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Electrophysiological and anatomical factors determine arrhythmic risk in acute myocardial ischaemia and its modulation by sodium current availability.

Authors
  • Martinez-Navarro, Hector1
  • Zhou, Xin1
  • Bueno-Orovio, Alfonso1
  • Rodriguez, Blanca1
  • 1 Department of Computer Science, British Heart Foundation Centre of Research Excellence, University of Oxford, Parks Road, Oxford OX1 3QD, UK.
Type
Published Article
Journal
Interface focus
Publication Date
Feb 06, 2021
Volume
11
Issue
1
Pages
20190124–20190124
Identifiers
DOI: 10.1098/rsfs.2019.0124
PMID: 33335705
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Acute myocardial ischaemia 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 ischaemic 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 ischaemia 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 electrocardiographic properties. Simulations show that reduced sodium current availability increased arrhythmic risk in acute regional ischaemia due to both electrophysiological (increased dispersion of refractoriness across the ischaemic border zone) and anatomical factors (conduction block from the 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 ischaemia with variable sodium current availability. © 2020 The Authors.

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