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Title: Towards understanding the electrogram : theaoretical & experimental multiscale modelling of factors affecting action potential propagation in cardiac tissue
Author: Chang, Eugene Tze-Yeng
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Conduction of electrical excitation in cardiac tissue is mediated by multiple physiological factors. Abnormal conduction may lead to onset of arrhythmia, and is correlated experimentally and clinically with electrogram fractionation. In-silico modelling studies seek to characterise and predict the biophysical phenomena underlying electrical excitation and conduction, and thus inform experiment design, and diagnostic and treatment strategies. Existing models assume syncytial or continuum behaviour, which may not be an accurate assumption in the disease setting. The aim of this thesis is to correlate simple theoretical and experimental models of abnormal cardiac conduction, and investigate the limits of validity of the theoretical models under critical parameter choices. An experimental model of 1D continuum conduction is established in guinea pig pap- illary muscle to examine the relationship between mean tissue resistivity and electrical conduction velocity (CV). The relationship is compared with a monodomain tissue model coupled with the Luo Rudy I (LR1) guinea pig ventricular action potential, which obeys classical cable theory of conduction under pharmacological modulation. An experimental model of 1D discrete conduction is created via development of a micro-patterned culture model of the HL-1 atrial myocyte cell line on micro-electrode arrays, which has a lower baseline conduction velocity compared to conventional cardiomyocyte models. A novel 1D bidomain model of conduction of discrete cells coupled by gap junctions is proposed and validated, based on existing analytical and numerical studies, and coupled to the LR1 model. Simulation of slow conduction under modulation of physiological parameters reveal difference in the excitation conduction between continuum and discrete models. Electro- gram fractionation is observed in the discrete model, which may be a more realistic model of conduction in diseased myocardium. This work highlights possibilities and challenges in comparing and validating theoretical models with data from experiments, and the im- portance of choosing the appropriate modelling assumptions for the specific physiological question.
Supervisor: Siggers, Jennifer ; Sherwin, Spencer ; Peters, Nicholas Sponsor: British Heart Foundation ; Imperial College London
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral