Whittaker, DG orcid.org/0000-0002-2757-5491, Benson, AP orcid.org/0000-0003-4679-9842, Teh, I et al. (2 more authors) (2019) Investigation of the Role of Myocyte Orientations in Cardiac Arrhythmia Using Image-Based Models. Biophysical Journal, 117 (12). pp. 2396-2408. ISSN 0006-3495
Abstract
Cardiac electrical excitation-propagation is influenced by myocyte orientations (cellular organization). Quantitatively understanding this relationship presents a significant research challenge, especially during arrhythmias in which excitation patterns become complex. Tissue-scale simulations of cardiac electrophysiology, incorporating both dynamic action potential behavior and image-based myocardial architecture, provide an approach to investigate three-dimensional (3D) propagation of excitation waves in the heart. In this study, we aimed to assess the importance of natural variation in myocyte orientations on cardiac arrhythmogenesis using 3D tissue electrophysiology simulations. Three anatomical models (i.e., describing myocyte orientations) of healthy rat ventricles—obtained using diffusion tensor imaging at 100 μm resolution—were registered to a single biventricular geometry (i.e., a single cardiac shape), in which the myocyte orientations could be represented by each of the diffusion tensor imaging data sets or by an idealized rule-based description. The Fenton-Karma cellular excitation model was modified to reproduce rat ventricular action potential duration restitution to create reaction-diffusion cardiac electrophysiology models. Over 250 3D simulations were performed to investigate the effects of myocyte orientations on the following: 1) ventricular activation, 2) location-dependent arrhythmia induction via rapid pacing, and 3) dynamics of re-entry averaged over multiple episodes. It was shown that 1) myocyte orientation differences manifested themselves in local activation times, but the influence on total activation time was small; 2) differences in myocyte orientations could critically affect the inducibility and persistence of arrhythmias for specific stimulus-location/cycle-length combinations; and 3) myocyte orientations alone could be an important determinant of scroll wave break, although no significant differences were observed in averaged arrhythmia dynamics between the four myocyte orientation scenarios considered. Our results show that myocyte orientations are an important determinant of arrhythmia inducibility, persistence, and scroll wave break. These findings suggest that where specificity is desired (for example, when predicting location-dependent, patient-specific arrhythmia inducibility), subject-specific myocyte orientations may be important.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Biophysical Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Biomedical Imaging Science Dept (Leeds) |
Funding Information: | Funder Grant number British Heart Foundation PG/16/74/32374 |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Oct 2019 14:38 |
Last Modified: | 25 Jun 2023 22:01 |
Status: | Published |
Publisher: | Biophysical Society |
Identification Number: | 10.1016/j.bpj.2019.09.041 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:151981 |