Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers

Feola, Iolanda; Volkers, Linda; Majumder, Rupamanjari; Teplenin, Alexander; Schalij, Martin J.; Panfilov, Alexander V.; Vries, Antoine A.F. de; Pijnappels, Daniël A.

doi:10.1161/circep.117.005591

Cited by 49 publications

(55 citation statements)

References 30 publications

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“…Using a reductionist cell monolayer approach, termination was found to require a line of conduction block reaching from the rotor core to at least 1 unexcitable boundary. 3 In contrast, incomplete conduction block merely provides a stable anchor for rotors to circulate about and perpetuate AF (Figure 1). Thus, providing critical insights into the mechanism(s) underlying procedural success for a novel ablation strategy that, to date, has met with variable outcomes.…”

Section: Atrial Arrhythmiasmentioning

confidence: 99%

Year in Review in Cardiac Electrophysiology

Tzou

Hussein

Madhavan

et al. 2018

Circ: Arrhythmia and Electrophysiology

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1 In the past year, there have been key advances in our understanding of arrhythmia mechanisms and diagnosis and important new therapies. We have seen advances in basic cardiac electrophysiology with demonstration of optogenetic targeting of atrial fibrillation (AF) rotors, induced pluripotent stem cell-based biological pacemakers, small-conductance Ca 2+ -activated K + (SK) channels as targets for AF treatment, and reductions in inward rectifier potassium current in promoting ventricular fibrillation. Hand-held ECG devices and implantable loop recorders have been shown to detect subclinical AF. Catheter ablation of AF in patients with left ventricular dysfunction improves outcomes compared with medical therapy. Both hybrid thoracoscopic surgical and catheter ablation procedures and off-pump surgery for AF have demonstrated efficacy. Anticoagulation with uninterrupted dabigatran had a lower major bleeding rate compared with uninterrupted warfarin after AF ablation. Studies have examined optimizing access to automatic external defibrillators by identifying optimal locations for placement and possibility of using a drone delivery network. In long-QT syndrome, there are advances in understanding of ECG predictors of arrhythmic events, the role of the role of gene variants in conferring arrhythmic risk, and effect of age and sex on QTc interval. There are numerous advances in the treatment of ventricular tachycardia, including noninvasive cardiac radiation. Catheter ablation and implantable devices continue to demonstrate effectiveness in patients with congenital heart disease.In the past year, there have been numerous ground-breaking discoveries and observations that illustrate the vibrancy and promise of our field. In this review, we have tried to capture articles published in the year 2017 of particular interest to cardiac electrophysiologists. Although we have focused on articles from our journal, we have captured many of the most impactful articles in numerous other journals. We apologize for omitting a large number of other important articles that cannot be included in this review because of space limitations. We have placed some of these in our Data Supplement. BASIC ELECTROPHYSIOLOGY BradyarrhythmiasThe search for new biological therapies for bradycardia met with recent progress as human keratinocytes genetically reprogrammed into electrically unstable cardiomyocytes were shown to persist and provide continued catecholaminergic-responsive pacing for 13 weeks after subepicardial injection into immunosuppressed dogs at the time of atrioventricular (AV) node ablation.1 Although only 40% to 80% of the beats matched the site of cell injection, this is first study to test a human induced pluripotent stem cell-based biological pacemaker in a large animal model of heart block and represents an important step forward in biological pacing.

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Section: Atrial Arrhythmiasmentioning

confidence: 99%

Year in Review in Cardiac Electrophysiology

Tzou

Hussein

Madhavan

et al. 2018

Circ: Arrhythmia and Electrophysiology

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“…a reversible conduction block) near the core of a spiral wave, and (ii) emergence of a wave from the spot of illumination. In a previous study ( Feola et al, 2017 ), we demonstrated the possibility to create such a temporal heterogeneity with optical control over the size, location and duration of the block. Here, we show how creation of a light-induced block close to the core of a spiral wave, can attract the spiral wave tip, causing it to eventually anchor to the block.…”

Section: Resultsmentioning

confidence: 99%

Optogenetics enables real-time spatiotemporal control over spiral wave dynamics in an excitable cardiac system

Majumder

Feola

Teplenin

et al. 2018

eLife

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Propagation of non-linear waves is key to the functioning of diverse biological systems. Such waves can organize into spirals, rotating around a core, whose properties determine the overall wave dynamics. Theoretically, manipulation of a spiral wave core should lead to full spatiotemporal control over its dynamics. However, this theory lacks supportive evidence (even at a conceptual level), making it thus a long-standing hypothesis. Here, we propose a new phenomenological concept that involves artificially dragging spiral waves by their cores, to prove the aforementioned hypothesis in silico, with subsequent in vitro validation in optogenetically modified monolayers of rat atrial cardiomyocytes. We thereby connect previously established, but unrelated concepts of spiral wave attraction, anchoring and unpinning to demonstrate that core manipulation, through controlled displacement of heterogeneities in excitable media, allows forced movement of spiral waves along pre-defined trajectories. Consequently, we impose real-time spatiotemporal control over spiral wave dynamics in a biological system.

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“…While previous studies by Feola et al ( 2017 ) and Majumder et al ( 2018 ) have proven that full spatio-temporal control over the dynamics of a spiral wave can be achieved by manipulating its core with supra-threshold illumination, the efficacy of their respective methods at sub-threshold illumination, remained untested. In this study, we exploited the power of regional sub-threshold illumination, to manipulate spiral wave dynamics with or without prior knowledge about the location of the spiral core.…”

Section: Discussionmentioning

confidence: 99%

Drift and termination of spiral waves in optogenetically modified cardiac tissue at sub-threshold illumination

Hussaini

Venkatesan

Uribe

et al. 2020

Preprint

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The development of new approaches to control cardiac arrhythmias requires a deep understanding of spiral wave dynamics. Optogenetics offers new possibilities for this. Preliminary experiments show that sub-threshold illumination affects electrical wave propagation in the mouse heart. However, a systematic exploration of these effects is technically challenging. Here, we use state-of-the-art computer models to study the dynamic control of spiral waves in a two-dimensional model of the adult mouse ventricle, using stationary and non-stationary patterns of sub-threshold illumination. Our results indicate a light intensity-dependent increase in cellular resting membrane potentials, which together with diffusive cell-cell coupling leads to the development of spatial voltage gradients over differently illuminated areas. A spiral wave drifts along the positive gradient. These gradients can be strategically applied to ensure drift-induced termination of a spiral wave, both in optogenetics and in conventional methods of electrical defibrillation.

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Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers

Cited by 49 publications

References 30 publications

Year in Review in Cardiac Electrophysiology

Year in Review in Cardiac Electrophysiology

Optogenetics enables real-time spatiotemporal control over spiral wave dynamics in an excitable cardiac system

Drift and termination of spiral waves in optogenetically modified cardiac tissue at sub-threshold illumination

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