Novel optics-based approaches for cardiac electrophysiology (original) (raw)
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Basic Concepts of Optical Mapping Techniques in Cardiac Electrophysiology
Biological Research For Nursing, 2009
Optical mapping is a tool used in cardiac electrophysiology to study the heart’s normal rhythm and arrhythmias. The optical mapping technique provides a unique opportunity to obtain membrane potential recordings with a higher temporal and spatial resolution than electrical mapping. Additionally, it allows simultaneous recording of membrane potential and calcium transients in the whole heart. This article presents the basic concepts of optical mapping techniques as an introduction for students and investigators in experimental laboratories unfamiliar with it.
Optical mapping of cardiac arrhythmias
Indian Pacing and Electrophysiology Journal, 2003
The concept of mapping rhythmic activation of the heart dates back to the beginning of last century, with initial descriptions of reentry in turtle hearts 1 , to the first systematic mapping of sinus rhythm and then atrial flutter by Lewis et al 2. Barker et al 3 were the first to map the human heart. Initial mapping was primarily performed using single probes to record activation in different regions of the heart. The 1960's and 70's saw the development of computerized mapping of the human heart, e.g. in the cure of Wolf-Parkinson-White syndrome as well as in the study of Langendorff preparations 4. In fact, most of the recent advances in cardiac mapping have focused on improvements in multisite recordings within the heart, with the ability to simultaneous record electrical activation from several hundreds of sites having contributed significantly to our understanding of atrial and ventricular arrhythmias. Despite these recent advances, multisite contact mapping suffers from several limitations, including the technical problems associated with amplification, gains, sampling rates, signal-tonoise ratio, and the inability to see signals during high-voltage shocks. In addition, an intrinsic limitation of current mapping techniques is their inability to provide information about repolarization characteristics of electrically active cells, thereby limiting our ability to study entire action potentials. In fact, intracellular microelectrode recordings are still considered the gold standard for the study of action potential characteristics in whole tissue. Microelectrode techniques are limited however, by an inability to record action potentials from several sites simultaneously, thereby precluding their use in high-density activation mapping. In part due to the above-mentioned limitations, the last few years have seen the development and use of voltage-sensitive dyes as a means to map not only activation, but repolarization as well. Voltage-sensitive dyes, when excited, provide an optical signal that mimics an action potential and thus allows the visualization of both activation and recovery processes in any region under view. This allows one to precisely evaluate the propagation of a wave of excitation and to measure its wavelength visually. Optical mapping techniques use imaging devices such as a photodiode array or a chargecoupled device video camera with the heart being illuminated and either continuously or spatially scanned. The basis for these techniques is the use of voltage-sensitive dyes that bind to or interact with cell membranes. Voltage-Sensitive Dyes Voltage-sensitive dyes are molecules that bind to the cell membrane with high affinity. While bound to the cardiac cell membrane, the dye molecules fluoresce light in direct proportion to transmembrane voltage. Therefore, voltage-sensitive dyes function as highly localized Rishi
Clinical Medicine Insights: Cardiology, 2016
Light has long been used to image the heart, but now it can be used to modulate its electrophysiological function. Imaging modalities and techniques have long constituted an indispensable part of arrhythmia research and treatment. Recently, advances in the fields of optogenetics and photodynamic therapy have provided scientists with more effective approaches for probing, studying and potentially devising new treatments for cardiac arrhythmias. This article is a review of research toward the application of these techniques. It contains (a) an overview of advancements in technology and research that have contributed to light-based cardiac applications and (b) a summary of current and potential future applications of light-based control of cardiac cells, including modulation of heart rhythm, manipulation of cardiac action potential morphology, quantitative analysis of arrhythmias, defibrillation and cardiac ablation.
