Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fraction of nonconducting cells

Cardiac fibrosis occurs in many forms of heart disease and is considered to be one of the main arrhythmogenic factors. Regions with a high density of fibroblasts are likely to cause blocks of wave propagation that give rise to dangerous cardiac arrhythmias. Therefore, studies of the wave propagation through these regions are very important, yet the precise mechanisms leading to arrhythmia formation in fibrotic cardiac tissue remain poorly understood. Particularly, it is not clear how wave propagation is organized at the cellular level, as experiments show that the regions with a high percentage of fibroblasts (65-75%) are still conducting electrical signals, whereas geometric analysis of randomly distributed conducting and non-conducting cells predicts connectivity loss at 40% at the most (percolation threshold). To address this question, we used a joint in vitro-in silico approach, which combined experiments in neonatal rat cardiac monolayers with morphological and electrophysiological computer simulations. We have shown that the main reason for sustainable wave propagation in highly fibrotic samples is the formation of a branching network of cardiomyocytes. We have successfully reproduced the morphology of conductive pathways in computer modelling, assuming that cardiomyocytes align their cytoskeletons to fuse into cardiac syncytium. The electrophysiological properties of the monolayers, such as conduction velocity, conduction blocks and wave fractionation, were reproduced as well. In a virtual cardiac tissue, we have also examined the wave propagation at the subcellular level, detected wavebreaks formation and its relation to the structure of fibrosis and, thus, analysed the processes leading to the onset of arrhythmias. © 2019 Kudryashova et al

Control of scroll wave turbulence using resonant perturbations

Turbulence of scroll waves is a sort of spatio-temporal chaos that exists in three-dimensional excitable media. Cardiac tissue and the Belousov-Zhabotinsky reaction are examples of such media. In cardiac tissue, chaotic behaviour is believed to underlie fibrillation which, without intervention, precedes cardiac death. In this study we investigate suppression of the turbulence using stimulation of two different types, "modulation of excitability" and "extra transmembrane current". With cardiac defibrillation in mind, we used a single pulse as well as repetitive extra current with both constant and feedback controlled frequency. We show that turbulence can be terminated using either a resonant modulation of excitability or a resonant extra current. The turbulence is terminated with much higher probability using a resonant frequency perturbation than a non-resonant one. Suppression of the turbulence using a resonant frequency is up to fifty times faster than using a non-resonant frequency, in both the modulation of excitability and the extra current modes. We also demonstrate that resonant perturbation requires strength one order of magnitude lower than that of a single pulse, which is currently used in clinical practice to terminate cardiac fibrillation. Our results provide a robust method of controlling complex chaotic spatio-temporal processes. Resonant drift of spiral waves has been studied extensively in two dimensions, however, these results show for the first time that it also works in three dimensions, despite the complex nature of the scroll wave turbulence.Comment: 13 pages, 12 figures, submitted to Phys Rev E 2008/06/13. Last version: 2008/09/18, after revie

Intrinsic Localized Modes Observed in the High Temperature Vibrational Spectrum of NaI

Inelastic neutron measurements of the high-temperature lattice excitations in NaI show that in thermal equilibrium at 555 K an intrinsic mode, localized in three dimensions, occurs at a single frequency near the center of the spectral phonon gap, polarized along [111]. At higher temperatures the intrinsic localized mode gains intensity. Higher energy inelastic neutron and x-ray scattering measurements on a room-temperature NaI crystal indicate that the creation energy of the ground state of the intrinsic localized mode is 299 meV.Comment: 17 pages, 5 figures Revised version; final versio

Nuclear spin driven quantum relaxation in LiY_0.998Ho_0.002F_4

Staircase hysteresis loops of the magnetization of a LiY_0.998Ho_0.002F_4 single crystal are observed at subkelvin temperatures and low field sweep rates. This behavior results from quantum dynamics at avoided level crossings of the energy spectrum of single Ho^{3+} ions in the presence of hyperfine interactions. Enhanced quantum relaxation in constant transverse fields allows the study of the relative magnitude of tunnel splittings. At faster sweep rates, non-equilibrated spin-phonon and spin-spin transitions, mediated by weak dipolar interactions, lead to magnetization oscillations and additional steps.Comment: 5 pages, 5 eps figures, using RevTe

Generation and escape of local waves from the boundary of uncoupled cardiac tissue

We aim to understand the formation of abnormal waves of activity from myocardial regions with diminished cell-to-cell coupling. In route to this goal, we studied the behavior of a heterogeneous myocyte network in which a sharp coupling gradient was placed under conditions of increasing network automaticity. Experiments were conducted in monolayers of neonatal rat cardiomyocytes using heptanol and isoproterenol as means of altering cell-to-cell coupling and automaticity respectively. Experimental findings were explained and expanded using a modified Beeler-Reuter numerical model. The data suggests that the combination of a heterogeneous substrate, a gradient of coupling and an increase in oscillatory activity of individual cells creates a rich set of behaviors associated with self-generated spiral waves and ectopic sources. Spiral waves feature a flattened shape and a pin-unpin drift type of tip motion. These intercellular waves are action-potential based and can be visualized with either voltage or calcium transient measurements. A source/load mismatch on the interface between the boundary and well-coupled layers can lock wavefronts emanating from both ectopic sources and rotating waves within the inner layers of the coupling gradient. A numerical approach allowed us to explore how: i) the spatial distribution of cells, ii) the amplitude and dispersion of cell automaticity, iii) and the speed at which the coupling gradient moves in space, affects wave behavior, including its escape into well-coupled tissue.Comment: 28 pages, 10 figures, submitted to Biophysical Journa

