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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.
Keywords
PULMONARY-VEIN ABLATION, CATHETER ABLATION, RHYTHM MANAGEMENT, IN-VITRO, FIBRILLATION, HEART, ARRHYTHMIAS, TRIAL, TERMINATION, MODULATION, atrial fibrillation, catheter ablation, gene transfer techniques, ion, channels, myocytes, cardiac, optogenetics, voltage-sensitive dye imaging

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Citation

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MLA
Feola, Iolanda, Linda Volkers, Rupamanjari Majumder, et al. “Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers.” CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY 10.11 (2017): n. pag. Print.
APA
Feola, I., Volkers, L., Majumder, R., Teplenin, A., Schalij, M. J., Panfilov, A., de Vries, A. A., et al. (2017). Localized optogenetic targeting of rotors in atrial cardiomyocyte monolayers. CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, 10(11).
Chicago author-date
Feola, Iolanda, Linda Volkers, Rupamanjari Majumder, Alexander Teplenin, Martin J Schalij, Alexander Panfilov, Antoine AF de Vries, and Daniel A Pijnappels. 2017. “Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers.” Circulation-arrhythmia and Electrophysiology 10 (11).
Chicago author-date (all authors)
Feola, Iolanda, Linda Volkers, Rupamanjari Majumder, Alexander Teplenin, Martin J Schalij, Alexander Panfilov, Antoine AF de Vries, and Daniel A Pijnappels. 2017. “Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers.” Circulation-arrhythmia and Electrophysiology 10 (11).
Vancouver
1.
Feola I, Volkers L, Majumder R, Teplenin A, Schalij MJ, Panfilov A, et al. Localized optogenetic targeting of rotors in atrial cardiomyocyte monolayers. CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY. 2017;10(11).
IEEE
[1]
I. Feola et al., “Localized optogenetic targeting of rotors in atrial cardiomyocyte monolayers,” CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, vol. 10, no. 11, 2017.
@article{8565131,
  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.},
  articleno    = {e005591},
  author       = {Feola, Iolanda and Volkers, Linda and Majumder, Rupamanjari and Teplenin, Alexander and Schalij, Martin J and Panfilov, Alexander and de Vries, Antoine AF and Pijnappels, Daniel A},
  issn         = {1941-3149},
  journal      = {CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY},
  keywords     = {PULMONARY-VEIN ABLATION,CATHETER ABLATION,RHYTHM MANAGEMENT,IN-VITRO,FIBRILLATION,HEART,ARRHYTHMIAS,TRIAL,TERMINATION,MODULATION,atrial fibrillation,catheter ablation,gene transfer techniques,ion,channels,myocytes,cardiac,optogenetics,voltage-sensitive dye imaging},
  language     = {eng},
  number       = {11},
  pages        = {13},
  title        = {Localized optogenetic targeting of rotors in atrial cardiomyocyte monolayers},
  url          = {http://dx.doi.org/10.1161/CIRCEP.117.005591},
  volume       = {10},
  year         = {2017},
}

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