Terminating spiral wave and spatiotemporal chaos in cardiac tissues by using late sodium current

Abstract

Most Na+ channels open transiently upon depolarization of cardiac cell membrane and then are quickly inactivated. However, some Na+ channels remain active, which generate the late sodium current during the action potential plateau. So far, late sodium current has been regarded as a relevant contributor to arrhythmias and its inhibition can suppress re-entrant and multifocal ventricular fibrillation so that its inhibition may become a novel therapeutic strategy to treat cardiac arrhythmias in the future. Therefore, how to inhibit late sodium current has received special attention. Since both the late sodium current and defibrillation shocks can lead to the increase of action potential duration, the late sodium current can be used to terminate ventricular fibrillation. However, the suppression of spiral wave and spatiotemporal chaos in cardiac tissues via late sodium current has been neglected. In this paper, we use the model of human heart to study the suppression of spiral wave and spatiotemporal chaos in two-dimensional cardiac tissue by generating late sodium current. We suggest that such a control strategy to induce late sodium current. The slow inactivation gate of sodium channel is clamped to 0.7 while the threshold voltage of corresponding fast inactivation gate is real-timely modulated. We first reduce the threshold voltage from 71.55 mV to 50.55 mV within the time interval T1, and then increase it from 50.55 mV to 71.55 mV within the time interval T2. When the threshold voltage returns to 71.55 mV, the changes of the relevant inactivation gates of sodium channel go back to normal dynamic state. Numerical simulation results show that when the control parameters are properly chosen, the control-induced late sodium current can effectively suppress spiral wave and spatiotemporal chaos even if there are some cardiac cells with spontaneous late sodium current. The advantage of the control scheme is that the control-induced late sodium current is small. The control duration is short because the spiral wave and spatiotemporal chaos disappear mainly due to the conduction obstacle. In a few cases, the spatiotemporal chaos disappears through the transition from spiral wave to target wave. We hope that these results may provide a new strategy to treat heart disease.