Recent human ventricular cell action potential models under varied ischaemic conditions

Investigating arrhythmic mechanisms during ischaemia is essential to improve clinical therapy. However, experimental data in human is scarce. Computational models are an essential tool for bridging this gap. Recent human ventricular cell action potential (AP) models have been built with data from healthy cells, thus their applicability to studies of ischaemia is mostly unknown. We have carried out a simulation study in single cell and tissue under normal and varied ischaemic conditions using 4 recent human models: ten Tusscher et al. 2006 (TP06), Grandi et al. 2010 (GPB), Carro et al. 2011 (CRLP), and O´hara et al. 2011 (ORd). We varied two parameters that play an important role in arrhythmogenesis during ischaemia: extracellular potassium concentration ([K⁺]_o) and peak conductance of the ATP-sensitive inward-rectifying potassium current (I_K(ATP)). To assess the applicability of these models to simulate ischaemia, we calculated AP duration (APD) and post-repolarisation refractoriness (PRR), biomarkers of arrhythmic risk. Results show that all models displayed the expected APD shortening due to IK(ATP) activation and hyperkalaemia. Furthermore, all models, apart from the ORd, reproduced an increase in PRR. The GPB did not show propagation of excitation for [K⁺]_o=9mM. This study suggests that the CRLP and TP06 models are the most suitable for performing human-specific simulations of arrhythmogenesis during myocardial ischaemia.