Journal article
Electrophysiological and anatomical factors determine arrhythmic risk in acute myocardial ischemia and its modulation by sodium current availability
- Abstract:
- Acute myocardial ischemia caused by coronary artery disease is one of the main causes of sudden cardiac death. Even though sodium current blockers are used as anti-arrhythmic drugs, decreased sodium current availability, also caused by mutations, has been shown to increase arrhythmic risk in ischemic patients. The mechanisms are still unclear. Our goal is to exploit perfect control and data transparency of over 300 high performance computing simulations to investigate arrhythmia mechanisms in acute myocardial ischemia with variable sodium current availability. The human anatomically-based torso-biventricular electrophysiological model used includes representation of realistic ventricular anatomy and fibre architecture, as well as ionic to electrocardiogram properties. Simulations show that reduced sodium current availability increased arrhythmic risk in acute regional ischemia due to both electrophysiological (increased dispersion of refractoriness across the ischemic border zone) and anatomical factors (conduction block from thin right ventricle to thick left ventricle). The asymmetric ventricular anatomy caused high arrhythmic risk specifically for ectopic stimuli originating from the right ventricle and ventricular base. Increased sodium current availability was ineffective in reducing arrhythmic risk for septo-basal ectopic excitation. Human-based multiscale modelling and simulations reveal key electrophysiological and anatomical factors determining arrhythmic risk in acute ischemia with variable sodium current availability.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.1MB, Terms of use)
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- Publisher copy:
- 10.1098/rsfs.2019.0124
Authors
- Publisher:
- Royal Society
- Journal:
- Interface Focus More from this journal
- Volume:
- 11
- Issue:
- 1
- Article number:
- 20190124
- Publication date:
- 2020-12-11
- Acceptance date:
- 2020-06-09
- DOI:
- EISSN:
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2042-8901
- ISSN:
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2042-8898
- Language:
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English
- Keywords:
- Pubs id:
-
1116142
- Local pid:
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pubs:1116142
- Deposit date:
-
2020-07-03
- ARK identifier:
Terms of use
- Copyright holder:
- Martinez-Navarro et al.
- Copyright date:
- 2020
- Rights statement:
- © 2020 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License, which permits unrestricted use, provided the original author and source are credited.
- Notes:
- This is the accepted manuscript version of the article. The final version will be available online from the Royal Society.
- Licence:
- CC Attribution (CC BY)
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