Low Mean Wall Shear Stress Research Articles

Endothelial cells do not align with the mean wall shear stress vector.

The alignment of arterial endothelial cells (ECs) with the mean wall shear stress (WSS) vector is the prototypical example of their responsiveness to flow. However, evidence for this behaviour rests on experiments where many WSS metrics had the same orientation or where they were incompletely characterized. In the present study, we tested the phenomenon more rigorously. Aortic ECs were cultured in cylindrical wells on the platform of an orbital shaker. In this system, orientation would differ depending on the WSS metric to which the cells aligned. Variation in flow features and hence in possible orientations was further enhanced by altering the viscosity of the medium. Orientation of endothelial nuclei was compared with WSS characteristics obtained by computational fluid dynamics. At low mean WSS magnitudes, ECs aligned with the modal WSS vector, while at high mean WSS magnitudes they aligned so as to minimize the shear acting across their long axis (transverse WSS). Their failure to align with the mean WSS vector implies that other aspects of endothelial behaviour attributed to this metric require re-examination. The evolution of a mechanism for minimizing transverse WSS is consistent with it having detrimental effects on the cells and with its putative role in atherogenesis.

Long-Term Serial Follow-Up of Pulmonary Artery Size and Wall Shear Stress in Fontan Patients.

Pulmonary arterial (PA) flow is abnormal after the Fontan operation and is marked by a lack of pulsatility. We assessed the effects of this abnormal flow on the size and function of the PA’s in Fontan patients in long-term serial follow-up. Twenty-three Fontan patients with serial follow-up were included. Median age was 11.1 (9.5–16.0) years at baseline and 15.5 (12.5–22.7) years at follow-up. Median follow-up duration was 4.4 (4.0–5.8) years. Flow and size of the left pulmonary artery were determined using phase-contrast MRI. From this wall shear stress (WSS), distensibility and pulsatility were determined. A group of healthy peers was included for reference. Flow and pulsatility were significantly lower in patients than in controls (p < 0.001). Mean area was comparable in patients and controls, but distensibility was significantly higher in controls (p < 0.001). Mean and peak WSS were significantly lower in Fontan patients (p < 0.001). Between baseline and follow-up, there was a significant increase in normalized flow (15.1 (14.3–19.1) to 18.7 (14.0–22.6) ml/s/m2, p = 0.023). Area, pulsatility, distensibility and WSS did not change, but there was a trend toward a lower mean WSS (p = 0.068). Multivariable regression analysis showed that flow, area and age were important predictors for WSS. WSS in Fontan patients is decreased compared to healthy controls and tends to decrease further with age. Pulsatility and distensibility are significantly lower compared to healthy controls. Pulmonary artery size, however, is not significantly different from healthy controls and long-term growth after Fontan operation is proportionate to body size.

Low Carotid Artery Wall Shear Stress is Associated with Significant Coronary Artery Disease in Patients with Chest Pain.

To investigate the relationships among carotid wall shear stress (WSS), carotid intima-media thickness (IMT), and total plaque area (TPA) using ultrasound (US) in the common carotid artery (CCA) in patients with suspected coronary artery disease (CAD). Carotid artery US was performed in 950 patients with suspected CAD, and mean IMT, TPA, and hemodynamic parameters of CCA, including peak and mean WSS, were measured. We analyzed the carotid parameters according to the presence of CAD and the predictive values of WSS and TPA for the presence of significant CAD. Compared with patients without CAD (n=667), patients with CAD (n=283) demonstrated significantly higher mean IMT (0.66 vs. 0.74 mm, p ＜ 0.001), TPA (0.13 vs. 0.20 cm(2), p=0.002), and beta stiffness index (5.12 vs. 5.60, p=0.045) and lower mean WSS (2.59 vs. 2.23 dyne/cm(2), p ＜ 0.001). Mean WSS revealed significant negative correlations with the beta stiffness index (r=-0.116, p ＜ 0.001), mean IMT (r=-0.193, p=0.007), and TPA (r =-0.296, p ＜ 0.001). Mean WSS, mean IMT and TPA revealed significant difference with respect to CAD severity (for all p ＜ 0.001). Age [OR, 1.038 (95% CI, 1.010-1.066), p=0.007], diabetes mellitus [1.606 (1.194-1.807), p= 0.011], smoking [1.758 (1.564-1.866), p ＜ 0.001], carotid TPA [2.615 (1.320-5.183), p=0.006], and mean WSS [0.554 (0.371-0.838), p=0.005] were significant CAD predictors. In patients with chest pain, low local shear stress and high plaque burden in the carotid arteries were significant CAD predictors. These findings indicate that carotid WSS has a role as an index of atherosclerosis and serves as a predictor of significant coronary atherosclerosis.

