Accelerating Stabilization of Whole-heart Models after Changes in Cycle Length

Abstract

Parameter changes can cause long-term drift in membrane models. To reduce the cost of whole-heart simulations with such changes the stabilization can be performed in isolated-cell models, but it can then still take many beats to stabilize the full model. We hypothesized that differences in activation time leading to cycle length (CL) variability before the first beat contribute to this. To remove this variability we froze most state variables of the model until the sodium current activated. Simulations were performed with CL 400, 500, 600 and 1000 ms and modified Ten Tusscher-Panfilov 2006 dynamics. Isolated endocardial, mid-myocardial, and epicardial cells were simulated for 1000 beats. Their final states were then copied to a model of the whole human ventricles, which was run for 5 beats, with and without freezing. Stabilization of the full model took three to four beats. Freezing of the membrane state accelerated stabilization in some cell types but caused opposite drifts in others. Drifts were largest in the epicardial and mid-myocardial layers, and not in particular at their interfaces. Freezing of membrane state may help to accelerate stabilization but in our scenarios other types of drift dominate and may be aggravated by freezing, as it inhibits electrotonic interactions.