Clayton, R.H. orcid.org/0000-0002-8438-7518 (2018) Dispersion of Recovery and Vulnerability to Re-entry in a Model of Human Atrial Tissue With Simulated Diffuse and Focal Patterns of Fibrosis. Frontiers in Physiology, 9. 1052.
Abstract
Fibrosis in atrial tissue can act as a substrate for persistent atrial fibrillation, and can be focal or diffuse. Regions of fibrosis are associated with slowed or blocked conduction, and several approaches have been used to model these effects. In this study a computational model of 2D atrial tissue was used to investigate how the spatial scale of regions of simulated fibrosis influenced the dispersion of action potential duration (APD) and vulnerability to re-entry in simulated normal human atrial tissue, and human tissue that has undergone remodeling as a result of persistent atrial fibrillation. Electrical activity was simulated in a 10 × 10 cm square 2D domain, with a spatially varying diffusion coefficient as described below. Cellular electrophysiology was represented by the Courtemanche model for human atrial cells, with the model parameters set for normal and remodeled cells. The effect of fibrosis was modeled with a smoothly varying diffusion coefficient, obtained from sampling a Gaussian random field (GRF) with length scales of between 1.25 and 10.0 mm. Twenty samples were drawn from each field, and used to allocate a value of diffusion coefficient between 0.05 and 0.2 mm2 /ms. Dispersion of APD was assessed in each sample by pacing at a cycle length of 1,000 ms, followed by a premature beat with a coupling interval of 400 ms. Vulnerability to re-entry was assessed with an aggressive pacing protocol with pacing cycle lengths decreasing from 450 to 250 ms in 25 ms intervals for normal tissue and 300–150 ms for remodeled tissue. Simulated fibrosis at smaller spatial scales tended to lengthen APD, increase APD dispersion, and increase vulnerability to sustained re-entry relative to fibrosis at larger spatial scales. This study shows that when fibrosis is represented by smoothly varying tissue diffusion, the spatial scale of fibrosis has important effects on both dispersion of recovery and vulnerability to re-entry.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Clayton. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | atrial fibrillation; Courtemanche model; Gaussian random field; fibrosis; computer model; cardiac electrophysiology |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Computer Science (Sheffield) |
Funding Information: | Funder Grant number ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL (EPSRC) EP/K037145/1 ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL (EPSRC) EP/P010741/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Aug 2018 11:21 |
Last Modified: | 29 Aug 2018 11:21 |
Published Version: | https://doi.org/10.3389/fphys.2018.01052 |
Status: | Published |
Publisher: | Frontiers Media |
Refereed: | Yes |
Identification Number: | 10.3389/fphys.2018.01052 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:134991 |