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University of Glasgow

1. Noor Aziz, Muhamad Hifzhudin Bin. Analysis and applications of models of single-cell cardiac electrical excitation.

Degree: PhD, 2021, University of Glasgow

For over a century, cardiac electrophysiology modelling has been widely used for studying various problems of normal or abnormal heart rhythm, which is essential for understanding the disease mechanisms, provide accurate diagnoses and develop a new treatment. This thesis focuses on several analysis and applications of models in single-cell cardiac electrical excitation. In particular, I aim to study some typical challenges present in cardiac electrophysiology modelling, which is, variability in action potentials (AP) and their effects on cardiac anti-arrhythmic drugs, mechanisms of cardiac alternans and efficient numerical solver. To address the problems, I use various action potential models initially a range of biophysically detailed models, then focusing on a single simplified model. This thesis consists of two main parts, excluding the part for background and introductory materials. The first and most important part, in terms of effort and time spent, is devoted to the investigation of action potential variability in a population of rabbit ventricular myocytes and their effects on cardiac anti-arrhythmic drugs. To determine the distributions of ion channel conductance values that capture the electrophysiological heterogeneity measured in large populations of cells, I apply the experimentally-calibrated population of models introduced by Britton et al. (2013), constructing from randomly varied ion conductances combinations. The model population is further used to quantitatively predict the range of response to the application of hERG and L-type calcium channel blocks. I implement the methodologies on three different AP models to study the capability of the cell models in predicting the drug effects. The models are a rabbit AP model by Shannon et al. (2004) and two human AP models by Ten Tusscher et al. (2004) and O’Hara et al. (2011). The AP responses following channel blocks are compared and analysed. The second part of the thesis covers the analysis and application of a simplified ionic cardiac model. The model used is a modified version of caricature Noble model by Biktashev et al. (2008). Our first task is to propose the model as a generic model of cardiac electrophysiology by using a parameter estimation method. The model’s parameters are adjusted so that it can reproduce AP morphologies of various cell types. In particular, the model is fitted to three different AP models which are Purkinje model by Noble (1962), ventricular model by Luo and Rudy (1991) and atrial model by Courtemanche et al. (1998). The action potential duration restitution curve of targeted models are also reproduced. The similar model template now can be used for various regions of the heart by changing the parameter values. Furthermore, the modified caricature Noble model is fitted to experimental measurements of healthy and failing myocytes by McIntosh et al. (2000). I analyse the difference between parameter values from fitting works intending to find the physiological meaning for AP differences shown in experimental recordings.…

Subjects/Keywords: QA Mathematics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Noor Aziz, M. H. B. (2021). Analysis and applications of models of single-cell cardiac electrical excitation. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/81912/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.822071

Chicago Manual of Style (16th Edition):

Noor Aziz, Muhamad Hifzhudin Bin. “Analysis and applications of models of single-cell cardiac electrical excitation.” 2021. Doctoral Dissertation, University of Glasgow. Accessed March 01, 2021. http://theses.gla.ac.uk/81912/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.822071.

MLA Handbook (7th Edition):

Noor Aziz, Muhamad Hifzhudin Bin. “Analysis and applications of models of single-cell cardiac electrical excitation.” 2021. Web. 01 Mar 2021.

Vancouver:

Noor Aziz MHB. Analysis and applications of models of single-cell cardiac electrical excitation. [Internet] [Doctoral dissertation]. University of Glasgow; 2021. [cited 2021 Mar 01]. Available from: http://theses.gla.ac.uk/81912/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.822071.

Council of Science Editors:

Noor Aziz MHB. Analysis and applications of models of single-cell cardiac electrical excitation. [Doctoral Dissertation]. University of Glasgow; 2021. Available from: http://theses.gla.ac.uk/81912/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.822071

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