Date of Award

Spring 5-2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Electrical & Computer Engineering

Program/Concentration

Biomedical Engineering - Cardiovascular Engineering

Committee Director

Michel Audette

Committee Member

Makarand Deo

Committee Member

Anthony Owusu-Mensah

Committee Member

Anna Bulysheva

Abstract

Long QT Syndrome (LQTS) is an increasingly studied condition that leads to potentially fatal heart rhythm disorders, called arrhythmias, and sudden cardiac death. The alterations in the electrocardiograms (ECGs) seen in LQTS patients is caused by mutations to genes related to ion channels in cardiac cells. Computational modeling allows the mechanistic study of these ion channel mutations in LQTS by providing quantitative predictors of cardiac behavior in human and rabbit heart models. This work hypothesizes that the repolarization reserve in cardiac Purkinje cells (PC), that form the cardiac conduction system, is lower than that of ventricular myocytes (VM), resulting in a higher propensity of electrophysiological abnormalities in the form of spontaneous activity, particularly early and delayed afterdepolarizations (EADs and DADs, respectively). To investigate this hypothesis, detailed computational methods were created by incorporating experimental data. The computer models were then utilized to reproduce the experimentally observed behavior in single cells as well as 3-dimensional ventricular models. The computational results show more profound effects of the LQTS mutations on action potential duration (APD) prolongation in PCs when compared to VMs. Ectopic beats exist in isoproterenol conditions for human PCs. Future research includes determining the effect of these APD differences on the entirety of the heart using an anatomical 3D model of a rabbit heart.

DOI

10.25777/fbqm-9x48

ISBN

9798834003014

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