2 research outputs found
Stabilité de la réentrée anatomique dans le muscle cardiaque et annihilation par un protocole à deux stimulations : études de modélisation et aspects expérimentaux
Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal
Towards understanding the electrogram: theaoretical & experimental multiscale modelling of factors affecting action potential propagation in cardiac tissue
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.Open Acces