Delay differential equation-based models of cardiac tissue: Efficient implementation and effects on spiral-wave dynamics.

Delay differential equations (DDEs) recently have been used in models of cardiac electrophysiology, particularly in studies focusing on electrical alternans, instabilities, and chaos. A number of processes within cardiac cells involve delays, and DDEs can potentially represent mechanisms that result in complex dynamics both at the cellular level and at the tissue level, including cardiac arrhythmias. However, DDE-based formulations introduce new computational challenges due to the need for storing and retrieving past values of variables at each spatial location. Cardiac tissue simulations that use DDEs may require over 28 GB of memory if the history of variables is not managed carefully. This paper addresses both computational and dynamical issues. First, we present new methods for the numerical solution of DDEs in tissue to mitigate the memory requirements associated with the history of variables. The new methods exploit the different time scales of an action potential to dynamically optimize history size. We find that the proposed methods decrease memory usage by up to 95% in cardiac tissue simulations compared to straightforward history-management algorithms. Second, we use the optimized methods to analyze for the first time the dynamics of wave propagation in two-dimensional cardiac tissue for models that include DDEs. In particular, we study the effects of DDEs on spiral-wave dynamics, including wave breakup and chaos, using a canine myocyte model. We find that by introducing delays to the gating variables governing the calcium current, DDEs can induce spiral-wave breakup in 2D cardiac tissue domains.