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 Lab Nonlinear Spect, I-50019 Sesto Fiorentino, Italy; CNR, Natl Opt Inst, I-50125 Florence, Italy; Univ Florence, Dept Expt & Clin Med, Div Physiol, I-50134 Florence, Italy; Univ Florence, Dept NeuroFarBa, Div Pharmacol, I-50139 Florence, Italy; Univ Connecticut, Ctr Hlth, RD Berlin Ctr Cell Anal & Modeling, Farmington, CT 06030 USA; Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland; Univ Florence, Dept Phys & Astron, I-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.

Journal/Review: SCIENTIFIC REPORTS

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: 87
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