Computational probabilistic quantification of pro-arrhythmic risk from scar and left-to-right heterogeneity in the human ventricles

Both scar and left-to-right ventricular (LV/RV) differences in repolarization properties have been implicated as risk factors for lethal arrhythmias. As a possible mechanism for the initiation of re-entry, a recent study has indicated that LV/RV heterogeneities in action potential duration (APD) adaptation can cause a transient increase in APD dispersion following rate acceleration, promoting unidirectional block of conduction at the LV/RV junction. In the presence of an ischemic region and ectopic stimulation, a pathological dispersion in repolarization has been suggested to increase the risk of electrical re-entry. However, the exact location and timing of the ectopic activation play a crucial role in initiation of re-entry, and certain combinations may lead to re-entry even under normal LV/RV dispersion in repolarization. This suggests that the phenomenon needs to be investigated in a quantitative way. In this study we employ a computationally efficient, phenomenological model in order to investigate the proarrhythmic properties of a range of combinations of position and timing of an ectopic activation. This allows us to probabilistically study how increasing interventricular dispersion of repolarization increases arrhythmic risk. Results indicate that a larger LV/RV dispersion in repolarization allows ectopic beats to initiate re-entry during a significantly larger time window and from a greater number of locations compared to the case of smaller LV/RV dispersion

Na/K pump regulation of cardiac repolarization: Insights from a systems biology approach

The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the Systems Biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most\ud important ionic mechanisms in regulating key properties of cardiac repolarization and its rate-dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies

What can Simbol-X do for gamma-ray binaries?

Gamma-ray binaries have been uncovered as a new class of Galactic objects in the very high energy sky (> 100 GeV). The three systems known today have hard X-ray spectra (photon index ~ 1.5), extended radio emission and a high luminosity in gamma-rays. Recent monitoring campaigns of LSI +61 303 in X-rays have confirmed variability in these systems and revealed a spectral hardening with increasing flux. In a generic one-zone leptonic model, the cooling of relativistic electrons accounts for the main spectral and temporal features observed at high energy. Persistent hard X-ray emission is expected to extend well beyond 10 keV. We explain how Simbol-X will constrain the existing models in connection with Fermi Space Telescope measurements. Because of its unprecedented sensitivity in hard X-rays, Simbol-X will also play a role in the discovery of new gamma-ray binaries, giving new insights into the evolution of compact binaries.Comment: 4 pages, 1 figure, Proceedings of the 2nd International Simbol-X symposium held in Paris, 2-5 December 200

Low polarized emission from the core of coronal mass ejections

In white-light coronagraph images, cool prominence material is sometimes observed as bright patches in the core of coronal mass ejections (CMEs). If, as generally assumed, this emission is caused by Thomson-scattered light from the solar surface, it should be strongly polarised tangentially to the solar limb. However, the observations of a CME made with the SECCHI/STEREO coronagraphs on 31 August 2007 show that the emission from these bright core patches is exceptionally low polarised. We used the polarisation ratio method of Moran and Davila (2004) to localise the barycentre of the CME cloud. By analysing the data from both STEREO spacecraft we could resolve the plane-of-the-sky ambiguity this method usually suffers from. Stereoscopic triangulation was used to independently localise the low-polarisation patch relative to the cloud. We demonstrated for the first time that the bright core material is located close to the centre of the CME cloud. We show that the major part of the CME core emission, more than 85% in our case, is H$\alpha$ radiation and only a small fraction is Thomson-scattered light. Recent calculations also imply that the plasma density in the patch is 8 10$^8$ cm$^{-3}$ or more compared to 2.6 10$^6$ cm$^{-3}$ for the Thomson-scattering CME environment surrounding the core material.Comment: 5 pages, 3 figure

Muon diffusion and electronic magnetism in Y2_2Ti2_2O7_7

We report a $\mu$SR study in a Y$_2$Ti$_2$O$_7$ single crystal. We observe slow local field fluctuations at low temperature which become faster as the temperature is increased. Our analysis suggests that muon diffusion is present in this system and becomes small below 40 K and therefore incoherent. A surprisingly strong electronic magnetic signal is observed with features typical for muons thermally diffusing towards magnetic traps below $\approx 100$ K and released from them above this temperature. We attribute the traps to Ti$^{3+}$ defects in the diluted limit. Our observations are highly relevant to the persistent spin dynamics debate on $R_2$Ti$_2$O$_7$ pyrochlores and their crystal quality

Fractional diffusion models of cardiac electrical propagation: role of structural heterogeneity in dispersion of repolarization

Structural heterogeneity constitutes one of the main substrates influencing impulse propagation in living tissues. In cardiac muscle, improved understanding on its role is key to advancing our interpretation of cell-to-cell coupling, and how tissue structure modulates electrical propagation and arrhythmogenesis in the intact and diseased heart. We propose fractional diffusion models as a novel mathematical description of structurally heterogeneous excitable media, as a mean of representing the modulation of the total electric field by the secondary electrical sources associated with tissue inhomogeneities. Our results, validated against in-vivo human recordings and experimental data of different animal species, indicate that structural heterogeneity underlies many relevant characteristics of cardiac propagation, including the shortening of action potential duration along the activation pathway, and the progressive modulation by premature beats of spatial patterns of dispersion of repolarization. The proposed approach may also have important implications in other research fields involving excitable complex media

Moving embedded lattice solitons

It was recently proved that isolated unstable "embedded lattice solitons" (ELS) may exist in discrete systems. The discovery of these ELS gives rise to relevant questions such as the following: are there continuous families of ELS?, can ELS be stable?, is it possible for ELS to move along the lattice?, how do ELS interact?. The present work addresses these questions by showing that a novel differential-difference equation (a discrete version of a complex mKdV equation) has a two-parameter continuous family of exact ELS. The numerical tests reveal that these solitons are stable and robust enough to withstand collisions. The model may apply to the description of a Bose-Einstein condensate with dipole-dipole interactions between the atoms, trapped in a deep optical-lattice potential.Comment: 13 pages, 11 figure