Session S63.3

Adaptive Modeling of Ionic Membrane Currents Improves Models of Cardiac Electromechanics

NHL Kuijpers*, HMM ten Eikelder, FW Prinzen

Eindhoven University of Technology
Eindhoven, Netherlands

Contraction of the heart is triggered by an electrical impulse propagating through the cardiac tissue. A change in heart rate or activation sequence by means of pacing induces changes in action potential (AP) morphology and duration. These changes are caused by electrical remodeling of ionic membrane currents and are reflected in the T wave in the electrocardiogram (ECG). Part of this remodeling process involves the calcium transient, which also leads to changes in mechanical behavior. Experimental observations indicate that electrical remodeling is triggered by changes in mechanical load (“mechano-electric feedback”). To simulate electrical remodeling, we introduce an adaptive modeling method in which stroke work per unit of tissue is used as a feedback signal to adapt the L-type Ca2+ current (I_CaL). We model the cardiac muscle as a string of segments that are electrically and mechanically coupled. In our model, contractile forces generated by the sarcomeres are related to the concentration of intracellular free Ca2+. Stroke work is determined for each segment by simulating the cardiac cycle. With this model, we investigated the effect of adaptation of I_CaL on electrophysiological and mechanical behavior. When I_CaL was homogeneously distributed, stroke work was small in early-activated segments and large in later-activated segments. With adaptation of I_CaL, contraction was more homogeneous, while the repolarization wave reversed. Our simulation results are in agreement with experimentally observed homogeneity in mechanics and heterogeneity in electrophysiology. In addition, the predicted changes in I_CaL correspond with changes that have been observed after three weeks of epicardial pacing. In conclusion, adaptive modeling of electrophysiology may lead to better predictions of cardiac electrophysiology and mechanics in coupled models of cardiac electromechanics.

(Abstract Control Number: 146)