Heterogeneity of Intrinsic Repolarization Properties Within the Human Heart: New Insights From Simulated Three-Dimensional Current Surfaces

Heterogeneity of repolarization properties is pivotal for both physiology and pathology of the heart and mathematical models of different cardiac cell types that are tuned to experimental data in order to reproduce it in silico. Repolarization heterogeneity is described most of the times with reference to one or the other of the many repolarization parameters, like action potential (AP) form and duration, or the maximum conductance of a given ion current, which are nonlinearly connected and frequently overdetermined. A compact representation of models dynamics would help their standardization, their use, and the understanding of the underlying physiology. A 3-D representation of cardiac AP derived from the measure of instantaneous current-voltage relationships during repolarization has been previously described. Here, it is shown that such a representation compactly summarizes important features of repolarization which are relevant particularly for what concerns its electrotonic modulation within the human heart. It is found that, according to the tested models, late phase of AP repolarization displays autoregenerativity only within the ventricle, and that this property is heterogeneously distributed across the wall. Three-dimensional current representations of the AP also provide precise estimation of the time course of membrane resistance, which changes throughout the heart, and can be used to predict entrainment of repolarization during AP propagation.