The effects of stenosis severity on the hemodynamic parameters—assessment of the correlation between stress phase angle and wall shear stress

To study the effects of increase in the degree of stenosis severity and subsequent complexity of hemodynamic patterns on hemodynamic parameters, experimental investigations and numerical simulations were performed. The correlations between the large negative Stress Phase Angle (SPA), the low mean Wall Shear Stress (WSS) and high Oscillatory Shear Index (OSI) were investigated at the distal shoulder and post-stenotic regions as the outcomes of elevated stenosis severity. Models included non-Newtonian fluid flow in stenotic arteries with 30–80% symmetrical stenoses. To study the interactions between pulsatile WSS and pulsatile wall circumferential stress (WCS) acting on endothelial cells, SPA as the phase difference between WSS and WCS waves was used. Moreover, the distribution of SPA on the lumen axis was compared to the distributions of the mean WSS and OSI that have been regarded until now as the determinants of atherosclerosis-prone regions. Results indicate that an increase in stenosis severity, not only affects the mean WSS, mean WCS and pulse amplitudes, but also influences the phase difference between them. The SPA is large negative on the distal shoulder and post-stenotic areas where atherosclerotic plaque develops. The increasing stenosis severity and the subsequent increasing complexity of hemodynamic patterns affect the correlation between any of the low mean WSS and high OSI with large negative SPA, such that it not only leads to create and develop some regions where the correlation between any of the low mean WSS and high OSI with large negative SPA is well but also leads to create and develop other regions where such correlations fail.

Comparison of Near-Wall Hemodynamic Parameters in Stented Artery Models

Four commercially available stent designs (two balloon expandable-Bx Velocity and NIR, and two self-expanding-Wallstent and Aurora) were modeled to compare the near-wall flow characteristics of stented arteries using computational fluid dynamics simulations under pulsatile flow conditions. A flat rectangular stented vessel model was constructed and simulations were carried out using rigid walls and sinusoidal velocity input (nominal wall shear stress of 10+/-5 dyn/cm2). Mesh independence was determined from convergence (<10%) of the axial wall shear stress (WSS) along the length of the stented model. The flow disturbance was characterized and quantified by the distributions of axial and transverse WSS, WSS gradients, and flow separation parameters. Normalized time-averaged effective WSS during the flow cycle was the smallest for the Wallstent (2.9 dyn/cm2) compared with the others (5.8 dyn/cm2 for the Bx Velocity stent, 5.0 dyn/cm2 for the Aurora stent, and 5.3 dyn/cm2 for the NIR stent). Regions of low mean WSS (<5 dyn/cm2) and elevated WSS gradients (>20 dyn/cm3) were also the largest for the Wallstent compared with the others. WSS gradients were the largest near the struts and remained distinctly nonzero for most of the region between the struts for all stent designs. Fully recirculating regions (as determined by separation parameter) were the largest for the Bx Velocity stent compared with the others. The most hemodynamically favorable stents from our computational analysis were the Bx Velocity and NIR stents, which were slotted-tube balloon-expandable designs. Since clinical data indicate lower restenosis rates for the Bx Velocity and NIR stents compared with the Wallstent, our data suggest that near-wall hemodynamics may predict some aspects of in vivo performance. Further consideration of biomechanics, including solid mechanics, in stent design is warranted.

Abdominal aortic hemodynamics in young healthy adults at rest and during lower limb exercise: quantification using image-based computer modeling

Localization of atherosclerotic lesions in the abdominal aorta has been previously correlated to areas of adverse hemodynamic conditions, such as flow recirculation, low mean wall shear stress, and high temporal oscillations in shear. Along with its many systemic benefits, exercise is also proposed to have local benefits in the vasculature via the alteration of these regional flow patterns. In this work, subject-specific models of the human abdominal aorta were constructed from magnetic resonance angiograms of five young, healthy subjects, and computer simulations were performed under resting and exercise (50% increase in resting heart rate) pulsatile flow conditions. Velocity fields and spatial variations in mean wall shear stress (WSS) and oscillatory shear index (OSI) are presented. When averaged over all subjects, WSS increased from 4.8 +/- 0.6 to 31.6 +/- 5.7 dyn/cm2 and OSI decreased from 0.22 +/- 0.03 to 0.03 +/- 0.02 in the infrarenal aorta between rest and exercise. WSS significantly increased, whereas OSI decreased between rest and exercise at the supraceliac, infrarenal, and suprabifurcation levels, and significant differences in WSS were found between anterior and posterior sections. These results support the hypothesis that exercise provides localized benefits to the cardiovascular system through acute mechanical stimuli that trigger longer-term biological processes leading to protection against the development or progression of atherosclerosis.

