Session S74.6

Transmural Heterogeneity in Ion Channel Properties in the Left Ventricle Optimizes Pump Function during Natural Electrical Activation

E Hermeling*, TM Verhagen, FW Prinzen, NHL Kuijpers

Maastricht University
Maastricht, Netherlands

Background: Experimental observations support transmural differences in electrophysiological properties across the left ventricle wall. The consequences of this heterogeneity for cardiac pump function, however, are poorly understood. In this modeling study, we hypothesize that transmural heterogeneity in ion channel properties serves to homogenize cardiac pump function in a heart with natural (endocardial to epicardial) impulse conduction.
Methods: To describe the mechanics of the model, 100 segments each consisting of a Hill’s three element model, were placed in series. A bidomain approach was used to describe electrical interaction between each segment, simulating the impulse conduction from endocardium towards epicardium (activation delay ~ 25 ms). Ion currents and excitation-contraction coupling were described by the Ten Tusscher and the Rice model IV, respectively. Epicardial, midmyocardial (M) and endocardial cells differed in ion-channel properties only. A preload-afterload experiment was simulated to analyze cardiac pump function in case of 1) complete homogeneity, using either only epicardial, M or endocardial cells 2) a gradual change in ion-channel properties from epi- to endocardium 3) 50% M cells located in the center of the wall or shifted towards epi- or endocardium.
Results: For a homogeneous distribution in electrophysiology, both epi- and endocardial cells were unable to generate sufficient afterload. Using M cells only, the relaxation phase was short, resulting in elevated diastolic stress. A gradual change in ion channel properties resulted in significantly lower external work performed by the ventricle (0.31 kJ/m3) than using 50% M cells (0.65 to 0.74 kJ/m3). Presence of the M cells predominantly in the subendocardial layers led to the most homogenous distribution of the external work over the ventricular wall.
Conclusions: Based on these simulations, we conclude that transmural heterogeneity in electrophysiological properties is essential for proper diastolic and systolic function and for a uniform distribution of workload across the ventricular wall.

(Abstract Control Number: 91)