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In JoVE (1)
Other Publications (35)
- Circulation Research
- Biophysical Journal
- Journal of Cardiovascular Electrophysiology
- Physical Review Letters
- Studies in Health Technology and Informatics
- Circulation Research
- Cardiovascular Research
- Circulation Research
- 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
- Cardiovascular Research
- American Journal of Physiology. Heart and Circulatory Physiology
- Systematic Parasitology
- Systematic Parasitology
- Journal of Biomedical Optics
- Physics in Medicine and Biology
- The Journal of Physiology
- American Journal of Physiology. Heart and Circulatory Physiology
- American Journal of Physiology. Heart and Circulatory Physiology
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- Circulation Research
- Proceedings of the National Academy of Sciences of the United States of America
- Circulation
- Circulation. Arrhythmia and Electrophysiology
- Applied Optics
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- Systematic Parasitology
- Biophysical Journal
- 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
- Circulation Research
- Cardiovascular Research
- The Journal of Physiology
- Systematic Parasitology
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- Cardiovascular Research
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Articles by Sergey Mironov in JoVE
JoVE Clinical and Translational Medicine
Высокого разрешения эндокарда и эпикарда Оптический отображения в Овцы модели из стрейч-индуцированной фибрилляции предсердий
Center for Arrhythmia Research. Internal Medicine, University of Michigan
В настоящем докладе содержится подробное описание методологии и результатов одновременных эндокарда и эпикарда оптических отображение электрического возбуждения в интактном левое предсердие из Langendorff-перфузии овец сердца во время стретч-индуцированной фибрилляции предсердий.
Other articles by Sergey Mironov on PubMed
Frequency-dependent Breakdown of Wave Propagation into Fibrillatory Conduction Across the Pectinate Muscle Network in the Isolated Sheep Right Atrium
Atrial fibrillation (AF) may result from stationary reentry in the left atrium (LA), with fibrillatory conduction toward the right atrium (RA). We hypothesize that periodic input to the RA at an exceedingly high frequency results in disorganized wave propagation, compatible with fibrillatory conduction. Simultaneous endocardial and epicardial optical mapping (di-4-ANEPPS) was performed in isolated, coronary-perfused sheep RA. Rhythmic pacing of Bachmann's bundle allowed well-controlled and realistic conditions for LA-driven RA. Pacing at increasingly higher frequencies (2.0 to 6.0 Hz) led to increasing delays in activation distal to major branching sites of the crista terminalis and pectinate bundles, culminating in spatially distributed intermittent blockade at or above approximately 6.5 Hz. At this "breakdown frequency," the direction of RA propagation became completely variable from beat to beat and thus transformed into fibrillatory conduction. Such frequency-dependent changes were independent of action potential duration. Rather, the spatial boundaries between proximal and distal frequencies correlated well with branch sites of the pectinate musculature. Thus, there exists a breakdown frequency in the sheep RA below which activity is periodic throughout the atrium and above which it is fibrillation-like. The data are consistent with the ideas that during AF, high-frequency activation initiated in the LA undergoes fibrillatory conduction toward the RA, and that sink-to-source effect at branch points of the crista terminalis and pectinate muscles is important in determining the complexity of the arrhythmia.
Synthesis of Voltage-sensitive Fluorescence Signals from Three-dimensional Myocardial Activation Patterns
Voltage-sensitive fluorescent dyes are commonly used to measure cardiac electrical activity. Recent studies indicate, however, that optical action potentials (OAPs) recorded from the myocardial surface originate from a widely distributed volume beneath the surface and may contain useful information regarding intramural activation. The first step toward obtaining this information is to predict OAPs from known patterns of three-dimensional (3-D) electrical activity. To achieve this goal, we developed a two-stage model in which the output of a 3-D ionic model of electrical excitation serves as the input to an optical model of light scattering and absorption inside heart tissue. The two-stage model permits unique optical signatures to be obtained for given 3-D patterns of electrical activity for direct comparison with experimental data, thus yielding information about intramural electrical activity. To illustrate applications of the model, we simulated surface fluorescence signals produced by 3-D electrical activity during epicardial and endocardial pacing. We discovered that OAP upstroke morphology was highly sensitive to the transmural component of wave front velocity and could be used to predict wave front orientation with respect to the surface. These findings demonstrate the potential of the model for obtaining useful 3-D information about intramural propagation.
