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Dispersion of cardiac action potential duration and the initiation of re-entry: A computational study

Clayton, R.H. and Holden, A.V. (2005) Dispersion of cardiac action potential duration and the initiation of re-entry: A computational study. Biomedical Engineering Online, 4 (11). ISSN 1475-925X


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BACKGROUND: The initiation of re-entrant cardiac arrhythmias is associated with increased dispersion of repolarisation, but the details are difficult to investigate either experimentally or clinically. We used a computational model of cardiac tissue to study systematically the association between action potential duration (APD) dispersion and susceptibility to re-entry.

METHODS: We simulated a 60 × 60 mm 2 D sheet of cardiac ventricular tissue using the Luo-Rudy phase 1 model, with maximal conductance of the K+ channel gKmax set to 0.004 mS mm-2. Within the central 40 × 40 mm region we introduced square regions with prolonged APD by reducing gKmax to between 0.001 and 0.003 mS mm-2. We varied (i) the spatial scale of these regions, (ii) the magnitude of gKmax in these regions, and (iii) cell-to-cell coupling.

RESULTS: Changing spatial scale from 5 to 20 mm increased APD dispersion from 49 to 102 ms, and the susceptible window from 31 to 86 ms. Decreasing gKmax in regions with prolonged APD from 0.003 to 0.001 mS mm-2 increased APD dispersion from 22 to 70 ms, and the susceptible window from <1 to 56 ms. Decreasing cell-to-cell coupling by changing the diffusion coefficient from 0.2 to 0.05 mm2 ms-1 increased APD dispersion from 57 to 88 ms, and increased the susceptible window from 41 to 74 ms.

CONCLUSION: We found a close association between increased APD dispersion and susceptibility to re-entrant arrhythmias, when APD dispersion is increased by larger spatial scale of heterogeneity, greater electrophysiological heterogeneity, and weaker cell-to-cell coupling.

Item Type: Article
Copyright, Publisher and Additional Information: © 2005 Clayton and Holden; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Institution: The University of Sheffield, The University of Leeds
Academic Units: The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Computer Science (Sheffield)
The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute of Membrane and Systems Biology (Leeds)
Depositing User: Sherpa Assistant
Date Deposited: 14 Mar 2006
Last Modified: 06 Jun 2014 15:52
Published Version: http://www.biomedical-engineering-online.com/conte...
Status: Published
Refereed: Yes
Identification Number: 10.1186/1475-925X-4-11
URI: http://eprints.whiterose.ac.uk/id/eprint/931

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