Quantifying the effects of ischaemia on electrophysiology and the ST segment of the ECG in human virtual ventricular cells and tissues

We have developed human virtual cell and tissue models of ischaemia, and used these models to quantify electrophysiological and ECG ST segment changes during subendocardial and global ischaemia. Our investigation has highlighted key differences with previous computational studies based on animal models: (i) propagation failure in the human model occurs with a smaller degree of hyperkalaemia compared to previously used animal models, due to differences in sodium channels kinetics; (ii) the human model is more sensitive to repolarising potassium currents during phase 3 repolarisation than the previously used animal models, and therefore the magnitude of the ATP-sensitive potassium current must be smaller in the human model to produce similar changes in action potential duration during ischaemia; and (iii) unlike in animal models where hyperkalaemia was identified as the major component of ST segment depression, we find in the human model that both anoxia and hyperkalaemia are responsible.