Abdominal aortic hemodynamic conditions in healthy subjects aged 50–70 at rest and during lower limb exercise: in vivo quantification using MRI

The prevalence of atherosclerosis in the abdominal aorta increases with age and is hypothesized to be related to adverse hemodynamic conditions including flow recirculation and low wall shear stress. Exercise has been shown to modulate these adverse conditions observed in the infrarenal aorta of healthy young subjects at rest. A custom magnetic resonance (MR)-compatible stationary cycle, an open MRI, and custom image processing software were used to quantify hemodynamic conditions in the abdominal aorta at rest and during cycling exercise in healthy subjects aged 50–70 years. The subjects increased their heart rate from 63±8 bpm at rest to 95±12 bpm during cycling exercise. Supraceliac blood flow increased from 2.3±0.4 to 6.0±1.4 l/min ( P<0.001) and infrarenal flow increased from 0.9±0.3 to 4.9±1.7 l/min ( P<0.001) from rest to exercise. Wall shear stress increased from 2.0±0.7 to 7.3±2.4 dynes/cm 2 at the supraceliac level ( P<0.001) and 1.4±0.8 to 16.5±5.1 dynes/cm 2 at the infrarenal level ( P<0.001) from rest to exercise. Flow and shear oscillations present at rest were eliminated during exercise. At rest, these older subjects experienced lower mean wall shear stress at the supraceliac level of the aorta and greater oscillations in wall shear stress as compared to a group of younger subjects (23.6±2.2 years). Compared to the younger subjects, the older subjects also experienced greater increases in mean wall shear stress and greater decreases in wall shear stress oscillations from rest to exercise.

Cleaning in place: effect of local wall shear stress variation on bacterial removal from stainless steel equipment

Local wall shears stress analysis as well as cleanability experiments on different pieces of equipment in various circuit arrangements were performed. Pieces of equipment used in this work, stainless steel made, were representative of production lines: straight pipes of different diameters, sudden or gradual contraction or expansion pipes. Local wall shear stress values, obtained by an electrochemical method, were shown to be influenced by the loop arrangement. Geometry as the gradual expansion pipe had an effect on the upstream straight pipe where the wall shear stress values were two times lower than in other configurations as with a sudden expansion. In sudden geometry, the bacterial removal during cleaning was improved by the increase of the flow rate, corresponding to the increase of the mean local wall shear stress. However, in gradual expansion or contraction pipe, cleanability was not improved by the increase of flow rate. The effect of the mean wall shear stress on the removal has been confirmed. Moreover, this work demonstrated a clear positive effect of an increase of the fluctuation rate on the spore detachment. Low mean wall shear stress zones as in sudden expansion (around 0.15 Pa ) could be cleanable because of the high fluctuation rate (around 21%). These results underline the importance of the design and the flow configuration.

Hemodynamic factors at the distal end-to-side anastomosis of a bypass graft with different POS:DOS flow ratios.

A pulsatile flow in vitro model of the distal end-to-side anastomosis of an arterial bypass graft was used to examine the effects that different flow ratios between the proximal outlet segment (POS) and the distal outlet segment (DOS) have on the flow patterns and the distributions of hemodynamic factors in the anastomosis. Amberlite particles were tracked by flow visualization to determine overall flow patterns and velocity measurements were made with Laser Doppler anemometry (LDA) to obtain detailed hemodynamic factors along the artery floor and the graft hood regions. These factors included wall shear stress (WSS), spatial wall shear stress gradient (WSSG), and oscillatory index (OSI). Statistical analysis was used to compare these hemodynamic factors between cases having different POS:DOS flow ratios (Case 1-0:100, Case 2-25:75, Case 3-50:50). The results showed that changes in POS:DOS flow ratios had a great influence on the flow patterns in the anastomosis. With an increase in proximal outlet flow, the range of location of the stagnation point along the artery floor decreased, while the extent of flow separation along the graft hood increased. The statistical results showed that there were significant differences (p<0.05) for the mean WSS between cases along the graft hood, but no significant differences were detected along the artery floor. There were no significant differences for the spatial WSSG along both the artery floor and the graft hood. However, there were significant differences (p<0.05) in the mean OSI between Cases 1 and 2 and between Cases 1 and 3 both along the artery floor and along the graft hood. Comparing these mechanical factors with histological findings of intimal hyperplasia formation obtained by previous canine studies, the results of the statistical analysis suggest that regions exposed to a combination of low mean WSS and high OSI may be most prone to the formation of intimal hyperplasia.