Delayed Success in Termination of Three-dimensional Reentry: Role of Surface Polarization
Defibrillation shocks slightly stronger than cardioversion threshold may defibrillate not immediately but after a transient period of postshock activity (delayed success). The effect of a defibrillation shock is that it polarizes the tissue, primarily at the surfaces; therefore, surface polarization may play an important role at near-threshold shock intensities.
Intermittent Self-organization of Scroll Wave Turbulence in Three-dimensional Excitable Media
We study the asymptotic behavior of scroll wave turbulence in large three-dimensional excitable media modeled by FitzHugh-Nagumo equations. The focus is on the type of turbulence caused by negative tension of scroll wave filaments, which is considered to be one of the mechanisms of cardiac fibrillation. We discovered that the initial increase in turbulence complexity can be followed by intermittent self-organization, when complex filament tangles are replaced by a small number of relatively stable triple filament strands. The intermittency is the result of a competition between the destabilizing effect of negative tension and mutual attraction of filaments with similar orientation.
Telemedicine in Russia
There are quite a number of the Russian medical institutions using different telemedicine technologies. There are also several telehealth networks created around the scientific medical centers and large hospitals. They use store-and-forward technology and real-time video conferencing over ISDN and IP-channels. Quality issues, management and legal issues, integration and financing issues, future development of the Russian telehealth networks are discussed.
Epicardial Fiber Organization in Swine Right Ventricle and Its Impact on Propagation
Fiber organization is important for myocardial excitation and contraction. It can be a major factor in arrhythmogenesis and current distribution during defibrillation shocks. In this study, we report the discovery of a previously undetected thin epicardial layer in swine right ventricle (RV) with distinctly different fiber orientation, which significantly affects epicardial propagation. Experiments were conducted in isolated coronary-perfused right ventricular free wall preparations (n=8) stained with the voltage-sensitive dye di-4-ANEPPS. Optical signals were recorded from the epicardium with a CCD video camera at 800 fps. Preparations were sectioned parallel to the epicardial surface with a resolution of 50 mum or better. To link the histological data with the observed activation patterns, resulting fiber angles were introduced into a 3D computer model to simulate the electrical activation and voltage-dependent optical signals. In all preparations, we detected a thin epicardial layer with almost no depth-dependent fiber rotation. The thickness of this layer (z(0)) varied from 110 to 930 microm. At the boundary of this layer, we observed an abrupt change in fiber angle by 64+/-13 degrees followed by a gradual fiber rotation in the underlying layers. In preparations with z(0) <700 microm, optical mapping during epicardial stimulation revealed unusual diamond- and rectangular-shaped activation fronts with two axes of fast conduction. Computer simulations accurately predicted the features of the experimentally recorded activation fronts. The free wall of swine RV has a thin epicardial layer with distinctly different fiber orientation, which can significantly affect propagation and give rise to unusually shaped activation fronts. This is important for understanding electrical propagation in the heart, and further refines the existing knowledge of myocardial fiber architecture.
Effect of Remodelling, Stretch and Ischaemia on Ventricular Fibrillation Frequency and Dynamics in a Heart Failure Model
The dynamics of ventricular fibrillation (VF) in the presence of heart failure (HF) are different from those in the normal heart. This has been attributed solely to HF-induced electrophysiologic remodelling. We hypothesized that acute stretch and ischaemia, which are normally present during VF, might contribute significantly to the altered VF dynamics in HF.
Optical Action Potential Upstroke Morphology Reveals Near-surface Transmural Propagation Direction
The analysis of surface-activation patterns and measurements of conduction velocity in ventricular myocardium is complicated by the fact that the electrical wavefront has a complex 3D shape and can approach the heart surface at various angles. Recent theoretical studies suggest that the optical upstroke is sensitive to the subsurface orientation of the wavefront. Our goal here was to (1) establish the quantitative relationship between optical upstroke morphology and subsurface wavefront orientation using computer modeling and (2) test theoretical predictions experimentally in isolated coronary-perfused swine right ventricular preparations. We show in numerical simulations that by suitable placement of linear epicardial stimulating electrodes, the angle phi of wavefronts with respect to the heart surface can be controlled. Using this method, we developed theoretical predictions of the optical upstroke shape dependence on phi. We determined that the level VF* at which the rate of rise of the optical upstroke reaches the maximum linearly depends on phi. A similar relationship was found in simulations with epicardial point stimulation. The optical mapping data were in good agreement with theory. Plane waves propagating parallel to myocardial fibers produced upstrokes with VF*<0.5, consistent with theoretical predictions for phi>0. Similarly, we obtained good agreement with theory for plane waves propagating in a direction perpendicular to fibers (VF*>0.5 when phi<0). Finally, during epicardial point stimulation, we discovered characteristic saddle-shaped VF* maps that were in excellent agreement with theoretically predicted changes in phi during wavefront expansion. Our findings should allow for improved interpretation of the results of optical mapping of intact heart preparations.
Alternating Conduction in the Ischaemic Border Zone As Precursor of Reentrant Arrhythmias: a Simulation Study
Here, we investigate the mechanisms underlying the onset of conduction-related arrhythmias in a three-dimensional (3D) computational model of acute regional ischaemia.
Near-threshold Field Stimulation: Intramural Versus Surface Activation
The mechanism by which an electric field terminates arrhythmias continues to puzzle investigators. Existing experimental methods provide information about epicardial manifestations of electrical cardioversion, yet little is known about field effects deep inside the myocardium. Here we combine specially designed optical mapping experiments and computer modeling to separate the intra-myocardial and surface field effects.
Fluorescence Imaging of Cardiac Propagation: Spectral Properties and Filtering of Optical Action Potentials
Fluorescence imaging using voltage-sensitive dyes is an important tool for studying electrical propagation in the heart. Yet, the low amplitude of the voltage-sensitive component in the fluorescence signal and high acquisition rates dictated by the rapid propagation of the excitation wave front make it difficult to achieve recordings with high signal-to-noise ratios. Although spatially and temporally filtering the acquired signals has become de facto one of the key elements of optical mapping, there is no consensus regarding their use. Here we characterize the spatiotemporal spectra of optically recorded action potentials and determine the distortion produced by conical filters of different sizes. On the basis of these findings, we formulate the criteria for rational selection of filter characteristics. We studied the evolution of the spatial spectra of the propagating wave front after epicardial point stimulation of the isolated, perfused right ventricular free wall of the pig heart stained with di-4-ANEPPS. We found that short-wavelength (<3 mm) spectral components represent primarily noise and surface features of the preparation (coronary vessels, fat, and connective tissue). The time domain of the optical action potential spectrum also lacks high-frequency components (>100 Hz). Both findings are consistent with the reported effect of intrinsic blurring caused by light scattering inside the myocardial wall. The absence of high-frequency spectral components allows the use of aggressive low-pass spatial and temporal filters without affecting the optical action potential morphology. We show examples where the signal-to-noise ratio increased up to 150 with <3% distortion. A generalization of our approach to the rational filter selection in various applications is discussed.
Four New Species of the Feather Mite Genus Vanginyssus Mironov, 2001 (Astigmata: Pteronyssidae) from the Vangas (Passeriformes: Vangidae) in Madagascar
Four new feather mite species of Vanginyssus Mironov, 2001 are described from vangas (Passeriformes: Vangidae), an endemic passerine family from Madagascar: Vanginyssus euryceros n. sp. from the helmet vanga Euryceros prevostii Lesson, V. madagascarinus n. sp. from the blue vanga Cyanolanius madagascarinus (Linnaeus), V. mystacornis n. sp. from the Crossley's babbler Mystacornis crossleyi (Grandidier) and V. orioliae n. sp. from the Bernier's vanga Oriolia bernieri Geoffroy Saint-Hilaire. A key to the five known species of Vanginyssus is provided.
Revision of the Genus Galagocheles Fain (Acari: Cheyletidae), Parasites of Galagos (Primates: Galagonidae)
Galagocheles Fain, 1979 (Acari: Cheyletidae), comprising permanent parasites of African prosimian primates (Galagonidae), is revised. An amended diagnosis of the genus based on characters of adults and immatures is given. The type-species, G. lemuricola (Lawrence, 1948), from Otolemur garnetti (Ogilby) (type-host) and O. crassicaudatus Geoffroy, is redescribed, and G. lawrencei n. sp. is described from Galago senegalensis Geoffroy (type-host) and G. moholi Smith. The new species differs from G. lemuricola by its smaller body size, the obtuse posterior end of the opisthosoma in males, and by fine, nude setae ps3 in females. The systematics of the cheyletid tribe Niheliini and host-parasite associations of its species are briefly discussed. The tribe Criokerontini is included to the tribe Niheliini. It is suggested that the ancestors of the tribe Niheliini were predaceous cheyletids associated with the nests of arboreal mammals, and the association of Nihelia spp. on mongooses (Herpestidae) is the result of the host-switching from some ancient arboreal mammal.
Method for the Three-dimensional Localization of Intramyocardial Excitation Centers Using Optical Imaging
This study explores the possibility of localizing the excitation centers of electrical waves inside the heart wall using voltage-sensitive dyes (fluorescent or absorptive). In the present study, we propose a method for the 3-D localization of excitation centers from pairs of 2-D images obtained in two modes of observation: reflection and transillumination. Such images can be obtained using high-speed charge-coupled device (CCD) cameras and photodiode arrays with time resolution up to 0.5 ms. To test the method, we simulate optical signals produced by point sources and propagating ellipsoidal waves in 1-cm-thick slabs of myocardial tissue. Solutions of the optical diffusion equation are constructed by employing the method of images with Robin boundary conditions. The coordinates of point sources as well as of the centers of expanding waves can be accurately determined using the proposed algorithm. The method can be extended to depth estimations of the outer boundaries of the expanding wave. The depth estimates are based on ratios of spatially integrated images. The method shows high tolerance to noise and can give accurate results even at relatively low signal-to-noise ratios. In conclusion, we propose a novel and efficient algorithm for the localization of excitation centers in 3-D cardiac tissue.
Multiplicative Optical Tomography of Cardiac Electrical Activity
Cardiac electrical activity can be mapped today through the response of voltage-sensitive dyes; but poor transparency of muscle tissue has enforced shallow-depth imaging. We present a three-dimensional (3D) reconstruction method for electrical activity deep inside the myocardial wall. Our approach is nonlinear and differs substantially from standard diffusive optical tomography. It does not require matrix inversion, data regularization or a priori information concerning the original object. Opposite sides of a slab-shaped preparation are scanned in parallel by detection and illumination points with a constant vector offset between illumination and detection axes (biaxial scanning). Scanning is performed in two perpendicular directions. In each direction, a pair of 2D images is obtained under offsets of opposite signs. These two pairs are the input for a multiplicative reconstruction algorithm, whose output is a 3D image. The overall procedure was successfully tested on computer-generated sources that include points, lines and hemispheres, patterned after actual electrophysiological excitations. The algorithm is computationally efficient and stable with respect to varying noise levels in the raw data.
Up-regulation of the Inward Rectifier K+ Current (I K1) in the Mouse Heart Accelerates and Stabilizes Rotors
Previous studies have suggested an important role for the inward rectifier K+ current (I K1) in stabilizing rotors responsible for ventricular tachycardia (VT) and fibrillation (VF). To test this hypothesis, we used a line of transgenic mice (TG) overexpressing Kir 2.1-green fluorescent protein (GFP) fusion protein in a cardiac-specific manner. Optical mapping of the epicardial surface in ventricles showed that the Langendorff-perfused TG hearts were able to sustain stable VT/VF for 350 +/- 1181 s at a very high dominant frequency (DF) of 44.6 +/- 4.3 Hz. In contrast, tachyarrhythmias in wild-type hearts (WT) were short-lived (3 +/- 9 s), and the DF was 26.3 +/- 5.2 Hz. The stable, high frequency, reentrant activity in TG hearts slowed down, and eventually terminated in the presence of 10 mum Ba2+, suggesting an important role for I K1. Moreover, by increasing I K1 density in a two-dimensional computer model having realistic mouse ionic and action potential properties, a highly stable, fast rotor (approximately 45 Hz) could be induced. Simulations suggested that the TG hearts allowed such a fast and stable rotor because of both greater outward conductance at the core and shortened action potential duration in the core vicinity, as well as increased excitability, in part due to faster recovery of Na+ current. The latter resulted in a larger rate of increase in the local conduction velocity as a function of the distance from the core in TG compared to WT hearts, in both simulations and experiments. Finally, simulations showed that rotor frequencies were more sensitive to changes (doubling) in I K1, compared to other K+ currents. In combination, these results provide the first direct evidence that I K1 up-regulation in the mouse heart is a substrate for stable and very fast rotors.
Optical Mapping of Langendorff-perfused Human Hearts: Establishing a Model for the Study of Ventricular Fibrillation in Humans
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% O(2)-5% CO(2)), 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. Fractional change of fluorescence varied between 2% and 12%. Average signal-to-noise ratio was 40 dB. The mean velocity of VF wave fronts was 0.25 +/- 0.04 m/s. Submillimetric spatial resolution (0.65-0.85 mm), activation mapping, and transformation of the data to phase-based analysis revealed reentrant, colliding, and fractionating wave fronts in human VF. On many occasions the VF wave fronts were as large as the entire vertical length (8 cm) of the mapping field, suggesting that there are a limited number of wave fronts on the human heart during VF. Phase transformation of the optical signals allowed the first demonstration ever of phase singularity point, wave breaks, and rotor formation in human VF. This method provides opportunities for potential analyses toward elucidation of the mechanisms of VF and defibrillation in humans.
Three Distinct Phases of VF During Global Ischemia in the Isolated Blood-perfused Pig Heart
Changes in ventricular fibrillation (VF) organization occurring after the onset of global ischemia are relevant to defibrillation and survival but remain poorly understood. We hypothesized that ischemia-specific dynamic instability of the action potential (AP) causes a loss of spatiotemporal periodicity of propagation and broadening of the electrocardiogram (ECG) frequency spectrum during VF in the ischemic myocardium. We recorded voltage-sensitive fluorescence of di-4-ANEPPS (anterior left ventricle, 35 x 35 mm, 64 x 64 pixels) and the volume-conducted ECG in six blood-perfused hearts during 10 min of VF and global ischemia. We used coefficient of variation (CV) to estimate variability of AP amplitude, AP duration, and diastolic interval (CV-APA, CV-APD, and CV-DI, respectively). We computed excitation median frequency (Median_F), spectral width of the AP and ECG (SpW-AP and SpW-ECG, respectively), wavebreak incidence (WBI), and recurrence of propagation direction (RPD). We found three distinct phases of local VF dynamics: "relatively periodic" (
Endoscopic Fluorescence Mapping of the Left Atrium: a Novel Experimental Approach for High Resolution Endocardial Mapping in the Intact Heart
Despite the availability of several mapping technologies for investigating the electrophysiologic mechanisms of atrial fibrillation (AF), an experimental tool enabling high-resolution mapping of electrical impulses on the endocardial surface of the intact left atrium is lacking.
Adenoviral Expression of IKs Contributes to Wavebreak and Fibrillatory Conduction in Neonatal Rat Ventricular Cardiomyocyte Monolayers
Previous studies have shown that the gating kinetics of the slow component of the delayed rectifier K(+) current (I(Ks)) contribute to postrepolarization refractoriness in isolated cardiomyocytes. However, the impact of such kinetics on arrhythmogenesis remains unknown. We surmised that expression of I(Ks) in rat cardiomyocyte monolayers contributes to wavebreak formation and facilitates fibrillatory conduction by promoting postrepolarization refractoriness. Optical mapping was performed in 44 rat ventricular myocyte monolayers infected with an adenovirus carrying the genomic sequences of KvLQT1 and minK (molecular correlates of I(Ks)) and 41 littermate controls infected with a GFP adenovirus. Repetitive bipolar stimulation was applied at increasing frequencies, starting at 1 Hz until loss of 1:1 capture or initiation of reentry. Action potential duration (APD) was significantly shorter in I(Ks)-infected monolayers than in controls at 1 to 3 Hz (P<0.05), whereas differences at higher pacing frequencies did not reach statistical significance. Stable rotors occurred in both groups, with significantly higher rotation frequencies, lower conduction velocities, and shorter action potentials in the I(Ks) group. Wavelengths in the latter were significantly shorter than in controls at all rotation frequencies. Wavebreaks leading to fibrillatory conduction occurred in 45% of the I(Ks) reentry episodes but in none of the controls. Moreover, the density of wavebreaks increased with time as long as a stable source sustained the fibrillatory activity. These results provide the first demonstration that I(Ks)-mediated postrepolarization refractoriness can promote wavebreak formation and fibrillatory conduction during pacing and sustained reentry and may have important implications in tachyarrhythmias.
Universal Scaling Law of Electrical Turbulence in the Mammalian Heart
Many biological processes, such as metabolic rate and life span, scale with body mass (BM) according to the universal law of allometric scaling: Y = aBM(b) (Y, biological process; b, scaling exponent). We investigated whether the temporal properties of ventricular fibrillation (VF), the major cause of sudden and unexpected cardiac death, scale with BM. By using high-resolution optical mapping, numerical simulations and metaanalysis of VF data in 11 mammalian species, we demonstrate that the interbeat interval of VF scales as VF(cycle) (length) = 53 x BM(1/4), spanning more than four orders of magnitude in BM from mouse to horse.
Role of Conduction Velocity Restitution and Short-term Memory in the Development of Action Potential Duration Alternans in Isolated Rabbit Hearts
Spatially discordant alternans (SDA) has been linked to life-threatening arrhythmias. The mechanisms underlying SDA development in cardiac tissue remain unclear.
Atrial Septopulmonary Bundle of the Posterior Left Atrium Provides a Substrate for Atrial Fibrillation Initiation in a Model of Vagally Mediated Pulmonary Vein Tachycardia of the Structurally Normal Heart
The posterior left atrium (PLA) and pulmonary veins (PVs) have been shown to be critical for atrial fibrillation (AF) initiation. However, the detailed mechanisms of reentry and AF initiation by PV impulses are poorly understood. We hypothesized that PV impulses trigger reentry and AF by undergoing wavebreaks as a result of sink-to-source mismatch at specific PV-PLA transitions along the septopulmonary bundle, where there are changes in thickness and fiber direction.
High-efficiency Second-harmonic Generation of Superintense Ultrashort Laser Pulses
The effect of instantaneous cubic nonlinearity on second-harmonic generation of femtosecond laser pulses is investigated. The possibility of improving generation efficiency and shortening pulse duration is analyzed. Energy conversion efficiency of 60% was obtained in an experiment in a 1 mm thickness KDP crystal at the peak intensity of 0.6 TW/cm(2) and the duration of 60 fs.
Mechanisms of Stretch-induced Atrial Fibrillation in the Presence and the Absence of Adrenocholinergic Stimulation: Interplay Between Rotors and Focal Discharges
Both atrial stretch and combined adrenocholinergic stimulation (ACS) have been shown to favor initiation and maintenance of atrial fibrillation (AF). Their respective contributions to the electrophysiological mechanism remains, however, incompletely understood.
Feather Mites (Astigmata: Psoroptidia) Parasitising the Rock Ptarmigan Lagopus Muta (Montin) (Aves: Galliformes) in Iceland
Four new species of feather mites are described from the Icelandic rock ptarmigan Lagopus muta islandorum (Faber) in Iceland. These are Metamicrolichus islandicus n. sp., Myialges borealis n. sp. (Epidermoptidae), Strelkoviacarus holoaspis n. sp. (Analgidae) and Tetraolichus lagopi n. sp. (Pterolichidae). This is the first report on feather mites associated with the Icelandic rock ptarmigan. Brief comments on the systematics and biology of corresponding feather mite genera are given. For two species, originally described in Pterolichus Robin, 1868 (Pterolichidae), new combinations are proposed, i.e. Tetraolichus gaudi (Cerný, 1971) n. comb. and T. microdiscus (Trouessart, 1887) n. comb.
