Kamen N. Beronov

Carotid Plaque Vulnerability A Positive Feedback Between Hemodynamic and Biochemical Mechanisms

Background and Purpose— Rupture of atherosclerotic plaques is one of the main causes of ischemic strokes. The aim of this study was to investigate carotid plaque vulnerability markers in relation to blood flow direction and the mechanisms leading to plaque rupture at the upstream side of carotid stenoses. Methods— Frequency and location of rupture, endothelial erosion, neovascularization, and hemorrhage were determined in longitudinal sections of 80 human carotid specimens. Plaques were immunohistochemically analyzed for markers of vulnerability. Plaque geometry was measured to reconstruct shape profiles of ruptured versus stable plaques and to perform computational fluid dynamics analyses. Results— In 86% of ruptured plaques, rupture was observed upstream. In this region, neovascularization and hemorrhage were increased, along with increased immunoreactivity of vascular endothelial and connective tissue growth factor, whereas endothelial erosion was more frequent downstream. Proteolytic enzymes, mast cell chymase and cathepsin L, and the proapoptotic protein Bax showed significantly higher expression upstream as compared with the downstream shoulder of atherosclerotic lesions. Comparison of geometric profiles for ruptured and stable plaques showed increased longitudinal asymmetry of fibrous cap and lipid core thickness in ruptured plaques. The specific geometry of plaques ruptured upstream induced increased levels of shear stress and increased pressure drop between the upstream and the downstream plaque shoulders. Conclusions— Vulnerability of the upstream plaque region is associated with enhanced neovascularization, hemorrhage, and cap thinning induced by proteolytic and proapoptotic mechanisms. These processes are reflected in structural plaque characteristics, analyses of which could improve the efficacy of vascular diagnostics and prevention.

Shear stress preconditioning modulates endothelial susceptibility to circulating TNF-α and monocytic cell recruitment in a simplified model of arterial bifurcations

OBJECTIVE Atherosclerotic plaque formation results from a combination of local shear stress patterns and inflammatory processes. This study investigated the endothelial response to shear stress in combination with the inflammatory cytokine TNF-alpha in a simplified model of arterial bifurcation. METHODS Human umbilical vein endothelial cells (ECs) were exposed to laminar or non-uniform shear stress in bifurcating flow-through slides, followed by stimulation with TNF-alpha. To study cell adhesion, ECs were perfused with medium containing THP-1 monocytic cells. Endothelial protein expression was determined by immunofluorescence. RESULTS Adhesion of monocytic cells to unstimulated ECs was nearly undetectable under laminar shear stress and was slightly increased under non-uniform shear stress. Exposure of ECs to non-uniform shear stress in combination with TNF-alpha induced a 12-fold increase in monocytic cell recruitment and a significant induction of endothelial E-selectin and VCAM-1 expression. Both these effects were prevented in ECs exposed to laminar shear stress. The significant differences in TNF-alpha-induced monocytic cell recruitment and adhesion molecule expression between laminar and non-uniform shear stress regions were abolished in the absence of shear stress preconditioning. Simvastatin (1 micromol/L) suppressed the non-uniform shear stress- and TNF-alpha-induced increase in monocytic cell adhesion by about 30% via inhibition of VCAM-1 expression. Resveratrol, the active component of red wine, inhibited the expression of both VCAM-1 and E-selectin, and reduced monocytic cell recruitment by 50% at 20 micromol/L. CONCLUSIONS Non-uniform shear stress induces endothelial susceptibility to circulating TNF-alpha and adhesion of monocytic cells. Interference with this process may inhibit inflammatory response in atherosclerosis-prone regions.

Homogeneity of turbulence generated by static-grid structures

Homogeneity of turbulence generated by static grids is investigated with the help of hot-wire measurements in a wind-tunnel and direct numerical simulations based on the Lattice Bolztmann method. It is shown experimentally that Reynolds stresses and their anisotropy do not become homogeneous downstream of the grid, independent of the mesh Reynolds number for a grid porosity of 64 %, which is higher than the lowest porosities suggested in the literature to realize homogeneous turbulence downstream of the grid. In order to validate the experimental observations and elucidate possible reasons for the inhomogeneity, direct numerical simulations have been performed over a wide range of grid porosity at a constant mesh Reynolds number. It is found from the simulations that the turbulence wake behind the symmetric grids is only homogeneous in its mean velocity but is inhomogeneous when turbulence quantities are considered, whereas the mean velocity field becomes inhomogeneous in the wake of a slightly non-uniform grid. The simulations are further analysed by evaluating the terms in the transport equation of the kinetic energy of turbulence to provide an explanation for the persistence of the inhomogeneity of Reynolds stresses far downstream of the grid. It is shown that the early homogenization of the mean velocity field hinders the homogenization of the turbulence field.

Direct Simulation with the Lattice Boltzmann Code BEST of Developed Turbulence in Channel Flows

In spite of the dramatic increase of the performance of recent supercomputers the direct numerical simulation (DNS) of turbulent flows is still an expensive venture in view of the high memory and CPU time requirements. Today, the DNS is limited to very low Reynolds number and simple flow geometries which are far away from technical relevance. Therefore, there is an increasing demand in the development of numerical schemes to simulate fluid flows resolving the turbulent scales in order to exploit existing and future supercomputers more efficiently. In that context, the lattice Boltzmann method have challenged the traditionally used DNS method based on FV or pseu-dospektral . The potential of these LBM have been clearly shown in various publications [4]. The goal of the present paper is to specify the advantages of the LBM to DNS more quantitatively and to make use of the LBM to investigate new phenomena related to wall bounded turbulence.

On the Difficulties in Resolving the Viscous Sublayer in Wall-Bounded Turbulence

Comparison of one-point statistics of turbulent velocities in the near-wall region y + < 10 from DNS of turbulent plane channel flows with corresponding data from experiments on wall-bounded turbulence show that DNS data are plagued by an overprediction of turbulent intensity and intermittency. This is the result of a spurious non-analyticity of logarithmic type, which arises from the violation by numerical approximations of a fine cancellation of high-order terms in y + in the equation for the wall-normal velocity component v. The arising non-analytic additive error propagates into all hydrodynamic fields, but affects most strongly v which vanishes at the wall faster than the other velocity components. Its normalized moments like the flatness factor F v are dominated by the error, with dramatic effects. For example, overprediction of F v is larger in DNS with higher resolution. This paradoxical observation is explained by a simple model accounting for the high intermittency and for the log-errors of v near the wall.

Statistics and Intermittency of Developed Channel Flows: a Grand Challenge in Turbulence Modeling and Simulation

Studying and modeling turbulence in wall-bounded flows is important in many engineering fields, such as transportation, power generation or chemical engineering. Despite its long history, it remains disputable even in its basic aspects and even if only simple flow types are considered. Focusing on the best studied flow type, which has also direct applications, we argue that not only its theoretical description, but also its experimental measurement and numerical simulation are objectively limited in range and precision, and that it is necessary to bridge gaps between parameter ranges that are covered by different approaches. Currently, this can only be achieved by expanding the range of numerical simulations, a grand challenge even for the most powerful computational resources just becoming available. The required setup and desired output of such simulations are specified, along with estimates of the computing effort on the NEC SX-8 supercomputer at HLRS.

Numerische Simulation pulsierender Strömungen in Blutgefäßen des Gehirns mit Aneurysmen mittels Lattice-Boltzmann-Verfahren

A major prerequisite for successful planning and control of the medical treatment of blood vessels with stenoses or aneurysms is the detailed knowledge of the individual situation in the damaged vessels. Modern tomography methods provide good spatial resolution, so that vessel walls as well as prostheses can be easily and rapidly identified. However, the mechanical loads of the walls remain largely unknown. In the past few years, tomography data have been used for spatial and temporal simulations of the blood flow in such vessels and to predict the mechanical loads of the vessel walls. The methodologies used so far, however, involve elaborate grid generation and simulation steps, most often relying on commercial software suited for engineering projects. These require specific knowledge and experience in mechanics and numerical simulation, and are therefore inappropriate for clinical applications. It is now shown, by example of an intracranial aneurysm, that employing a Lattice Boltzmann method for the flow simulation allows to avoid all mentioned drawbacks and to simulate blood flows in a fast and simple way that is also appropriate for clinical use. The practical relevance of such simulations will be enhanced by a better understanding of the correlations between pathology and specific mechanical loads. The paper discusses also some aspects of fluid mechanics that are relevant for the study of aneurysms.A major prerequisite for successful planning and control of the medical treatment of blood vessels with stenoses or aneurysms is the detailed knowledge of the individual situation in the damaged vessels. Modern tomography methods provide good spatial resolution, so that vessel walls as well as prostheses can be easily and rapidly identified. However, the mechanical loads of the walls remain largely unknown. In the past few years, tomography data have been used for spatial and temporal simulations of the blood flow in such vessels and to predict the mechanical loads of the vessel walls. The methodologies used so far, however, involve elaborate grid generation and simulation steps, most often relying on commercial software suited for engineering projects. These require specific knowledge and experience in mechanics and numerical simulation, and are therefore inappropriate for clinical applications. It is now shown, by example of an intracranial aneurysm, that employing a Lattice Boltzmann method for the flow simulation allows to avoid all mentioned drawbacks and to simulate blood flows in a fast and simple way that is also appropriate for clinical use. The practical relevance of such simulations will be enhanced by a better understanding of the correlations between pathology and specific mechanical loads. The paper discusses also some aspects of fluid mechanics that are relevant for the study of aneurysms.