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Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers
- Source :
- Circulation: Arrhythmia and Electrophysiology, 10(11)
- Publication Year :
- 2017
-
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 (Ca 2+ -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.
- Subjects :
- 0301 basic medicine
Rhodopsin
Time Factors
cardiac
medicine.medical_treatment
Action Potentials
Catheter ablation
030204 cardiovascular system & hematology
Optogenetics
Transfection
03 medical and health sciences
0302 clinical medicine
Heart Rate
Physiology (medical)
catheter ablation
Medicine
Animals
atrial fibrillation
Heart Atria
myocytes, cardiac
Rats, Wistar
optogenetics
Cells, Cultured
Fibrillation
business.industry
Pulmonary vein ablation
voltage-sensitive dye imaging
ion channels
Atrial fibrillation
myocytes
gene transfer techniques
Ablation
medicine.disease
Cell biology
030104 developmental biology
Animals, Newborn
Calcium Channels
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Heart atrium
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Circulation: Arrhythmia and Electrophysiology, 10(11)
- Accession number :
- edsair.doi.dedup.....fbbc9d5e48f07e6ac8968e525026f82b