In silico optical modulation of spiral wave trajectories in cardiac tissue

Sayedeh Hussaini, Rupamanjari Majumder, Valentin Krinski, Stefan Luther
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Abstract

Life-threatening cardiac arrhythmias such as ventricular tachycardia and fibrillation are common precursors to sudden cardiac death. They are associated with the occurrence of abnormal electrical spiral waves in the heart that rotate at a high frequency. In severe cases, arrhythmias are combated with a clinical method called defibrillation, which involves administering a single global high-voltage shock to the heart to reset all its activity and restore sinus rhythm. Despite its high efficiency in controlling arrhythmias, defibrillation is associated with several negative side effects that render the method suboptimal. The best approach to optimize this therapeutic technique is to deepen our understanding of the dynamics of spiral waves. Here, we use computational cardiac optogenetics to study and control the dynamics of a single spiral wave in a two-dimensional, electrophysiologically detailed, light-sensitive model of a mouse ventricle. First, we illuminate the domain globally by applying a sequence of periodic optical pulses with different frequencies in the sub-threshold regime where no excitation wave is induced. In doing so, we obtain epicycloidal, hypocycloidal, and resonant drift trajectories of the spiral wave core. Then, to effectively control the wave dynamics, we use a method called resonant feedback pacing. In this approach, each global optical pulse is applied when the measuring electrode positioned on the domain registers a predefined value of the membrane voltage. This enables us to steer the spiral wave in a desired direction determined by the position of the electrode. Our study thus provides valuable mechanistic insights into the success or failure of global optical stimulation in executing efficient arrhythmia control.

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心脏组织螺旋波轨迹的硅学光学调制
危及生命的心律失常,如室性心动过速和纤颤是心脏性猝死的常见前兆。它们与心脏中以高频旋转的异常螺旋波的发生有关。在严重的情况下,心律失常是通过一种叫做除颤的临床方法来治疗的,这种方法包括对心脏进行一次全身高压电击,以重置其所有活动并恢复窦性心律。尽管它在控制心律失常方面效率很高,但除颤与一些负面副作用有关,使该方法不理想。优化这种治疗技术的最佳方法是加深我们对螺旋波动力学的理解。在这里,我们使用计算心脏光遗传学来研究和控制小鼠心室二维,电生理细节,光敏模型中的单个螺旋波的动力学。首先,我们在没有激发波的亚阈值区域内应用一系列不同频率的周期光脉冲来照亮整个区域。在此过程中,我们得到了螺旋波芯的表摆线、次摆线和共振漂移轨迹。然后,为了有效地控制波动动力学,我们使用了一种称为谐振反馈起搏的方法。在这种方法中,当定位在域上的测量电极注册到一个预定义的膜电压值时,施加每个全局光脉冲。这使我们能够将螺旋波转向由电极位置决定的所需方向。因此,我们的研究为有效控制心律失常的全局光学刺激的成功或失败提供了有价值的机制见解。
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