Theory of spiral wave dynamics in weakly excitable media: asymptotic reduction to a kinematic model and applications

In a weakly excitable medium, characterized by a large threshold stimulus, the free end of an isolated broken plane wave (wave tip) can either rotate (steadily or unsteadily) around a large excitable core, thereby producing a spiral pattern, or retract causing the wave to vanish at boundaries. An asymptotic analysis of spiral motion and retraction is carried out in this weakly excitable large core regime starting from the free-boundary limit of the reaction-diffusion models, valid when the excited region is delimited by a thin interface. The wave description is shown to naturally split between the tip region and a far region that are smoothly matched on an intermediate scale. This separation allows us to rigorously derive an equation of motion for the wave tip, with the large scale motion of the spiral wavefront slaved to the tip. This kinematic description provides both a physical picture and exact predictions for a wide range of wave behavior, including: (i) steady rotation (frequency and core radius), (ii) exact treatment of the meandering instability in the free-boundary limit with the prediction that the frequency of unstable motion is half the primary steady frequency (iii) drift under external actions (external field with application to axisymmetric scroll ring motion in three-dimensions, and spatial or/and time-dependent variation of excitability), and (iv) the dynamics of multi-armed spiral waves with the new prediction that steadily rotating waves with two or more arms are linearly unstable. Numerical simulations of FitzHug-Nagumo kinetics are used to test several aspects of our results. In addition, we discuss the semi-quantitative extension of this theory to finite cores and pinpoint mathematical subtleties related to the thin interface limit of singly diffusive reaction-diffusion models

Sub-millimeter to centimeter excess emission from the Magellanic Clouds. I. Global spectral energy distribution

In order to reconstruct the global SEDs of the Magellanic Clouds over eight decades in spectral range, we combined literature flux densities representing the entire LMC and SMC respectively, and complemented these with maps extracted from the WMAP and COBE databases covering the missing the 23--90 GHz (13--3.2 mm) and the poorly sampled 1.25--250 THz (240--1.25 micron). We have discovered a pronounced excess of emission from both Magellanic Clouds, but especially the SMC, at millimeter and sub-millimeter wavelengths. We also determined accurate thermal radio fluxes and very low global extinctions for both LMC and SMC. Possible explanations are briefly considered but as long as the nature of the excess emission is unknown, the total dust masses and gas-to-dust ratios of the Magellanic Clouds cannot reliably be determined.Comment: Accepted for publication by A&

The global dust SED: Tracing the nature and evolution of dust with DustEM

The Planck and Herschel missions are currently measuring the farIR-mm emission of dust, which combined with existing IR data, will for the first time provide the full SED of the galactic ISM dust emission with an unprecedented sensitivity and angular resolution. It will allow a systematic study of the dust evolution processes that affect the SED. Here we present a versatile numerical tool, DustEM, that predicts the emission and extinction of dust given their size distribution and their optical and thermal properties. In order to model dust evolution, DustEM has been designed to deal with a variety of grain types, structures and size distributions and to be able to easily include new dust physics. We use DustEM to model the dust SED and extinction in the diffuse interstellar medium at high-galactic latitude (DHGL), a natural reference SED. We present a coherent set of observations for the DHGL SED. The dust components in our DHGL model are (i) PAHs, (ii) amorphous carbon and (iii) amorphous silicates. We use amorphous carbon dust, rather than graphite, because it better explains the observed high abundances of gas-phase carbon in shocked regions of the interstellar medium. Using the DustEM model, we illustrate how, in the optically thin limit, the IRAS/Planck HFI (and likewise Spitzer/Herschel for smaller spatial scales) photometric band ratios of the dust SED can disentangle the influence of the exciting radiation field intensity and constrain the abundance of small grains relative to the larger grains. We also discuss the contributions of the different grain populations to the IRAS, Planck and Herschel channels. Such information is required to enable a study of the evolution of dust as well as to systematically extract the dust thermal emission from CMB data and to analyze the emission in the Planck polarized channels. The DustEM code described in this paper is publically available.Comment: accepted for publication in A&

Inverse temperature dependence of the dust submillimeter spectral index

We present a compilation of PRONAOS-based results concerning the temperature dependence of the dust submillimeter spectral index, including data from Galactic cirrus, star-forming regions, dust associated to a young stellar object, and a spiral galaxy. We observe large variations of the spectral index (from 0.8 to 2.4) in a wide range of temperatures (11 to 80 K). These spectral index variations follow a hyperbolic-shaped function of the temperature, high spectral indices (1.6-2.4) being observed in cold regions (11-20 K) while low indices (0.8-1.6) are observed in warm regions (35-80 K). Three distinct effects may play a role in this temperature dependence: one is that the grain sizes change in dense environments, another is that the chemical composition of the grains is not the same in different environments, a third one is that there is an intrinsic dependence of the dust spectral index on the temperature due to quantum processes. This last effect is backed up by laboratory measurements and could be the dominant one.Comment: 5 pages, 3 figures, Letter accepted April 2003 in A&