Modeling calcium dynamics in human atria

Abstract

Mathematical models of cardiac electrophysiology are an important tool to investigate the underlying mecha- nisms responsible of arrhythmias. In particular, an im- portant question is the origin of atrial fibrillation (AF). Often, AF initiation is preceded by action potential dura- tion (APD) alternans, i.e., beat to beat oscillations in the APD, that arise at slower rates in patients with persistent AF than in those without AF or with paroxymal AF. Most of these arrhythmias appear as a consequence of malfunc- tions in calcium dynamics that produce oscillations in in- tracellular calcium, inducing subsequent APD alternans through electromechanical coupling. The aim of this work is to present a human atrial mathematical model that gives insight into the presence of calcium alternans. For that the model by Nygren et al was modified in order to reproduce calcium alternans at high pacing rhythms, as has been ob- served in experiments. The model reproduces the nonlin- ear dependence of gain and fractional SR Ca release upon SR Ca load. At fast pacing rates it presents alternans, due to slow recovery from inactivation of the RyR. Finally, we compare the results from this new model with other human atrial models well established in the literature.