynski, Halina
author_sort Kharche, Sanjay R.
collection PubMed
description AIM: The human right atrium and sinoatrial node (SAN) anatomy is complex. Optical mapping experiments suggest that the SAN is functionally insulated from atrial tissue except at discrete SAN-atrial electrical junctions called SAN exit pathways, SEPs. Additionally, histological imaging suggests the presence of a secondary pacemaker close to the SAN. We hypothesise that a) an insulating border-SEP anatomical configuration is related to SAN arrhythmia; and b) a secondary pacemaker, the paranodal area, is an alternate pacemaker but accentuates tachycardia. A 3D electro-anatomical computational model was used to test these hypotheses. METHODS: A detailed 3D human SAN electro-anatomical mathematical model was developed based on our previous anatomical reconstruction. Electrical activity was simulated using tissue specific variants of the Fenton-Karma action potential equations. Simulation experiments were designed to deploy this complex electro-anatomical system to assess the roles of border-SEPs and paranodal area by mimicking experimentally observed SAN arrhythmia. Robust and accurate numerical algorithms were implemented for solving the mono domain reaction-diffusion equation implicitly, calculating 3D filament traces, and computing dominant frequency among other quantitative measurements. RESULTS: A centre to periphery gradient of increasing diffusion was sufficient to permit initiation of pacemaking at the centre of the 3D SAN. Re-entry within the SAN, micro re-entry, was possible by imposing significant SAN fibrosis in the presence of the insulating border. SEPs promoted the micro re-entry to generate more complex SAN-atrial tachycardia. Simulation of macro re-entry, i.e. re-entry around the SAN, was possible by inclusion of atrial fibrosis in the presence of the insulating border. The border shielded the SAN from atrial tachycardia. However, SAN micro-structure intercellular gap junctional coupling and the paranodal area contributed to prolonged atrial fibrillation. Finally, the micro-structure was found to be sufficient to explain shifts of leading pacemaker site location. CONCLUSIONS: The simulations establish a relationship between anatomy and SAN electrical function. Microstructure, in the form of intercellular gap junction coupling, was found to regulate SAN function and arrhythmia.
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spelling pubmed-55849652017-09-15 Computational assessment of the functional role of sinoatrial node exit pathways in the human heart Kharche, Sanjay R. Vigmond, Edward Efimov, Igor R. Dobrzynski, Halina PLoS One Research Article AIM: The human right atrium and sinoatrial node (SAN) anatomy is complex. Optical mapping experiments suggest that the SAN is functionally insulated from atrial tissue except at discrete SAN-atrial electrical junctions called SAN exit pathways, SEPs. Additionally, histological imaging suggests the presence of a secondary pacemaker close to the SAN. We hypothesise that a) an insulating border-SEP anatomical configuration is related to SAN arrhythmia; and b) a secondary pacemaker, the paranodal area, is an alternate pacemaker but accentuates tachycardia. A 3D electro-anatomical computational model was used to test these hypotheses. METHODS: A detailed 3D human SAN electro-anatomical mathematical model was developed based on our previous anatomical reconstruction. Electrical activity was simulated using tissue specific variants of the Fenton-Karma action potential equations. Simulation experiments were designed to deploy this complex electro-anatomical system to assess the roles of border-SEPs and paranodal area by mimicking experimentally observed SAN arrhythmia. Robust and accurate numerical algorithms were implemented for solving the mono domain reaction-diffusion equation implicitly, calculating 3D filament traces, and computing dominant frequency among other quantitative measurements. RESULTS: A centre to periphery gradient of increasing diffusion was sufficient to permit initiation of pacemaking at the centre of the 3D SAN. Re-entry within the SAN, micro re-entry, was possible by imposing significant SAN fibrosis in the presence of the insulating border. SEPs promoted the micro re-entry to generate more complex SAN-atrial tachycardia. Simulation of macro re-entry, i.e. re-entry around the SAN, was possible by inclusion of atrial fibrosis in the presence of the insulating border. The border shielded the SAN from atrial tachycardia. However, SAN micro-structure intercellular gap junctional coupling and the paranodal area contributed to prolonged atrial fibrillation. Finally, the micro-structure was found to be sufficient to explain shifts of leading pacemaker site location. CONCLUSIONS: The simulations establish a relationship between anatomy and SAN electrical function. Microstructure, in the form of intercellular gap junction coupling, was found to regulate SAN function and arrhythmia. Public Library of Science 2017-09-05 /pmc/articles/PMC5584965/ /pubmed/28873427 http://dx.doi.org/10.1371/journal.pone.0183727 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Kharche, Sanjay R.
Vigmond, Edward
Efimov, Igor R.
Dobrzynski, Halina
Computational assessment of the functional role of sinoatrial node exit pathways in the human heart
title Computational assessment of the functional role of sinoatrial node exit pathways in the human heart
title_full Computational assessment of the functional role of sinoatrial node exit pathways in the human heart
title_fullStr Computational assessment of the functional role of sinoatrial node exit pathways in the human heart
title_full_unstemmed Computational assessment of the functional role of sinoatrial node exit pathways in the human heart
title_short Computational assessment of the functional role of sinoatrial node exit pathways in the human heart
title_sort computational assessment of the functional role of sinoatrial node exit pathways in the human heart
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584965/
https://www.ncbi.nlm.nih.gov/pubmed/28873427
http://dx.doi.org/10.1371/journal.pone.0183727
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