Modelling Cardiac Mechano-Energetics

Abstract

This thesis focuses on the computationally efficient, mechanistically detailed modelling of cardiac cross-bridge cycling and the benefit of incorporating such a model into tissue-level cardiac models. A zero –dimensional (0D) model of excitation-contraction was constructed via coupling of the Rice-Tran cross-bridge, Hinch Ca2+, and Rogers action potential models, resulting in the generation of the combined Hinch-Rogers-Tran model (HRT). The capabilities of the combined model were tested, with the HRT model successfully replicating isometric and quick-release experimental data. Success in reproducing experimental observations demonstrates the validity of the HRT model. Knowing that the HRT model can replicate physiological trends, it is then used to study more complex cross-bridge cycling dynamics. The combined model produced force-length work-loops, subtle trends in end-systolic behaviour, and force-calcium loops. By using the HRT model, events and mechanistic details beyond the scope of current experimental technologies were explored. With the HRT model capable of performing 0D work-loops, it is intended that future research projects will use the model within tissue-level or ventricular-level models. Using the HRT as a subcomponent would allow researchers to generate tissue or organ models that have independently functioning cells, a novel concept that allows for the exploration of tissue heterogeneity.