Numerical Model for the Determination of Erythrocyte Mechanical Properties and Wall Shear Stress in vivo From Intravital Microscopy

Abstract Interaction between neutrophils and platelets at the site of vascular damage or in ischaemic tissue may promote thrombosis and/or vascular occlusion. To study this interaction, we have developed a novel technique that allows visualization of adhesion of flowing neutrophils to immobilized, activated platelets. The total number of adherent neutrophils decreased with increasing wall shear stress in the range 0.05 to 0.4 Pa. Although a proportion of the adherent neutrophils were stationary, most were rolling with a velocity greater than 0.4 micron/s. The percentage of rolling cells increased with increasing wall shear stress, but the mean rolling cell velocity was nearly independent of shear stress. Adhesion of neutrophils was nearly abolished by treatment of the platelets with antibody to P-selectin, or by treatment of neutrophils with either neuraminidase, dextran sulfate, or EDTA. Studies with a series of antibodies to L-selectin (TQ-1, Dreg- 56, LAM1–3, and LAM1–10) suggested that this molecule was one neutrophil ligand for rolling adhesion. Thus, sialylated carbohydrate on neutrophils appears essential for P-selectin-mediated adhesion, and a proportion of this ligand may be presented by L-selectin. Treatment of the neutrophils with N-formyl-methionyl-leucyl-phenylalanine decreased the number of rolling cells, and increased the rolling velocity, possibly due to shedding of neutrophil ligand(s) and/or cell shape change. In vivo, immobilized platelets could play an important role in promoting attachment of neutrophils to vessel walls, eg, by slowing neutrophils so that integrin-mediated immobilization could occur.

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Exploring High Frequency Temporal Fluctuations in the Terminal Aneurysm of the Basilar Bifurcation

Journal of Biomechanical Engineering ◽

10.1115/1.4007279 ◽

2012 ◽

Vol 134 (9) ◽

Cited By ~ 15

Author(s):

Matthew D. Ford ◽

Ugo Piomelli

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

High Frequency ◽

Cerebral Aneurysms ◽

Patient Specific ◽

Disturbed Flow ◽

Frequency Fluctuations ◽

Wall Shear ◽

Inflow Jet

Cerebral aneurysms are a common cause of death and disability. Of all the cardiovascular diseases, aneurysms are perhaps the most strongly linked with the local fluid mechanic environment. Aside from early in vivo clinical work that hinted at the possibility of high-frequency intra-aneurysmal velocity oscillations, flow in cerebral aneurysms is most often assumed to be laminar. This work investigates, through the use of numerical simulations, the potential for disturbed flow to exist in the terminal aneurysm of the basilar bifurcation. The nature of the disturbed flow is explored using a series of four idealized basilar tip models, and the results supported by four patient specific terminal basilar tip aneurysms. All four idealized models demonstrated instability in the inflow jet through high frequency fluctuations in the velocity and the pressure at approximately 120 Hz. The instability arises through a breakdown of the inflow jet, which begins to oscillate upon entering the aneurysm. The wall shear stress undergoes similar high-frequency oscillations in both magnitude and direction. The neck and dome regions of the aneurysm present 180 deg changes in the direction of the wall shear stress, due to the formation of small recirculation zones near the shear layer of the jet (at the frequency of the inflow jet oscillation) and the oscillation of the impingement zone on the dome of the aneurysm, respectively. Similar results were observed in the patient-specific models, which showed high frequency fluctuations at approximately 112 Hz in two of the four models and oscillations in the magnitude and direction of the wall shear stress. These results demonstrate that there is potential for disturbed laminar unsteady flow in the terminal aneurysm of the basilar bifurcation. The instabilities appear similar to the first instability mode of a free round jet.

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Design and Analysis of a Shear Stress Sensor for Microcirculation Investigations (Invited Paper)

Volume 2: Symposia, Parts A, B, and C ◽

10.1115/fedsm2003-45069 ◽

2003 ◽

Author(s):

Risa Robinson ◽

Lynn Fuller ◽

Harvey Palmer ◽

Mary Frame

Keyword(s):

Blood Flow ◽

Shear Stress ◽

Wall Shear Stress ◽

Computational Technique ◽

Flow Modification ◽

Stress Sensors ◽

Shear Stress Sensors ◽

Wall Shear

Blood flow regulation in the microvascular network has been investigated by means of computational fluid dynamics, in vivo particle tracking and microchannel models. It is evident from these studies that shear stress along the wall is a key factor in the communication network that results in blood flow modification, yet current methods for shear stress determination are acknowledged to be imprecise. Micromachining technology allows for the development of implantable shear stress sensors that will enable us to monitor wall shear stress at multiple locations in arteriole bifurcations. In this study, a microchannel was employed as an in vitro model of a microvessel. Thermal shear stress sensors were used to mimic the endothelial cells that line the vessel wall. A three dimensional computational model was created to simulate the system’s thermal response to the constant temperature control circuit and related wall shear stress. The model geometry included a silicon wafer section with all the fabrication layers — silicon dioxide, poly silicon resistor, silicon nitride — and a microchannel with cross section 17 μm × 17 μm. This computational technique was used to optimize the dimensions of the system for a 0.01 Reynolds number flow at room temperature in order to reduce the amount of heat lost to the substrate and to predict and maximize the signal response. Results of the design optimization are presented and the fabrication process discussed.

