Interaction of activation-repolarization coupling and restitution properties in two models of human ventricular tissue

Dispersion of repolarization time (or recovery time) is known to be pro-arrhythmic, but not much is known about the rate-dependency of dispersion in repolarization time. The aim of this thesis was to investigate how heterogeneity in structure and function influence the dispersion of repolarization time following normal and premature beats in simulated human left ventricular tissue. The modelling tools were (1) geometrical models of tissue and fibre; (2) two cell models including a simple and a biophysically detailed human ventricular cell models; and (3) a monodomain model of ventricular tissue. During decreasing stimulus (S1S2) intervals, dispersion in repolarization time remained constant for normal beats while changed greatly for premature beats. In 2D tissue with structural discontinuities and no fibre orientation, the structural discontinuity was found to produce increased dispersion of repolarization, and slowing of propagation in the region between two structural discontinuities. In 3D tissue with functional heterogeneity (including a linear or a non-linear change in fibre orientation), the dispersion of repolarization time produced at different S1S2 intervals depended on the differences in local restitution. Thus longer S1S2 intervals could produce greater dispersion of repolarization time than shorter S1S2 intervals. Speed of depolarization conduction was also depended on the differences in local restitution. Therefore, combination of anisotropy and fibrosis could suppress the speed of depolarization conduction for premature beats in the mid-myocardial region of heterogeneous tissues composed of three ventricular cell types. The results suggest that 3D cubes of anisotropic fibrosis heterogeneous tissue may promote tissue vulnerably to ventricular arrhythmia. In an anatomically detailed left ventricular wedge with functional heterogeneity, long and short S1S2 intervals could produce greater dispersion of repolarization time than 3D cubes of tissues. These simulations have implications for our understanding of arrhythmias in the whole heart. Restitution profiles of repolarization time and profiles of dispersion in repolarization time (not action potential duration) may be used for estimating abnormal changes in repolarization time of premature beats and arrhythmia risk.