Transmural heterogeneity in ion channel properties in the left ventricle optimizes pump function during natural electrical activation

In this simulation study, we hypothesize that transmural heterogeneity in ion channel properties serves to homogenize cardiac workload. Mechanics and electrophysiology were modeled both on cellular and tissue level. Endo-, midmyo- and epicardial cells differed in ion channel properties only. A preload-afterload experiment was simulated to analyze cardiac pump function during normal conduction from endo to epicardium (activation delay = 26 ms). For a homogeneous distribution, insufficient afterload (epi- or endocardial cells only) or increased diastolic stress (midmyocardial cells only) was observed. Simulating 50% midmyocardial cells, we observed the most homogenous distribution of workload, when midmyocardial cells were shifted towards the endocardium. We conclude that transmural heterogeneity in electrophysiology is essential for proper diastolic and systolic function and for a uniform distribution of workload across the ventricular wall.