Pro-Arrhythmic Effects of Discontinuous Conduction at the Purkinje Fiber-Ventricle Junction Arising From Heart Failure-Induced Ionic Remodeling – Insights From Computational Modelling

Frontiers in Physiology

Chen Li¹  Kun Jian¹  Henggui Zhang²  Jules C. Hancox³ 

[1] Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, Manchester, United Kingdom;Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China;School of Physiology, Pharmacology and Neuroscience, Medical Sciences Building, University Walk, Bristol, United Kingdom;

关键词: heart failure;    ventricle;    Purkinje fiber;    electrical remodeling;    conduction block;    computational modelling;   

DOI  :  10.3389/fphys.2022.877428

来源: DOAJ

【 摘 要 】

Heart failure is associated with electrical remodeling of the electrical properties and kinetics of the ion channels and transporters that are responsible for cardiac action potentials. However, it is still unclear whether heart failure-induced ionic remodeling can affect the conduction of excitation waves at the Purkinje fiber-ventricle junction contributing to pro-arrhythmic effects of heart failure, as the complexity of the heart impedes a detailed experimental analysis. The aim of this study was to employ computational models to investigate the pro-arrhythmic effects of heart failure-induced ionic remodeling on the cardiac action potentials and excitation wave conduction at the Purkinje fiber-ventricle junction. Single cell models of canine Purkinje fiber and ventricular myocytes were developed for control and heart failure. These single cell models were then incorporated into one-dimensional strand and three-dimensional wedge models to investigate the effects of heart failure-induced remodeling on propagation of action potentials in Purkinje fiber and ventricular tissue and at the Purkinje fiber-ventricle junction. This revealed that heart failure-induced ionic remodeling of Purkinje fiber and ventricular tissue reduced conduction safety and increased tissue vulnerability to the genesis of the unidirectional conduction block. This was marked at the Purkinje fiber-ventricle junction, forming a potential substrate for the genesis of conduction failure that led to re-entry. This study provides new insights into proarrhythmic consequences of heart failure-induced ionic remodeling.

【 授权许可】

Unknown