Optogenetics for in vivo cardiac pacing and resynchronization therapies

@article{Nussinovitch2015OptogeneticsFI,
  title={Optogenetics for in vivo cardiac pacing and resynchronization therapies},
  author={U. Nussinovitch and L. Gepstein},
  journal={Nature Biotechnology},
  year={2015},
  volume={33},
  pages={750-754}
}
Abnormalities in the specialized cardiac conduction system may result in slow heart rate or mechanical dyssynchrony. [...] Key Result We used adeno-associated virus (AAV) 9 to express the Channelrhodopsin-2 (ChR2) transgene at one or more ventricular sites in rats. This allowed optogenetic pacing of the hearts at different beating frequencies with blue-light illumination both in vivo and in isolated perfused hearts.Expand
Optogenetics for cardiac pacing, resynchronization, and arrhythmia termination
TLDR
Following a general introduction to optotools and gene transfer to the heart, these applications of optogenetics will be discussed in this chapter from mechanistic and translational points of view and a critical assessment of its clinical perspective is outlined. Expand
Optogenetic approaches for termination of ventricular tachyarrhythmias after myocardial infarction in rats in vivo.
TLDR
It is demonstrated that optogenetic-based cardioversion is feasible and effective in vivo, with the underlying mechanism involving the light-triggered, ChR2-induced depolarization of the illuminated myocardium, in turn generating an excitation that disrupts the pre-existing re-entrant wavefront. Expand
Optogenetic termination of ventricular arrhythmias in the whole heart: towards biological cardiac rhythm management
TLDR
Local epicardial illumination of the optogenetically modified adult rat heart allows contact- and shock-free termination of ventricular arrhythmia termination in an effective and repetitive manner after optogenetic modification. Expand
Cardiac pacing using transmural multi-LED probes in channelrhodopsin-expressing mouse hearts
TLDR
It is demonstrated that IMLOP insertion needs approximately 20 mN of force, limiting possible damage from excessive loads applied during implantation, and in situ experiments on ChR2-expressing mouse hearts demonstrated that optical stimulation is possible with light intensities as low as 700 μW/mm2; although stable pacing requires higher intensities. Expand
Optogenetic Termination of Cardiac Arrhythmia: Mechanistic Enlightenment and Therapeutic Application?
TLDR
This review gives a concise introduction to optogenetic stimulation of cardiomyocytes and the whole heart and summarize the recent progress on optogenetics defibrillation and cardioversion to terminate cardiac arrhythmia. Expand
Cardiac optogenetics: a decade of enlightenment
TLDR
A decade of advances based on all-optical electrophysiology is appraised, including high-throughput screening, cardiotoxicity testing and personalized medicine assays, and long-term (aspirational) prospects for clinical translation of cardiac optogenetics, including new optical therapies for rhythm control. Expand
Energy-Reduced Arrhythmia Termination Using Global Photostimulation in Optogenetic Murine Hearts
TLDR
The results show that by tuning the light intensity without exceeding 1.10 mW mm-2, a single pulse in the range of 10–1,000 ms is sufficient to reliably reset the heart into sinus rhythm, and can be modules in the design of novel illumination technologies with specific energy requirements on the way toward tissue-protective defibrillation techniques. Expand
Cardiac optogenetics: the next frontier
  • Amit Gruber, Oded Edri, L. Gepstein
  • Medicine
  • Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
  • 2018
TLDR
The ability to control (augment or suppress) the cardiac tissue's excitable properties using optogenetic actuators (microbial opsins), which are light-gated ion channels and pumps that can cause light-triggered membrane depolarization or hyperpolarization is discussed. Expand
Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations.
TLDR
The results demonstrate that optogenetic defibrillation is highly effective in the mouse heart and could potentially be translated into humans to achieve nondamaging and pain-free termination of ventricular arrhythmia. Expand
Cardiac Optogenetics: 2018.
TLDR
This review summarizes developments achieved since the inception of cardiac optogenetics research, which has spanned nearly a decade, and provides an overview of recent methodological advances in opsin engineering, light sensitization of cardiac tissue, strategies for illuminating the heart, and frameworks for simulatingoptogenetics in realistic computational models of patient hearts. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 27 REFERENCES
Modulation of cardiac tissue electrophysiological properties with light-sensitive proteins.
TLDR
The results of this proof-of-concept study highlight the unique potential of optogenetics for future biological pacemaking and resynchronization therapy applications and for the development of novel anti-arrhythmic strategies. Expand
Optogenetic control of heart muscle in vitro and in vivo
Electrical stimulation is the standard technique for exploring electrical behavior of heart muscle, but this approach has considerable technical limitations. Here we report expression of theExpand
Optogenetic Control of Cardiac Function
TLDR
These studies combine optogenetics and light-sheet microscopy to reveal the emergence of organ function during development. Expand
Stimulating Cardiac Muscle by Light: Cardiac Optogenetics by Cell Delivery
TLDR
The utility of optogenetics to cardiac muscle is demonstrated by a tandem cell unit (TCU) strategy, in which nonexcitable cells carry exogenous light-sensitive ion channels, and, when electrically coupled to cardiomyocytes, produce optically excitable heart tissue. Expand
Biological Pacemaker Implanted in Canine Left Bundle Branch Provides Ventricular Escape Rhythms That Have Physiologically Acceptable Rates
TLDR
A gene-therapy approach for induction of biological pacemaker activity within the LBB system provides ventricular escape rhythms that have physiologically acceptable rates. Expand
A comprehensive multiscale framework for simulating optogenetics in the heart
TLDR
A comprehensive framework for multi-scale modelling of cardiac optogenetics is presented, allowing both mechanistic examination of optical control and exploration of potential therapeutic applications, and making possible the prediction of emergent behaviour resulting from interactions at sub-organ scales. Expand
Biological therapies for cardiac arrhythmias: can genes and cells replace drugs and devices?
TLDR
The state of the art in gene- and cell-based therapies to correct cardiac rhythm disturbances is reviewed, with insights gained bringing the field closer to a paradigm shift away from devices and drugs, and toward biologics, in the treatment of rhythm disorders. Expand
Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18
TLDR
Conversion of rodent cardiomyocytes to SAN cells in vitro and in vivo by expression of Tbx18, a gene critical for early SAN specification is demonstrated, opening new prospects for bioengineered pacemakers. Expand
The road to biological pacing
TLDR
This Review revisits certain milestones achieved through the construction of a 'roadmap' in biological pacing and suggests that the next decade should see either biological pacemakers become a clinical reality or the improvement of electronicpacemakers to a point where the biological approach is no longer a viable alternative. Expand
Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure.
TLDR
In patients with advanced heart failure and a prolonged QRS interval, cardiac-resynchronization therapy decreases the combined risk of death from any cause or first hospitalization and, when combined with an implantable defibrillator, significantly reduces mortality. Expand
...
1
2
3
...