Controlling spiral wave and spatiotemporal chaos in cardiac tissues by slowing sodium channel activation and inactivation

Abstract

Much evidence shows that the appearance and instability of the spiral wave in cardiac tissue can be linked to a kind of heart disease. Therefore there needs a method of controlling spiral wave more safely and effectively. The intelligent modification of specific ion channel to achieve desired control is the future direction of gene therapy in heart disease. The key question that has to be answered is which ion channel is the best candidate for controlling spiral wave. Modern biological technology has been able to make the mutation of sodium channel gene to change its relaxation time constant. In this paper, we adopt the Luo-Rudy phase I model to investigate how to regulate the relaxation time constant of sodium channel gate to control spiral wave and spatiotemporal chaos in cardiac tissues. We suggest a control strategy which slows down the rate of sodium current activation and inactivation by increasing the relaxation time constant of the sodium activation gate by up to times while its fast inactivation gate is clamped to 0.77. Numerical simulation results show that a gradual increase of will cause the activation gate of sodium current to reach maximum more slowly, and its amplitude is gradually reduced, so that the amplitude and duration of the action potential of cardiomyocyte are gradually reduced. When the factor is large enough, the spiral wave and spatiotemporal chaos cannot propagate in the medium except planar wave with low frequency. The reason is that the excitabilities of medium and wave speed significantly decrease. Therefore, the spiral waves and spatiotemporal chaos can be effectively eliminated when the control time is properly selected and the factor is large enough. Spiral wave and spatiotemporal chaos disappear mainly due to conduction obstacle. In some cases, spiral wave can disappear through the transition from spiral wave to target wave or tip retraction. Spatiotemporal chaos disappears after spatiotemporal chaos has evolved into meandering spiral wave. When the parameters are chosen properly, the phenomenon that spiral wave evolves into a self-sustained target wave is also observed. The corresponding target wave source is the pair of spiral waves with opposite rotation directions. These results can provide useful information for gene therapy in heart disease.