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Inflammatory Response of Endothelial Cells to Wall Shear Stress in Three Dimensional Stenotic Models

ASME 2009 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2009-206669 ◽

2009 ◽

Author(s):

Leonie Rouleau ◽

Joanna Rossi ◽

Jean-Claude Tardif ◽

Rosaire Mongrain ◽

Richard L. Leask

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Wall Shear Stress ◽

Three Dimensional ◽

Realistic Model ◽

In Vitro Models ◽

Steady Flows ◽

Wall Shear

Endothelial cells (ECs) are believed to respond differentially to hemodynamic forces in the vascular tree. Once atherosclerotic plaque has formed in a vessel, the obstruction creates complex spatial gradients in wall shear stress (WSS). In vitro models have used mostly unrealistic and simplified geometries, which cannot reproduce accurately physiological conditions. The objective of this study was to expose ECs to the complex WSS pattern created by an asymmetric stenosis. Endothelial cells were grown and exposed for different times to physiological steady flows in straight dynamic controls and in idealized asymmetric stenosis models. Cell morphology was noticeably different in the regions with spatial WSS gradients, being more randomly oriented and of cobblestone shape. Inflammatory molecule expression was also altered by exposure to shear and endothelial nitric oxide synthase (eNOS) was upregulated by its presence. A regional response in terms of inflammation was observed through confocal microscopy. This work provides a more realistic model to study endothelial cell response to spatial and temporal WSS gradients that are present in vivo and is an important advancement towards a better understanding of the mechanisms involved in coronary artery disease.

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Differential Gene Expression of Endothelial Cells Under High Wall Shear Stress and Spatial Gradients

ASME 2010 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2010-19662 ◽

2010 ◽

Author(s):

Jennifer Dolan ◽

Song Liu ◽

Hui Meng ◽

John Kolega

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

Vessel Wall ◽

Cerebral Aneurysms ◽

In Vivo Studies ◽

Spatial Gradient ◽

Flow Acceleration ◽

Spatial Gradients ◽

Wall Shear

In both human and animal models, cerebral aneurysms tend to develop at the apices of bifurcations in the cerebral vasculature. Due to the focal nature of aneurysm development it has long been speculated that hemodynamics are an important factor in aneurysm susceptibility. The local hemodynamics of bifurcations are complex, being characterized by flow impingement causing a high frictional force on the vessel wall known as wall shear stress (WSS) and significant flow acceleration or deceleration, manifested as the positive or negative spatial gradient of WSS (WSSG). In vivo studies have recently identified that aneurysm initiation occurs at areas of the vessel wall that experience a combination of both high WSS and positive WSSG [1,2]

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Applying the digital image correlation method to estimate the mechanical properties of bacterial biofilms subjected to a wall shear stress

Biofouling ◽

10.1080/08927010903104984 ◽

2009 ◽

Vol 25 (8) ◽

pp. 695-703 ◽

Cited By ~ 23

Author(s):

J. D. Mathias ◽

P. Stoodley

Keyword(s):

Mechanical Properties ◽

Shear Stress ◽

Digital Image Correlation ◽

Wall Shear Stress ◽

Digital Image ◽

Correlation Method ◽

Image Correlation ◽

Bacterial Biofilms ◽

Digital Image Correlation Method ◽

Wall Shear

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Spatial comparison between wall shear stress measures and porcine arterial endothelial permeability

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00897.2003 ◽

2004 ◽

Vol 286 (5) ◽

pp. H1916-H1922 ◽

Cited By ~ 257

Author(s):

Heather A. Himburg ◽

Deborah M. Grzybowski ◽

Andrew L. Hazel ◽

Jeffrey A. LaMack ◽

Xue-Mei Li ◽

...

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

Evans Blue ◽

Fluid Dynamic ◽

Endothelial Permeability ◽

Blue Dye ◽

Evans Blue Dye ◽

Wall Shear ◽

And Function

A better understanding of how hemodynamic factors affect the integrity and function of the vascular endothelium is necessary to appreciate more fully how atherosclerosis is initiated and promoted. A novel technique is presented to assess the relation between fluid dynamic variables and the permeability of the endothelium to macromolecules. Fully anesthetized, domestic swine were intravenously injected with the albumin marker Evans blue dye, which was allowed to circulate for 90 min. After the animals were euthanized, silicone casts were made of the abdominal aorta and its iliac branches. Pulsatile flow calculations were subsequently made in computational regions derived from the casts. The distribution of the calculated time-dependent wall shear stress in the external iliac branches was directly compared on a point-by-point basis with the spatially varying in vivo uptake of Evans blue dye in the same arteries. The results indicate that in vivo endothelial permeability to albumin decreases with increasing time-average shear stress over the normal range. Additionally, endothelial permeability increases slightly with oscillatory shear index.

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