Optical measurements of intramural action potentials in isolated porcine hearts using optrodes
Heart Rhythm, 2007
Background-Measurements of intramural V m would greatly increase knowledge of cardiac arrhythmias and defibrillation. Optrodes offer the possibility for three-dimensional V m mapping but their signal quality has been inadequate. Objectives-The objectives of this work were to improve optrode signal quality and use optrodes to measure intramural distribution of action potentials and shock-induced V m changes in porcine hearts. Methods-Optrodes were made from seven optical fibers 225 or 325 μm in diameter. Fiber ends were polished at 45° angle which improved light collection and allowed their insertion without a needle. Fluorescent measurements were performed in isolated porcine hearts perfused with Tyrode's solution or blood using V m-sensitive dye RH-237 and a 200-W Hg/Xe lamp. Results-The signal-to-noise ratio for 325-μm fibers was 44±23 in blood-perfused hearts (n=5) and 106±45 in Tyrode-perfused hearts (n=3), which represents a ≈4-fold improvement over previously reported data. There was close correspondence between optical and electrical measurements of activation times and action potential duration (APD). No significant intramural APD gradients were observed at cycle lengths up to 4 s and in the presence of dofetilide or d-sotalol. Application of shocks (5-50 V/cm) produced large intramural V m changes (up to ≈200%APA) possibly reflecting a combined effect of tissue discontinuities and optrode geometry. Conclusions-A substantial improvement of optrode signal quality was achieved. Optical measurements of APD and activation times matched electrical measurements. Optrode measurements revealed no significant intramural APD gradients. Application of shocks caused large intramural V m changes that could be influenced by the optrode geometry.
Pflügers Archiv - European Journal of Physiology, 2012
Whole-heart multi-parametric optical mapping has provided valuable insight into the interplay of electro-physiological parameters, and this technology will continue to thrive as dyes are improved and technical solutions for imaging become simpler and cheaper. Here, we show the advantage of using improved 2nd-generation voltage dyes, provide a simple solution to panoramic multiparametric mapping, and illustrate the application of flash photolysis of caged compounds for studies in the whole heart. For proof of principle, we used the isolated rat whole-heart model. After characterising the blue and green isosbestic points of di-4-ANBDQBS and di-4-ANBDQPQ, respectively, two voltage and calcium mapping systems are described. With two newly custommade multi-band optical filters, (1) di-4-ANBDQBS and fluo-4 and (2) di-4-ANBDQPQ and rhod-2 mapping are demonstrated. Furthermore, we demonstrate three-parameter mapping using di-4-ANBDQPQ, rhod-2 and NADH. Using off-the-shelf optics and the di-4-ANBDQPQ and rhod-2 combination, we demonstrate panoramic multi-parametric mapping, affording a 360°© spatiotemporal record of activity. Finally, local optical perturbation of calcium dynamics in the whole heart is demonstrated using the caged compound, o-nitrophenyl ethylene glycol tetraacetic acid (NP-EGTA), with an ultraviolet light-emitting diode (LED). Calcium maps (heart loaded with di-4-ANBDQPQ and rhod-2) demonstrate successful NP-EGTA loading and local flash photolysis. All imaging systems were built using only a single camera. In conclusion, using novel 2nd-generation voltage dyes, we developed scalable techniques for multi-parametric optical mapping of the whole heart from one point of view and panoramically. In addition to these parameter imaging approaches, we show that it is possible to use caged compounds and ultraviolet LEDs to locally perturb electrophysiological parameters in the whole heart.
Real-time optical manipulation of cardiac conduction in intact hearts
The Journal of Physiology
Although optogenetics has clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies lack the capability to react acutely to ongoing cardiac wave dynamics. r Here, we developed an all-optical platform to monitor and control electrical activity in real-time. r The methodology was applied to restore normal electrical activity after atrioventricular block and to manipulate the intraventricular propagation of the electrical wavefront. r The closed-loop approach was also applied to simulate a re-entrant circuit across the ventricle. r The development of this innovative optical methodology provides the first proof-of-concept that a real-time all-optical stimulation can control cardiac rhythm in normal and abnormal conditions.
In-Vivo Ratiometric Optical Mapping Enables High-Resolution Cardiac Electrophysiology in Pig Models
Cardiovascular Research
Aims Cardiac optical mapping is the gold standard for measuring complex electrophysiology in ex vivo heart preparations. However, new methods for optical mapping in vivo have been elusive. We aimed at developing and validating an experimental method for performing in vivo cardiac optical mapping in pig models. Methods and results First, we characterized ex vivo the excitation-ratiometric properties during pacing and ventricular fibrillation (VF) of two near-infrared voltage-sensitive dyes (di-4-ANBDQBS/di-4-ANEQ(F)PTEA) optimized for imaging blood-perfused tissue (n = 7). Then, optical-fibre recordings in Langendorff-perfused hearts demonstrated that ratiometry permits the recording of optical action potentials (APs) with minimal motion artefacts during contraction (n = 7). Ratiometric optical mapping ex vivo also showed that optical AP duration (APD) and conduction velocity (CV) measurements can be accurately obtained to test drug effects. Secondly, we developed a percutaneous dye-...