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Title: Biophysically detailed modelling of the pro-arrhythmic effects of heart failure-induced ionic remodelling
Author: Li, Chen
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2013
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Heart Failure is a common long term progressive and serious medical condition with high mortality and costly health services in the UK. By the year of 2010, there were around 90,000 people in the UK suffered from heart failure and in 2008, 10,000 heart failure patients were recorded death. Treatments of heart failure cost the National Health Service around £625 million every year. Although heart failure is highly pro-arrhythmic, the underlying mechanisms of the pro-arrhythmic effects of heart failure are not completely understood. Heart failure is associated with electrical remodelling of the properties and kinetics of some ionic channels responsible for the action potential of cardiac cells. However, it is still unclear whether this ionic channel remodelling can account for the pro-arrhythmic effects of heart failure as the complexity of the heart impedes a detailed experimental analysis. Biophysically detailed computational models have been developed in the last two decades, enabling the evaluation of experimental data. The aim of this thesis is to use arrhythmic mechanisms to investigate the pro-arrhythmic effects of heart failure-induced remodelling on the cardiac action potentials and Purkinje-ventricular junction. Single canine Purkinje fibre and ventricular cell models were developed to investigate the effects of heart failure-remodelled ionic channel currents on cell action potentials and identify optimal options for the potential clinical treatments. One-dimensional strand tissue model and three-dimensional wedge model were developed to further explore the effects of heart failure-induced remodelling in propagation of the canine Purkinje fibre, ventricle and Purkinje-ventricular junction. It was found that heart failure-induced remodelling on the Purkinje fibre and ventricle reduced the conduction safety and increased tissue’s vulnerability to the genesis of the unidirectional conduction block, especially at the Purkinje-ventricular junction, which may cause conduction failure, re-entry or both.
Supervisor: Zhang, Henggui Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Heart failure ; Purkinje fibre ; Ventricular cell ; Canine ; Purkinje-ventricular junction ; arrhythmic ; Conduction safety