Investigating the effect of oxygen deprivation of myocardium using computational modelling / Putri Nur Alia Nasuha Binti Mohd Nor

Faculty of Manufacturing and Mechatronic Engineering Technology

Thesis (Master of Science) -- Universiti Malaysia Pahang - 2026

Includes bibliographical references

The human heart relies on a complex and synchronized electrical conduction system to regulate its rhythmic contraction and maintain continuous blood circulation. Lifethreatening arrhythmias can be induced by disturbances in the conduction system, particularly those caused by myocardial infarction (MI). Myocardial infarction occurs when the coronary arteries are occluded, diminishing the oxygen and nutrition supply to the cardiac muscle. This condition promotes to tissue damage and initiates a series of rapid and complex changes in cardiac electrophysiology. One of the key challenges in cardiovascular research is understanding the early electrophysiological alterations that result from oxygen deprivation during ischaemia. Clinical studies often fail to capture these acute changes due to the delay in patient arrival at medical facilities, while animal models are limited by species differences and ethical concerns. Consequently, computational modelling has rapidly evolved into a prominent alternative to study cardiac behaviour under ischemic conditions in a controlled and repeatable environment. This work develops a unique mathematical model, termed the TTPO model, to examine the impact of oxygen deprivation on the electrophysiology of human ventricular myocytes. The TTPO model enhances the original electrophysiological model (TTP model), which replicates the dynamics of (Na⁺), (K⁺), and (Ca²⁺) across the cardiomyocyte membrane through experimentally confirmed equations. To reflect ischemia conditions, the model uses a modified oxygen diffusion module. This oxygen model is coupled to the electrophysiological system through energy-dependent pumps, including the sodiumpotassium ATPase, the calcium ATPase, and the sarcoplasmic reticulum calcium ATPase (SERCA). Although these pumps require ATP to function, the model simplifies the physiological pathway by directly linking oxygen concentration to pump efficiency without explicitly modelling ATP production. Creating a mathematical model that combines oxygen diffusion and cardiac electrophysiology, examining how oxygen deprivation affects ionic concentrations and membrane potential behavior, and verifying the model's predictions using data from earlier studies are the main objectives of this study. The TTPO model is simulated in both normal and ischemia situations and is constructed as a zero-dimensional system of ordinary differential equations. Results from the simulation demonstrate that reduced oxygen supply significantly alters intracellular ion concentrations and ion channel currents, especially affecting calcium dynamics and repolarization phases. Oxygen supply drops below β = 0.5, intracellular Na⁺ and Ca²⁺ accumulate, the resting membrane potential rises, and the action potential duration shortens. These changes contribute to the cardiac action potential's instability, establishing a scientific justification for the elevated incidence of arrhythmias throughout myocardial ischaemia. To sum up, the TTPO model provides a useful computational framework forexplore the metabolic-electrophysiological interplay in ischemic heart tissue. It addresses critical gaps in current experimental approaches and enhances our understanding of arrhythmia development due to oxygen deprivation This model can act as a basis for upcoming research projects that seek to design predictive tools or therapeutic interventions for ischemic heart disease and related cardiac disorders.