A Heterogeneous Formulation of the Himeno et al Human Ventricular Myocyte Model for Simulation of Body Surface ECGs

Current multi-scale electrophysiology models capture the processes underlying ECG genesis under physiological and many disease conditions with high fidelity. However, proper representation of the extracellular milieu remains challenging. The human ventricular myocyte model by Himeno et al. is one of the first which faithfully represents the dependence of the action potential (AP) duration on the extracellular calcium concentration ([Ca ²⁺ ] _o ). Here, we present a heterogeneous formulation of the Himeno et al. cellular model and integrate it into a multi-scale framework to compute body surface ECGs. We propose 3 variants to account for transmural heterogeneity informed by experimental data and tuned to match AP level features such as repolarization stability. As shown before, an apico-basal gradient of I _Ks conductance is a likely mechanism causing concordant T-waves. Therefore, we increased I _Ks in the Himeno et al. model at the apex by a factor of 3.5 compared to the base to obtain an APD shortening of 12.5%. The setup comprising transmural and apico-basal heterogeneity yielded a physiological ventricular ECG. Our novel setup allows to study, for the first time, how realistic changes of the AP under hypo- and hypercalcaemic conditions translate to changes in the ECG. Resulting QT prolongation under hypocalcaemic conditions matched human experimental data.