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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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Publisher copy:
10.1098/rsfs.2019.0124

Authors

More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Computer Science
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Computer Science
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Computer Science
Oxford college:
Keble College
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Computer Science
Role:
Author


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:
2042-8901
ISSN:
2042-8898


Language:
English
Keywords:
Pubs id:
1116142
Local pid:
pubs:1116142
Deposit date:
2020-07-03
ARK identifier:

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