Spiral- and scroll-wave dynamics in mathematical models for canine and human ventricular tissue with varying Potassium and Calcium currents

We conduct a systematic,direct-numerical-simulation study,in mathematical models for ventricular tissue,of the dependence of spiral-and scroll-wave dynamics on GKr, the maximal conductance of the delayed rectifier Potassium current(IKr) channel,and the parameter γCao,which determines the magnitude and shape of the current ICaL for the L-type calcium-current channel,in both square and anatomically realistic,whole-ventricle simulation domains using canine and human models. We use ventricular geometry with fiber-orientation details and employ a physiologically realistic model for a canine ventricular myocyte. We restrict ourselves to an HRD-model parameter regime, which does not produce spiral- and scroll-wave instabilities because of other,well-studied causes like a very sharp action-potential-duration-restitution (APDR) curve or early after depolarizations(EADs) at the single-cell level. We find that spiral- or scroll-wave dynamics are affected predominantly by a simultaneous change in ICaL and IKr,rather than by a change in any one of these currents;other currents do not have such a large effect on these wave dynamics in this parameter regime of the HRD model.We obtain stability diagrams in the GKr -γCao plane.In the 3D domain,the geometry of the domain supports the confinement of the scroll waves and makes them more stable compared to their spiral-wave counterparts in 2D domain. We have also carried out a comparison of our HRD results with their counterparts for the human-ventricular TP06 model and have found important differences. In both these models,to make a transition,(from broken-wave to stable-scroll states or vice versa) we must simultaneously increase IKr and decrease ICaL;a modification of only one of these currents is not enough to effect this transition.