Optogenetics design of mechanistically-based stimulation patterns for cardiac defibrillation

Year: 2016

Authors: Crocini C., Ferrantini C., Coppini R., Scardigli M., Yan P., Loew L.M., Smith G., Cerbai E., Poggesi C., Pavone F.S., Sacconi L.

Autors Affiliation: European Laboratory for Non-Linear Spectroscopy, 50019 Sesto Fiorentino, Italy; National Institute of Optics, National Research Council, 50125 Florence, Italy; Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy; Division of Pharmacology, Department “NeuroFarBa,” University of Florence, 50139 Florence, Italy; R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030, USA; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK; Department of Physics and Astronomy, University of Florence, 50019 Sesto Fiorentino, Italy.

Abstract: Current rescue therapies for life-threatening arrhythmias ignore the pathological electro-anatomical substrate and base their efficacy on a generalized electrical discharge. Here, we developed an all-optical platform to examine less invasive defibrillation strategies. An ultrafast wide-field macroscope was developed to optically map action potential propagation with a red-shifted voltage sensitive dye in whole mouse hearts. The macroscope was implemented with a random-access scanning head capable of drawing arbitrarily-chosen stimulation patterns with sub-millisecond temporal resolution allowing precise epicardial activation of Channelrhodopsin2 (ChR2). We employed this optical system in the setting of ventricular tachycardia to optimize mechanistic, multi-barrier cardioversion/defibrillation patterns. Multiple regions of conduction block were created with a very high cardioversion efficiency but with lower energy requirements as compared to whole ventricle interventions to interrupt arrhythmias. This work demonstrates that defibrillation energies can be substantially reduced by applying discrete stimulation patterns and promotes the progress of current anti-arrhythmic strategies.


Volume: 6      Pages from: 35628-1  to: 35628-7

More Information: We thank Marie-Caroline Mullenbroich for useful suggestions during the manuscript preparation. This project has received funding from the European Union Horizon 2020 research and innovation program under grant agreement no 654148 Laserlab-Europe. This research project has been also supported 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.
KeyWords: ventricular-tachycardia; atrial-fibrillation; heart-failure; mouse hearts; in-vivo; excitation; arrhythmias; mechanisms; reentry; muscle
DOI: 10.1038/srep35628

Citations: 86
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