Iolanda Feola1, Linda Volkers1, Rupamanjari Majumder1, Alexander Teplenin1, Martin J Schalij1, Alexander V Panfilov1, Antoine A F de Vries1, Daniël A Pijnappels2. 1. From the Laboratory of Experimental Cardiology, Department of Cardiology, Heart Lung Center Leiden, Leiden University Medical Center, The Netherlands (I.F., L.V., R.M., A.T., M.J.S., A.V.P., A.A.F.d.V., D.A.P.); and Department of Physics and Astronomy, Ghent University, Belgium (A.V.P.). 2. From the Laboratory of Experimental Cardiology, Department of Cardiology, Heart Lung Center Leiden, Leiden University Medical Center, The Netherlands (I.F., L.V., R.M., A.T., M.J.S., A.V.P., A.A.F.d.V., D.A.P.); and Department of Physics and Astronomy, Ghent University, Belgium (A.V.P.). d.a.pijnappels@lumc.nl.
Abstract
BACKGROUND: Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers. METHODS AND RESULTS: Neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel (Ca2+-translocating channelrhodopsin) were subjected to patterned illumination to induce single, stable, and centralized rotors by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching any unexcitable boundary, did not lead to termination. Instead, electric waves started to propagate along the circumference of block, thereby maintaining reentrant activity, although of lower frequency. If, however, core-spanning lines of block reached at least 1 unexcitable boundary, reentrant activity was consistently terminated by wave collision. Lines of block away from the core region resulted merely in rotor destabilization (ie, drifting). CONCLUSIONS: Localized optogenetic targeting of rotors in atrial monolayers could lead to both stabilization and destabilization of reentrant activity. For termination, however, a line of block is required reaching from the core region to at least 1 unexcitable boundary. These findings may improve our understanding of the mechanisms involved in rotor-guided ablation.
BACKGROUND: Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers. METHODS AND RESULTS: Neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel (Ca2+-translocating channelrhodopsin) were subjected to patterned illumination to induce single, stable, and centralized rotors by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching any unexcitable boundary, did not lead to termination. Instead, electric waves started to propagate along the circumference of block, thereby maintaining reentrant activity, although of lower frequency. If, however, core-spanning lines of block reached at least 1 unexcitable boundary, reentrant activity was consistently terminated by wave collision. Lines of block away from the core region resulted merely in rotor destabilization (ie, drifting). CONCLUSIONS: Localized optogenetic targeting of rotors in atrial monolayers could lead to both stabilization and destabilization of reentrant activity. For termination, however, a line of block is required reaching from the core region to at least 1 unexcitable boundary. These findings may improve our understanding of the mechanisms involved in rotor-guided ablation.
Authors: Vasanth Ravikumar; Elizabeth Annoni; Preethy Parthiban; Sharon Zlochiver; Henri Roukoz; Siva K Mulpuru; Elena G Tolkacheva Journal: J Cardiovasc Electrophysiol Date: 2021-02-22
Authors: M Scardigli; C Müllenbroich; E Margoni; S Cannazzaro; C Crocini; C Ferrantini; R Coppini; P Yan; L M Loew; M Campione; L Bocchi; D Giulietti; E Cerbai; C Poggesi; G Bub; F S Pavone; L Sacconi Journal: J Physiol Date: 2018-08-07 Impact factor: 5.182
Authors: Rupamanjari Majumder; Iolanda Feola; Alexander V Panfilov; Daniel A Pijnappels; Alexander S Teplenin; Antoine Af de Vries Journal: Elife Date: 2018-09-27 Impact factor: 8.140
Authors: Christopher O'Shea; Andrew P Holmes; Ting Y Yu; James Winter; Simon P Wells; Joao Correia; Bastiaan J Boukens; Joris R De Groot; Gavin S Chu; Xin Li; G Andre Ng; Paulus Kirchhof; Larissa Fabritz; Kashif Rajpoot; Davor Pavlovic Journal: Sci Rep Date: 2019-02-04 Impact factor: 4.379