Optical mapping of electrical heterogeneities in the heart during global ischemia (original) (raw)
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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-...
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
American Journal of Physiology-Heart and Circulatory Physiology, 2007
Our objective was to establish a novel model for the study of ventricular fibrillation (VF) in humans. We adopted the established techniques of optical mapping to human ventricles for the first time to determine whether human VF is the result of wave breaks and singularity point formation and is maintained by high-frequency rotors and fibrillatory conduction. We describe the technique of acquiring optical signals in human hearts during VF, their characteristics, and the feasibility of possible analyses that could be performed to elucidate mechanisms of human VF. We used explanted hearts from five cardiomyopathic patients who underwent transplantation. The hearts were Langendorff perfused with Tyrode solution (95% O2-5% CO2), and the potentiometric dye di-4-ANEPPS was injected as a bolus into the coronary circulation. Fluorescence was excited at 531 ± 20 nm with a 150-W halogen light source; the emission signal was long-pass filtered at 610 nm and recorded with a mapping camera. Frac...
In Situ Optical Mapping of Voltage and Calcium in the Heart
PLoS ONE, 2012
Electroanatomic mapping the interrelation of intracardiac electrical activation with anatomic locations has become an important tool for clinical assessment of complex arrhythmias. Optical mapping of cardiac electrophysiology combines high spatiotemporal resolution of anatomy and physiological function with fast and simultaneous data acquisition. If applied to the clinical setting, this could improve both diagnostic potential and therapeutic efficacy of clinical arrhythmia interventions. The aim of this study was to explore this utility in vivo using a rat model. To this aim, we present a singlecamera imaging and multiple light-emitting-diode illumination system that reduces economic and technical implementation hurdles to cardiac optical mapping. Combined with a red-shifted calcium dye and a new near-infrared voltage-sensitive dye, both suitable for use in blood-perfused tissue, we demonstrate the feasibility of in vivo multiparametric imaging of the mammalian heart. Our approach combines recording of electrophysiologically-relevant parameters with observation of structural substrates and is adaptable, in principle, to trans-catheter percutaneous approaches.
PloS one, 2015
Because of the optical features of heart tissue, optical and electrical action potentials are only moderately associated, especially when near-infrared dyes are used in optical mapping (OM) studies. By simultaneously recording transmural electrical action potentials (APs) and optical action potentials (OAPs), we aimed to evaluate the contributions of both electrical and optical influences to the shape of the OAP upstroke. A standard glass microelectrode and OM, using an near-infrared fluorescent dye (di-4-ANBDQBS), were used to simultaneously record transmural APs and OAPs in a Langendorff-perfused rabbit heart during atrial, endocardial, and epicardial pacing. The actual profile of the transmural AP upstroke across the LV wall, together with the OAP upstroke, allowed for calculations of the probing-depth constant (k ~2.1 mm, n = 24) of the fluorescence measurements. In addition, the transmural AP recordings aided the quantitative evaluation of the influences of depth-weighted and l...
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.
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.
The Design and Use of an Optical Mapping System for the Study of Intracardiac Electrical Signaling
Indian Pacing and Electrophysiology Journal, 2012
Fluorescent optical mapping of electrically active cardiac tissues provides a unique method to examine the excitation wave dynamics of underlying action potentials. Such mapping can be viewed as a bridge between cellular level and organ systems physiology, e.g., by facilitating the development of advanced theoretical concepts of arrhythmia. We present the design and use of a high-speed, high-resolution optical mapping system composed entirely of "off the shelf" components. The electrical design integrates a 256 element photodiode array with a 16 bit data acquisition system. Proper grounding and shielding at various stages of the design reduce electromagnetic interference. Our mechanical design provides flexibility in terms of mounting positions and applications (use for whole heart or tissue preparations), while maintaining precise alignment between all optical components. The system software incorporates a user friendly graphical user interface, e.g., spatially recorded action potentials can be represented as intensity graphs or in strip chart format. Thus, this system is capable of displaying cardiac action potentials with high spatiotemporal resolution. Results from cardiac action potential mapping with intact mouse hearts are provided. It should be noted that this system could be readily configured to study isolated myocardial biopsies (e.g., isolated ventricular trabeculae). We describe the details of a versatile, user-friendly system that could be employed for a magnitude of study protocols.
Frontiers in Physiology, 2014
To investigate the dynamics and propensity for arrhythmias in intact transgenic hearts comprehensively, optical strategies for panoramic fluorescence imaging of action potential (AP) propagation are essential. In particular, mechanism-oriented molecular studies usually depend on transgenic mouse hearts of only a few millimeters in size. Furthermore, the temporal scales of the mouse heart remain a challenge for panoramic fluorescence imaging with heart rates ranging from 200 min −1 (e.g., depressed sinus node function) to over 1200 min −1 during fast arrhythmias. To meet these challenging demands, we and others developed physiologically relevant mouse models and characterized their hearts with planar AP mapping. Here, we summarize the progress toward panoramic fluorescence imaging and its prospects for the mouse heart. In general, several high-resolution cameras are synchronized and geometrically arranged for panoramic voltage mapping and the surface and blood vessel anatomy documented through image segmentation and heart surface reconstruction. We expect that panoramic voltage imaging will lead to novel insights about molecular arrhythmia mechanisms through quantitative strategies and organ-representative analysis of intact mouse hearts. Citation: Dura M, Schröder-Schetelig J, Luther S and Lehnart SE (2014) Toward panoramic in situ mapping of action potential propagation in transgenic hearts to investigate initiation and therapeutic control of arrhythmias. Front. Physiol. 5:337.