Shining light on cardiac electrophysiology: From detection to intervention, from basic research to translational applications.

Cardiac arrhythmias are an important group of cardiovascular diseases, which can occur alone or in association with other cardiovascular diseases. The development of cardiac arrhythmias cannot be separated from changes in cardiac electrophysiology, and the investigation and clarification of cardiac electrophysiological changes are beneficial for the treatment of cardiac arrhythmias. However, electrical energy-based pacemakers and defibrillators, which are widely used to treat arrhythmias, still have certain disadvantages. Thereby, optics promises to be used for optical manipulation and its use in biomedicine is increasing. Since visible light is readily absorbed and scattered in living tissues and tissue penetration is shallow, optical modulation for cells and tissues requires conversion media that convert light energy into bioelectrical activity. In this regard, fluorescent dyes, light-sensitive ion channels, and optical nanomaterials can assume this role, the corresponding optical mapping technology, optogenetics technology, and optical systems based on luminescent nanomaterials have been introduced into the research in cardiovascular field and are expected to be new tools for the study and treatment of cardiac arrhythmias. In addition, infrared and near-infrared light has strong tissue penetration, which is one of the excellent options of external trigger for achieving optical modulation, and is also widely used in the study of optical modulation of biological activities. Here, the advantages of optical applications are summarized, the research progresses and emerging applications of optical-based technologies as detection and intervention tools for cardiac electrophysiological are highlighted. Moreover, the prospects for future applications of optics in clinical diagnosis and treatment are discussed.

Optical capture and defibrillation in rats with monocrotaline-induced myocardial fibrosis 1 year after a single intravenous injection of adeno-associated virus channelrhodopsin-2.

BACKGROUND: Optogenetics uses light to regulate cardiac rhythms and terminate malignant arrhythmias. OBJECTIVE: The purpose of this study was to investigate the long-term validity of optical capture properties based on virus-transfected channelrhodopsin-2 (ChR2) and evaluate the effects of optogenetic-based defibrillation in an in vivo rat model of myocardial fibrosis enhanced by monocrotaline (MCT). METHODS: Fifteen infant rats received jugular vein injection of adeno-associated virus (AAV). After 8 weeks, 5 rats were randomly selected to verify the effectiveness ChR2 transfection. The remaining rats were administered MCT at 11 months. Four weeks after MCT, the availability of 473-nm blue light to capture heart rhythm in these rats was verified again. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were induced by burst stimulation on the basis of enhanced myocardial fibrosis, and the termination effects of the optical manipulation were tested. RESULTS: Eight weeks after AAV injection, there was ChR2 expression throughout the ventricular myocardium as reflected by both fluorescence imaging and optical pacing. Four weeks after MCT, significant myocardial fibrosis was achieved. Light could still trigger the corresponding ectopic heart rhythm, and the pulse width and illumination area could affect the light capture rate. VT/VF was induced successfully in 1-year-observation rats, and the rate of termination of VT/VF under light was much higher than that of spontaneous termination. CONCLUSION: Viral ChR2 transfection can play a long-term role in the rat heart, and light can successfully regulate heart rhythm and defibrillate after cardiac fibrosis.