Wireless cardiac device for photopharmacological control of cardiac electrical activity

Introduction

Cardiac arrhythmias affect approximately 5% of the population and are associated with high morbidity and mortality. With the aging of the population, their prevalence is increasing, posing a major health challenge. Treatments for preventing or terminating arrhythmias exist (Antiarrhythmic drugs, Implantable cardioverter-defibrillators, ablation techniques…) but they come with important side effects (pro-arrhythmic effects, systemic toxicity…). Photopharmacology, with its high spatio-temporal resolution, emerged as a promising approach for modulating cardiac electrical activity.

Objective

We successfully demonstrated its ability to regulate ion channel activity ex vivo and in vivo using an external illumination source. The objective of this study, to consider further clinical application, is to demonstrate the ability of implantable cardiac device to activate photoactivatable peptides and interfere with cardiac activity.

Method

A wireless and battery free cardiac device has been previously developed and designed for rats allowing electrical and optical stimulations. We implanted the device on the right ventricular free wall. A photoactivatable analogue of AaHII, an arrhythmogenic peptide, has been intravenously injected and activated locally thanks to 380 nm illumination in anesthetized rats.

Results

We first successfully refined the surgical procedure and validated their tolerance over one month by analyzing electrical and mechanical parameters on ECG and echocardiography, circulating markers of heart injury and histology. The device is well tolerated over one month without any signs of inflammation or arrhythmias. We next demonstrated that 70% of the device-mediated photoactivations (5/7 rats), leads to a significant change in the electrical activity of the heart characterized by an increase of the T wave area on the ECG. Interestingly, all animals recovered quickly validating the local activation of the peptide.

Conclusion

This study is very promising for future applications of photopharmacology, and pave the road for local photoactivation of antiarrhythmic peptides to prevent or terminate arrhythmias in preclinical models.