Dissolution of spiral wave's core using cardiac optogenetics

Rotating spiral waves in the heart are associated with life-threatening cardiac arrhythmias such as ventricular tachycardia and fibrillation. These arrhythmias are treated by a process called defibrillation, which forces electrical resynchronization of the heart tissue by delivering a single global high-voltage shock directly to the heart. This method leads to immediate termination of spiral waves. However, this may not be the only mechanism underlying successful defibrillation, as certain scenarios have also been reported, where the arrhythmia terminated slowly, over a finite period of time. Here, we investigate the slow termination dynamics of an arrhythmia in optogenetically modified murine cardiac tissue both in silico and ex vivo during global illumination at low light intensities. Optical imaging of an intact mouse heart during a ventricular arrhythmia shows slow termination of the arrhythmia, which is due to action potential prolongation observed during the last rotation of the wave. Our numerical studies show that when the core of a spiral is illuminated, it begins to expand, pushing the spiral arm towards the inexcitable boundary of the domain, leading to termination of the spiral wave. We believe that these fundamental findings lead to a better understanding of arrhythmia dynamics during slow termination, which in turn has implications for the improvement and development of new cardiac defibrillation techniques. Tachycardia and fibrillation are the most common precursors of sudden cardiac death. They are characterised by the significant increase in heart rate with or without irregular pumping, resulting in insufficient cardiac output. Research shows that high-frequency electrical spiral waves underlie these abnormal cardiac rhythms. These waves suppress the natural pacemaker of the heart to drive the overall cardiac electrical activity with poor efficiency. Thus, restoration of sinus rhythm requires the elimination of these waves using a technique called defibrillation. Here, a single high-voltage shock forces the heart's electrical activity to undergo an instantaneous phase reset (phase is a point of the system in an oscillatory cycle). Despite high success rate, electrical defibrillation has considerable negative side effects such as intense pain, trauma, and tissue damage. These disadvantages motivate the search for low-energy alternatives to conventional defibrillation. For this to work, a deeper understanding of arrhythmia dynamics during successful termination is required.Cardiac optogenetics opens a pathway for optical control of arrhythmia dynamics in a genetically modified tissue. Optogenetic experiments point to the existence of other slow mechanisms of successful defibrillation, which not fully understood. Exploring these mechanisms is crucial for the development of optimal defibrillation strategies to treat complex arrhythmias. Therefore, we have used a model based on cardiac optogenetics to study spiral wave termination using a single global light pulse at different light intensities and pulse lengths. We find that spiral wave termination at low light intensities occurs via a mechanism involving slow progressive dissolution of its core. Thus, we provide an explanation for the slow termination of arrhythmias at low defibrillation intensities. In addition, we have performed ex vivo studies in Langendorff-perfused mouse hearts controlling ventricular arrhythmias with a single global optical pulse. Optical imaging of an intact mouse heart during a ventricular arrhythmia shows slow termination of the arrhythmia, which is due to a known mechanism of action potential prolongation observed during the last rotation of the wave.