Differential Responses of Endothelial Cells to Positive and Negative Wall Shear Stress Gradients

Author(s):  
Jennifer Dolan ◽  
Sukhjinder Singh ◽  
Hui Meng ◽  
John Kolega

Cerebral aneurysms tend to develop at bifurcation apices or the outer side of curved vessels where the blood vessel wall experiences complex hemodynamics. In vivo studies have recently revealed that the initiation of cerebral aneurysms is confined to a well-defined hemodynamic microenvironment. Specifically aneurysms form where the vessel wall experiences high fluid shear stress (wall shear stress, WSS) and flow is accelerating, so that the wall is exposed to a positive spatial gradient in the fluid shear stress (wall shear stress gradient, WSSG)[1,2]. Closer examination of such in vivo studies reveals that exposure of the vessel wall to equally high WSS in the presence of decelerating flow, that is, negative WSSG, does not result in aneurysm-like remodeling.

Author(s):  
Jennifer Dolan ◽  
Song Liu ◽  
Hui Meng ◽  
John Kolega

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]


Author(s):  
Jennifer Dolan ◽  
Frasier Sim ◽  
Hui Meng ◽  
John Kolega

In both human and animal models, cerebral aneurysms tend to develop at the apices of bifurcations in the cerebral vasculature where the blood vessel wall experiences complex hemodynamics. In vivo studies have recently revealed that the initiation of cerebral aneurysms is confined to a well-defined hemodynamic microenvironment [1,2]. Metaxa et al. [2] found that early aneurysm remodeling initiates where the vessel wall experiences high wall shear stress (WSS) and flow is accelerating, thus creating a positive spatial gradient in WSS (WSSG). Closer examination of such in vivo studies reveals that exposure of the vessel wall to equally high WSS in the presence of decelerating flow, that is, negative WSSG, does not result in aneurysm-like destruction.


2012 ◽  
Vol 134 (9) ◽  
Author(s):  
Matthew D. Ford ◽  
Ugo Piomelli

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.


Author(s):  
David S. Molony ◽  
Andrew Nencka ◽  
Zhixin Li ◽  
Ming Zhao ◽  
Don P. Giddens

Hemodynamics have been linked to the genesis and progress of vascular disease in humans and animals1. Disturbed flow patterns such as stagnant flow or flow reversal lead to low or oscillating wall shear stress (WSS). Several in-vivo studies have correlated these types of WSS with disease formation1, 2. The desire to find correlations between markers of vascular disease and mechanical stimuli and because of their easier availability has led to an increasing number of animal model studies. The mouse, in particular, is a commonly used animal for investigating vascular disease formation and progression. Suo et al., were one of the first to relate findings on the molecular level with WSS1. They found increased VCAM and ICAM expression in areas of low WSS. More recently Hoi et al.2, have shown a correlation between atherosclerotic plaque development and hemodynamic parameters such as low time averaged wall shear stress (TAWSS) and Oscillatory Shear Index (OSI).


2006 ◽  
Author(s):  
Yong Hyun Kim ◽  
Joon Sand Lee ◽  
Xin Wu

Vascular techniques have been used for curing the aneurysm, but the reason for the occurrence of aneurysms can not be known using these techniques. These techniques are usually used for preventing a significant situation such as rupture of an aneurysm. In our study, blood flow effects with or without vascular techniques inside an aneurysm were analyzed with computational fluid dynamics (CFD). Important hemodynamic quantities like wall shear stress and pressure in vessel are difficult to measure in-vivo. Blood flow is assumed to be Newtonian fluid. But it actually consists of platelets, so it is also considered a non-Newtonian fluid in this study. Results of the numerical model were used to compare and analyze fluid characteristics with experimental data. Using the flow characteristics (wall shear stress (WSS), wall shear stress gradient (WSSG)), the rupture area was identified to be located in the distal area. However, the rupture area, in vivo studies, was observed to be present at a different location. During pulsatile flow, vibration induced by flow is implicated by weakening of the artery wall and affects more than shear stress. After adapting the fluid-induced vibration, the rupture area in aneurysm is found to be located in the same area as the in-vivo result. Since smaller inflow and low WSS provide the effect of the distal neck, the vibration provides more effects in dome area. In this study it has been found that the effect of shear stress on the rupture of aneurysm is less than the effect of vibration. In the case of non-Newtonian fluid, vibration induced by flow also has more effects than WSS and WSSG. The simulation results gave detailed information about hemodynamics under physiological pulsatile inlet condition.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Jon Koch ◽  
John Borg ◽  
Abby Mattson ◽  
Kris Olsen ◽  
James Bahcall