Mechanisms Underlying the Antifibrillatory Action of Hyperkalemia in Guinea Pig Hearts
Hyperkalemia increases the organization of ventricular fibrillation (VF) and may also terminate it by mechanisms that remain unclear. We previously showed that the left-to-right heterogeneity of excitation and wave fragmentation present in fibrillating guinea pig hearts is mediated by chamber-specific outward conductance differences in the inward rectifier potassium current (I(K1)). We hypothesized that hyperkalemia-mediated depolarization of the reversal potential of I(K1) (E(K1)) would reduce excitability and thereby reduce VF excitation frequencies and left-to-right heterogeneity. We induced VF in Langendroff-perfused guinea pig hearts and increased the extracellular K(+) concentration ([K(+)](o)) from control (4 mM) to 7 mM (n = 5) or 10 mM (n = 7). Optical mapping enabled spatial characterization of excitation dominant frequencies (DFs) and wavebreaks, and identification of sustained rotors (>4 cycles). During VF, hyperkalemia reduced the maximum DF of the left ventricle (LV) from 31.5 +/- 4.7 Hz (control) to 23.0 +/- 4.7 Hz (7.0 mM) or 19.5 +/- 3.6 Hz (10.0 mM; p < 0.006), the left-to-right DF gradient from 14.7 +/- 3.6 Hz (control) to 4.4 +/- 1.3 Hz (7 mM) and 3.2 +/- 1.4 Hz (10 mM), the number of DF domains, and the incidence of wavebreak in the LV and interventricular regions. During 10 mM [K(+)](o), the rotation period and core area of sustained rotors in the LV increased, and VF often terminated. Two-dimensional computer simulations mimicking experimental VF predicted that clamping E(K1) to normokalemic values during simulated hyperkalemia prevented all of the hyperkalemia-induced VF changes. During hyperkalemia, despite the shortening of the action potential duration, depolarization of E(K1) increased refractoriness, leading to a slowing of VF, which effectively superseded the influence of I(K1) conductance differences on VF organization. This reduced the left-to-right excitation gradients and heterogeneous wavebreak formation. Overall, these results provide, to our knowledge, the first direct mechanistic insight into the organization and/or termination of VF by hyperkalemia.
Skeletal Myoblast Implants Induce Minor Propagation Delays, but Do Not Promote Arrhythmias in the Normal Swine Heart
Whether skeletal myoblast (SM) implants are proarrhythmic is still controversial due to conflicting pre-clinical and clinical data. We hypothesized that if SM implants are arrhythmogenic, they will facilitate the induction of ventricular tachyarrhythmias by promoting heterogeneous propagation of activation wavefronts.
A Major Role for HERG in Determining Frequency of Reentry in Neonatal Rat Ventricular Myocyte Monolayer
the rapid delayed rectifier potassium current, I(Kr), which flows through the human ether-a-go-go-related (hERG) channel, is a major determinant of the shape and duration of the human cardiac action potential (APD). However, it is unknown whether the time dependency of I(Kr) enables it to control APD, conduction velocity (CV), and wavelength (WL) at the exceedingly high activation frequencies that are relevant to cardiac reentry and fibrillation.
Targeting Atrioventricular Differences in Ion Channel Properties for Terminating Acute Atrial Fibrillation in Pigs
The goal was to terminate atrial fibrillation (AF) by targeting atrioventricular differences in ionic properties.
Structural Heterogeneity Promotes Triggered Activity, Reflection and Arrhythmogenesis in Cardiomyocyte Monolayers
Patients with structural heart disease are predisposed to arrhythmias by incompletely understood mechanisms. We hypothesized that tissue expansions promote source-to-sink mismatch leading to early after-depolarizations (EADs) and reflection of impulses in monolayers of well-polarized neonatal rat ventricular cardiomyocytes.We traced electrical propagation optically in patterned monolayers consisting of two wide regions connected by a thin isthmus.Structural heterogeneities provided a substrate for EADs, retrograde propagation along the same pathway (reflection) and reentry initiation. Reflection always originated during the action potential (AP) plateau at the distal expansion. To determine whether increased sodium current(INa) would promote EADs, we employed adenoviral transfer of Nav1.5 (Ad-Nav1.5). Compared with uninfected and adenoviral expression of green fluorescent protein (Ad-GFP; viral control),Ad-Nav1.5 significantly increased Nav1.5 protein expression, peak and persistent INa density, A Pupstroke velocity, AP duration, conduction velocity and EAD incidence, as well as reflection incidence (29.2%, n =48 vs. uninfected, 9.4%, n =64; and Ad-GFP, 4.8%, n =21). Likewise,the persistent INa agonist veratridine (0.05–3 μM) prolonged the AP, leading to EADs and reflection. Reflection led to functional reentry distally and bigeminal and trigeminal rhythms proximally. Reflection was rare in the absence of structural heterogeneities.Computer simulations demonstrated the importance of persistent INa in triggering reflection and predicted that the gradient between the depolarizing cells at the distal expansion and the repolarizing cells within the isthmus enabled retrograde flow of depolarizing electrotonic current to trigger EADs and reflection. A combination of a substrate (structural heterogeneity) and a trigger (increased persistent INa and EADs) promotes reflection and arrhythmogenesis.
A New Feather Mite Species of the Genus Picalgoides Černý, 1974 (Astigmata: Psoroptoididae) from a Passerine Host in Costa Rica
A new feather mite species, Picalgoides giganteus n. sp. (Psoroptoididae: Pandalurinae), is described from the tawny-throated leaftosser Sclerurus mexicanus Sclater (Passeriformes: Furnariidae) in Costa Rica. Among the 10 species of Picalgoides Černý, 1974, including the new one, this is the third recorded from a passerine host; the remaining seven nominal species are associated with hosts of the order Piciformes. Brief data on the host-parasite associations of Picalgoides spp. are provided. Megninia megalixus Trouessart, 1885 from the short-tailed green magpie Cissa thalassina (Temminck) is transferred to Picalgoides as P. megalixus (Trouessart, 1885) n. comb.
Time- and Frequency-domain Analyses of Atrial Fibrillation Activation Rate: the Optical Mapping Reference
Time- and frequency-domain estimates of activation rate have been proposed to guide atrial fibrillation (AF) ablation in patients, but their electrophysiological correlates are unclear.
Left-to-right Ventricular Differences in I(KATP) Underlie Epicardial Repolarization Gradient During Global Ischemia
The ionic mechanisms of electrical heterogeneity in the ischemic ventricular epicardium remain poorly understood.
Heterogeneous Atrial Wall Thickness and Stretch Promote Scroll Waves Anchoring During Atrial Fibrillation
AIMS: Atrial dilatation and myocardial stretch are strongly associated with atrial fibrillation (AF). However, the mechanisms by which the three-dimensional (3D) atrial architecture and heterogeneous stretch contribute to AF perpetuation are incompletely understood. We compared AF dynamics during stretch-related AF (pressure: 12cmH(2)O) in normal sheep hearts (n = 5) and in persistent AF (PtAF, n = 8)-remodelled hearts subjected to prolonged atrial tachypacing. We hypothesized that, in the presence of stretch, meandering 3D atrial scroll waves (ASWs) anchor in regions of large spatial gradients in wall thickness. METHODS AND RESULTS: We implemented a high-resolution optical mapping set-up that enabled simultaneous epicardial- and endoscopy-guided endocardial recordings of the intact atria in Langendorff-perfused normal and PtAF (AF duration: 21.3 ± 11.9 days) hearts. The numbers and lifespan of long-lasting ASWs (>3 rotations) were greater in PtAF than normal (lifespan 0.9 ± 0.5 vs. 0.4 ± 0.2 s/(3 s of AF), P< 0.05). Than normal hearts, focal breakthroughs interacted with ASWs at the posterior left atrium and left atrial appendage to maintain AF. In PtAF hearts, ASW filaments seemed to span the atrial wall from endocardium to epicardium. Numerical simulations using 3D atrial geometries (Courtemanche-Ramirez-Nattel human atrial model) predicted that, similar to experiments, filaments of meandering ASWs stabilized at locations with large gradients in myocardial thickness. Moreover, simulations predicted that ionic remodelling and heterogeneous distribution of stretch-activated channel conductances contributed to filament stabilization. CONCLUSION: The heterogeneous atrial wall thickness and atrial stretch, together with ionic and anatomic remodelling caused by AF, are the main factors allowing ASW and AF maintenance.
