Cardiac sodium channelopathies

Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (INa) during phase 0 of the cardiac action potential. The importance of INa for normal cardiac electrical activity is reflected by the high incidence of arrhythmias in cardiac sodium channelopathies, i.e., arrhythmogenic diseases in patients with mutations in SCN5A, the gene responsible for the pore-forming ion-conducting α-subunit, or in genes that encode the ancillary β-subunits or regulatory proteins of the cardiac sodium channel. While clinical and genetic studies have laid the foundation for our understanding of cardiac sodium channelopathies by establishing links between arrhythmogenic diseases and mutations in genes that encode various subunits of the cardiac sodium channel, biophysical studies (particularly in heterologous expression systems and transgenic mouse models) have provided insights into the mechanisms by which INa dysfunction causes disease in such channelopathies. It is now recognized that mutations that increase INa delay cardiac repolarization, prolong action potential duration, and cause long QT syndrome, while mutations that reduce INa decrease cardiac excitability, reduce electrical conduction velocity, and induce Brugada syndrome, progressive cardiac conduction disease, sick sinus syndrome, or combinations thereof. Recently, mutation-induced INa dysfunction was also linked to dilated cardiomyopathy, atrial fibrillation, and sudden infant death syndrome. This review describes the structure and function of the cardiac sodium channel and its various subunits, summarizes major cardiac sodium channelopathies and the current knowledge concerning their genetic background and underlying molecular mechanisms, and discusses recent advances in the discovery of mutation-specific therapies in the management of these channelopathies

High-order computation of burning propellant surface and simulation of fluid flow in solid rocket chamber

International audienceIn this paper, we present a numerical approach for predicting fluid flows in solid rocket motor (SRM) chambers. We use a novel high-order technique to track the burning grain surface. Spectral convergence toward the exact burning surface is achieved thanks to Fourier differentiation. In addition, we make use of a body-fitted mesh deforming with the burning surface and present a method to avoid manual remeshing. We describe several methods to deform the volume mesh and to keep good mesh element quality during the computation. We then couple the surface and volume approaches. The resulting coupled method is able to handle the formation of geometric singularities on the burning surface while keeping constant surface and volume mesh topology. This geometrical approach is integrated into a complex code for compressible, multi-species, turbulent flow simulations. Applications to the simulation of the internal flow in realistic solid rocket motors with complex grain geometry are then presented

Simulations of solid propellant rocket motors instability including propellant combustion response

Communication to : 6th International congress on sound and vibration, Lyngby (Denmark), July 05-08, 1999SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : 22419, issue : a.1999 n.133 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Parietal vortex shedding as a cause of instability for long solid propellant motors : numerical simulations and comparisons with firing tests

Communication to : 34th AIAA Aerospace sciences meeting and exhibit, Reno, NV (USA), january 15-18, 1996SIGLEAvailable at INIST (FR), Document Supply Service, under shelf-number : 22419, issue : a.1996 n.21 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Two-dimensional numerical simulation of the stability of a solid propellant rocket motor

Tire de : AIAA 29th Aerospace science meeting, Reno (NE, USA), january 7-10, 1991SIGLEAvailable at INIST (FR), Document Supply Service, under shelf-number : 22419, issue : a.1991 n.2 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc