Control of voltage-driven instabilities in cardiac myocytes with memory

Abstract

Sudden cardiac death is known to be associated with dynamical instabilities in the heart, and thus control of dynamical instabilities is considered a potential therapeutic strategy. Different control methods were developed previously, including time-delayed feedback pacing control and constant diastolic interval pacing control. Experimental, theoretical, and simulation studies have examined the efficacy of these control methods in stabilizing action potential dynamics. In this study, we apply these control methods to control complex action potential (AP) dynamics under two diseased conditions: early repolarization syndrome and long QT syndrome, in which voltage-driven instabilities occur in the presence of short-term cardiac memory. In addition, we also develop a feedback pacing method to stabilize these instabilities. We perform theoretical analyses using iterated map models and carry out numerical simulations of AP models. We show that under the normal condition where the memory effect is minimal, all three methods can effectively control the action potential duration (APD) dynamics. Under the two diseased conditions where the memory effect is exacerbated, constant diastolic pacing control is least effective, while the feedback pacing control is most effective. Under a very strong memory effect, all three methods fail to stabilize the voltage-driven instabilities. The failure of effective control is due to memory and the all-or-none AP dynamics which results in very steep changes in APD.