Real-time optical manipulation of cardiac conduction in intact hearts

Year: 2018

Authors: Scardigli M., Muellenbroich C., Margoni E., Cannazzaro S., Crocini C., Ferrantini C., Coppini R., Yan P., Loew L.M., Campione M., Bocchi L., Giulietti D., Cerbai E., Poggesi C., Bub G., Pavone F.S., Sacconi L.

Autors Affiliation: European Laboratory for Non-Linear Spectroscopy, Florence, 50019, Italy. National Institute of Optics, National Research Council, Florence, 50125, Italy. Department of Physics, University of Pisa, Pisa, 56127, Italy. Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, Florence, 50134, Italy. Division of Pharmacology, Department ‘NeuroFarBa’, University of Florence, Florence, 50139, Italy. R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine, Farmington, CT, 06030, USA. Neuroscience Institute, National Research Council, Padova, 35121, Italy. Department of Biomedical Sciences, Univercity ot Padua, Padua, 35121, Italy. Department of Information Engineering, University of Florence, Via S. Marta 3, Florence, 50139, Italy. Department of Physiology, McGill University, Montreal, Quebec, Canada. Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, 50019, Italy.

Abstract: Optogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all-optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide-field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free-run mode with submillisecond temporal resolution or in a closed-loop fashion: a tailored hardware and software platform allowed real-time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real-time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real-time resynchronization therapy and cardiac defibrillation. Furthermore, the closed-loop approach was applied to simulate a re-entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof-of-concept that a real-time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart.


Volume: 596 (17)      Pages from: 3841  to: 3858

More Information: This work was supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 654148 Laserlab-Europe, by National Institutes of Health (NIH Grant: R01 EB001963), by the Italian Ministry for Education, University and Research in the framework of the Flagship Project NANOMAX, by the Italian Ministry of Health (WFR GR-2011-02350583), by Telethon-Italy (GGP13162), by Ente Cassa di Risparmio di Firenze (private foundation), and by FAS-Salute ToRSADE project. C.C. holds a long-term fellowship from the Human Frontiers Science Program Organization.
KeyWords: Optogenetics, Optical mapping, Digital Micromirror Device, Cardiac electrophysiology
DOI: 10.1113/JP276283

Citations: 39
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