Objective. This in vitro study compared the flow pattern and shear stress of an irrigant induced by ultrasonic and polymer rotary finishing file activation in an acrylic root canal model. Flow visualization analysis was performed using an acrylic canal filled with a mixture of distilled water and rheoscopic fluid. The ultrasonic and polymer rotary finishing file were separately tested in the canal and activated in a static position and in a cyclical axial motion (up and down). Particle movement in the fluid was captured using a high-speed digital camera and DaVis 7.1 software. The fluid shear stress analysis was performed using hot film anemometry. A hot-wire was placed in an acrylic root canal and the canal was filled with distilled water. The ultrasonic and polymer rotary finishing files were separately tested in a static position and in a cyclical axial motion. Positive needle irrigation was also tested separately for fluid shear stress. The induced wall shear stress was measured using LabVIEW 8.0 software.


1997 ◽  
Vol 136 (3) ◽  
pp. 717-727 ◽  
Author(s):  
Michael B. Lawrence ◽  
Geoffrey S. Kansas ◽  
Eric J. Kunkel ◽  
Klaus Ley

Leukocyte adhesion through L-selectin to peripheral node addressin (PNAd, also known as MECA-79 antigen), an L-selectin ligand expressed on high endothelial venules, has been shown to require a minimum level of fluid shear stress to sustain rolling interactions (Finger, E.B., K.D. Puri, R. Alon, M.B. Lawrence, V.H. von Andrian, and T.A. Springer. 1996. Nature (Lond.). 379:266–269). Here, we show that fluid shear above a threshold of 0.5 dyn/cm2 wall shear stress significantly enhances HL-60 myelocyte rolling on P- and E-selectin at site densities of 200/μm2 and below. In addition, gravitational force is sufficient to detach HL60 cells from P- and E-selectin substrates in the absence, but not in the presence, of flow. It appears that fluid shear–induced torque is critical for the maintenance of leukocyte rolling. K562 cells transfected with P-selectin glycoprotein ligand-1, a ligand for P-selectin, showed a similar reduction in rolling on P-selectin as the wall shear stress was lowered below 0.5 dyn/cm2. Similarly, 300.19 cells transfected with L-selectin failed to roll on PNAd below this level of wall shear stress, indicating that the requirement for minimum levels of shear force is not cell type specific. Rolling of leukocytes mediated by the selectins could be reinitiated within seconds by increasing the level of wall shear stress, suggesting that fluid shear did not modulate receptor avidity. Intravital microscopy of cremaster muscle venules indicated that the leukocyte rolling flux fraction was reduced at blood centerline velocities less than 1 mm/s in a model in which rolling is mediated by L- and P-selectin. Similar observations were made in L-selectin–deficient mice in which leukocyte rolling is entirely P-selectin dependent. Leukocyte adhesion through all three selectins appears to be significantly enhanced by a threshold level of fluid shear stress.


Author(s):  
Juan R. Cebral ◽  
Christopher M. Putman

Cerebral aneurysms are widely believed to form and grow as a result of the interactions of hemodynamics and wall mechano-biology. Researchers have used a variety of tools to study these complex multi-factorial mechanisms including animal, in vitro, and computational models. The goal of these experiments has been to approximate the in vivo environment so that theories about the natural history of brain aneurysms can be developed and tested in realistic systems. Studying the link between hemodynamics and clinical observations of aneurysm progression is necessary to reach an understanding of the relative importance of the different mechanisms involved in these processes [1]. The objective of our research is to investigate the possible relationship between wall shear stress (WSS) — which is known to regulate mechano-biological processes at the arterial wall — produced by different blood flow patterns and the evolution and rupture of cerebral aneurysms.


2020 ◽  
Vol 17 (168) ◽  
pp. 20190884
Author(s):  
S. Lee ◽  
N. Kwok ◽  
J. Holsapple ◽  
T. Heldt ◽  
L. Bourouiba

The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using in vitro microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zones that can favour the growth and adhesion of astrocytes, thus promoting obstruction. Using high-precision direct flow visualization and CFD simulations, we discover that the catheter flow can be formulated as a network of Poiseuille flows. Based on this observation, we leverage a Poiseuille network model to optimize ventricular catheter design such that the distribution of wall shear stress is above a critical threshold to minimize astrocyte adhesion and growth. Using this approach, we also suggest a novel design principle that not only optimizes the wall shear stress distribution but also eliminates a stagnation zone with low wall shear stress, which is common to current ventricular catheters.


2019 ◽  
Vol 131 ◽  
pp. e599-e605 ◽  
Author(s):  
Denise Brunozzi ◽  
Peter Theiss ◽  
Amanda Andrews ◽  
Sepideh Amin-Hanjani ◽  
Fady T. Charbel ◽  
...  

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