Development of a Novel Multi-Dimensional Computational Model of the Teleost Fish Ventricle for the Study of Cardiac Thermal Tolerance

Abstract

Cardiac computational modelling has offered an alternative method to experimental cardiology for heart function studies. Although different electrophysiological models in several species have been developed, no such models exist for the fish heart. Fish are vertebrate ectothermic animals, and their body temperature is affected by temperature changes in their aquatic environment. Given the prominence of global warming effects, temperature changes and the rise of water temperature influence different organs in the fish body, including the heart. A better understanding of the process of thermal acclimation of the fish heart at single cell and tissue levels where cardiac ion channels and pumps remodel after prolonged exposure to a different temperature, is of scientific interest. Also, a 3D model based on an accurate anatomy model is a valuable tool for the study of ventricular electrical activities. Furthermore, investigating the effects of heart diseases on cardiac mechanical dynamics and the contracting dynamics of the human ventricular cells is also valuable to study. Thus, the objective of this thesis consists of three parts: In part I, a novel biophysically computer model for the teleost fish ventricular myocyte has been developed at the physiological body temperature of 4°C. First, novel formulations of the major ionic currents including , , and , were developed at 4°C and then incorporated into the basal model developed by Luo and Rudy for the guinea-pig ventricle myocytes. The developed model was then used to assess the effects of changing temperatures on ventricle electrical dynamics. The developed models matched experimental findings quantitatively. In Part II, a novel 3D biophysically and anatomically accurate model for the teleost ventricle was developed. First, a 3D geometry of the heart was reconstructed and segmented into the heart’s major chambers using a micro-CT scan with sustaining iodine technique. Then, the 3D geometry of the ventricle was incorporated into a 3D computational model to investigate the electrical excitation propagation in the teleost heart. In Part III, a multi-scale electromechanical model of human ventricle cells was modified to assess the impacts of hypertension (HP) on the contractile function of the human left ventricle myocytes. A single cell electromechanical model was modified by integrating experimental data from rat ventricular cells under Sham (control) and HP conditions. Simulations showed that HP prolonged and increased with no marked change in the sarcomere length or the contractile force at cellular level, but in 2D tissue simulations, there was an increase in the tissue’s vulnerability for initiation and maintenance of re-entrant excitation waves indicating a pro-arrhythmic effect of hypertension.

Date of Award	1 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jichen Li (Supervisor) & Henggui Zhang (Supervisor)