The aim of this project is to link cellular events of electrical activation and contraction mechanics to the pumping function of the heart. Our sub-projects are being progressed at cell, tissue and whole organ scales with integration between the scales enabled by high performance computing.
At the cellular level, ion transport between sub-cellular compartments and across the cell membrane is modelled using systems of coupled ordinary differential equations. Excitation-contraction and mechano-electrical feedback are integrated at this micro-scale and embedded as a spatially distributed array of cells across anatomically-based models of heart muscle, over which the heart's electrical and mechanical properties are represented.
Schematic diagram of a complex cardiac electromechanics cellular model. The magnified portions illustrate components of the model for which multi-state models have been developed incorporating known biophysical detail.
Using this combined electromechanical framework, a number of important clinical and basic science questions are being addressed. These include where and how to pace a diseased heart, the effects of drug interaction on pump function, understanding mechanisms underpinning re-entrant arrhythmias and fibrillation, and how lack of blood flow affects excitation and contraction in the heart.
Investigating the coupling effects of tissue mechanics and activation has demonstrated possible mechanisms of cardiac arrhythmia, such as the formation of ectopic pacemakers due to mechano-sensitive ion channels, and break up of stable activation patterns into disorganised electrical activity akin to the degeneration of ventricular tachycardia into life-threatening fibrillation.
An anatomically based two-dimensional model of coupled excitation-contraction of the cardiac ventricles showing tissue deformation during electrical excitation. (Cell membrane voltage is scaled between -85 mV, blue, and +45 mV, red. The undeformed model is shown for reference.
The Cardiac Electromechanics Project gratefully acknowledges the support of its funding partners:
