title: Optogenetics design of mechanistically-based stimulation patterns for cardiac defibrillation.
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.
authors.affiliation: European Laboratory for Non-Linear Spectroscopy, 50019 Sesto Fiorentino, Italy.|National Institute of Optics, National Research Council, 50125 Florence, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Crocini
authors.affiliation: Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ferrantini
authors.affiliation: Division of Pharmacology, Department "NeuroFarBa," University of Florence, 50139 Florence, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Coppini
authors.affiliation: European Laboratory for Non-Linear Spectroscopy, 50019 Sesto Fiorentino, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Scardigli
authors.affiliation: R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Yan
authors.affiliation: R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Loew
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Godfrey
authors.initials: G
authors.lastname: Smith
authors.affiliation: Division of Pharmacology, Department "NeuroFarBa," University of Florence, 50139 Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
authors.affiliation: Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Poggesi
authors.affiliation: European Laboratory for Non-Linear Spectroscopy, 50019 Sesto Fiorentino, Italy.|National Institute of Optics, National Research Council, 50125 Florence, Italy.|Department of Physics and Astronomy, University of Florence, 50019 Sesto Fiorentino, Italy.
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Pavone
authors.affiliation: European Laboratory for Non-Linear Spectroscopy, 50019 Sesto Fiorentino, Italy.|National Institute of Optics, National Research Council, 50125 Florence, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sacconi
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D000075402:Channelrhodopsins / Q000235:genetics*; D004195:Disease Models, Animal; D004554:Electric Countershock / Q000379:methods*; D004867:Equipment Design; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D051379:Mice; D062308:Optogenetics / Q000295:instrumentation*
chemical_list: D000075402:Channelrhodopsins