Optical Control of Cardiac Electrophysiology by the Photochromic Ligand AB2

Ventricular arrhythmias (VAs) may occur in both the structurally normal and diseased heart. Particularly, patients suffering from ischemic heart disease and heart failure are at high risk of recurrent VA eventually leading to sudden cardiac death (SCD). While high-voltage shocks delivered by an implantable defibrillator may prevent SCD, these interventions themselves impair quality of life and raise both morbidity and mortality, which accentuates the need for developing novel defibrillation techniques. Here, we report the photochromic ligand azobupivacaine 2 (AB2) to enable gradual control of cardiac electrophysiology by light. By reversibly blocking voltage-gated both Na ⁺ and K ⁺ channels, photoswitching of AB2 modulates both the ventricular effective refractory period and conduction velocity thereby converting VA into sinus rhythm in an ex-vivo intact heart model. Thus, AB2 opens the door to the development of an optical defibrillator based on photopharmacology.