Towards understanding the electrogram: theaoretical & experimental multiscale modelling of factors affecting action potential propagation in cardiac tissue
Author(s)
Chang, Eugene Tze-Yeng
Type
Thesis
Abstract
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.
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.
Version
Open Access
Date Issued
2013-07
Date Awarded
2013-07
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Siggers, Jennifer
Sherwin, Spencer
Peters, Nicholas
Sponsor
British Heart Foundation ; Imperial College London
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)