OPTOCARD · Panoramic optical manipulation of cardiac electrical dynamics: a novel tool to study complex arrhythmias

Cardiovascular diseases are the most common cause of death worldwide, and a substantial number of these deaths are caused by cardiac arrhythmias. Heterogeneities in repolarisation time (RT), which are caused by prolongation or abbreviation of action potential duration (APD) in certain areas of the heart can underly arrhythmias. Inherited disease, as well as acquired heart disease such as myocardial infarction can induce RT heterogeneities (RTH). While recent studies shed some light on how RTH drive arrhythmias, current experimental techniques lack flexibility of affected area size, and the conditions facilitating arrhythmias therefore remain elusive. Recently, a novel method to generate RTH was described, applying low-intensity optical stimulation in murine hearts expressing the light-activated ion channel channelrhodopsin-2 (ChR2), depolarising resting membrane potential (RMP) and prolonging APD in a spatially specific manner. While this intriguing approach would allow to study the impact of RTH on arrhythmogenesis in a highly flexible manner, current experimental platforms lack the abilities to perform this assessment. Therefore, we propose to construct a novel panoramic optical platform, consisting of 4 cameras and 4 digital projectors, to allow for optical stimulation as well as recording across the entire ventricular surface. In addition, we explore pharmacological approaches to enhance the RT gradient between the optically stimulated and non-stimulated area, identifying drugs prolonging APD in an RMP-modulated manner. The capability of manipulating RT across the whole heart surface with unprecedented spatio-temporal resolution will be employed to understand the mechanisms underlying arrhythmia induction and rotor maintenance. The development of this ground-breaking methodology will provide fundamental insights in cardiac disease, boosting new therapeutic strategies and will represent a whole new approach for the investigation of cardiac physiology in general.