Interposition vein cuff anastomosis alters wall shear stress distribution in the recipient artery.

Interposition of a vein cuff between a prosthetic infrainguinal bypass graft and a recipient infrageniculate artery can improve graft patency. There is evidence that the improved performance may be explained by a redistribution of myointimal hyperplasia (MIH) away from the critical areas at the heel and toe of the cuff-artery anastomosis. It is widely accepted that there is an association between hemodynamic forces, more specifically, low wall shear stress (WSS), and the development of MIH. The aim of this study was to determine whether the reported redistribution of MIH in the interposition vein cuff (IVC) may be explained by differences in magnitude and distribution of WSS. Design of Study and Method: Detailed flow velocity measurements were made in life-size models of conventional end-to-side (ETS) and IVC anastomoses using a two-component laser Doppler anemometer under pulsatile flow conditions. Velocity vectors were determined in the plane of symmetry of the anastomosis, and the variation of WSS was estimated from near-wall velocity measurements on the floor and upper wall of the artery. The main flow features in the ETS anastomosis were flow separation at the graft hood, strong radial velocity at the heel, and a stagnation point on the floor of the artery that moved slightly during the flow cycle. In the IVC anastomosis, a coherent vortex that occupied most of the cuff volume was present from the systolic deceleration phase to end diastole. A stagnation point on the anastomosis floor was found to oscillate by about 4 mm. Critical regions of low mean WSS (ie, below 0.5 N/m(2)) were identified. In the ETS anastomosis, they were found at the heel and along the floor. In the IVC anastomosis, low mean WSS was found only on the floor, and it was generally less extensive than in the ETS anastomosis. The vein cuff anastomosis alters the mean WSS distribution within the recipient artery and removes the area of low WSS at the heel. This may explain the redistribution of MIH away from important sites in the recipient artery.

In the femoral artery bifurcation, differences in mean wall shear stress within subjects are associated with different intima-media thicknesses.

In elastic arteries, intima-media thickening is more pronounced in areas with low than with high mean and peak wall shear stress. These findings in elastic arteries are not necessarily representative of the situation in muscular arteries. The former arteries have to store volume energy, whereas the latter are mainly conductive vessels. It was the aim of the present study to investigate noninvasively whether differences in wall shear stress within a muscular artery bifurcation, if any, were associated with different intima-media thicknesses (IMTs). The effect of age on the possible differences was assessed as well. We determined IMT and mean, peak systolic, and the maximum cyclic change in shear stress near the posterior wall in the common (FC) and the superficial (FS) femoral artery 20 to 30 mm from the flow divider in 54 presumed healthy subjects between 21 and 74 years of age. Results were considered in terms of intrasubject differences. Before the study, the reliability of the ultrasonic system to assess wall shear rate and IMT was determined in terms of intrasubject variability. IMT at the posterior wall was significantly larger in the FC than in the FS, probably owing to the significantly lower mean wall shear stress at this site in the FC. The relative differences in IMT and mean wall shear stress between FC and FS were independent of age. The difference in wall shear stress between both arteries can likely be explained by a different influence of reflections. In both the FC and FS, mean, peak systolic, and maximum cyclic change in shear stress near the posterior wall did not change significantly with age, whereas IMT did increase significantly with age.

Influence of vasoactive drugs on wall shear stress distribution in the abdominal aortic bifurcation: an in vitro study.

The present study compares the wall shear stress (rate) distribution in a compliant aortic bifurcation model under three different hemodynamic states: normal state, angiotensin II infusion state (vasoconstrictor), and isoproterenol infusion state (vasodilator). Using a Newtonian blood analog fluid, flow wave forms corresponding to each flow state were generated in an in vitro flow loop and a photographic flow visualization technique was employed to measure wall shear rate. The results indicate a zone of low mean wall shear stress and highly oscillatory shear stress on the outer (lateral) wall of the bifurcation. In this zone, the mean wall shear stress became negative for all three hemodynamic states indicating flow separation. However, the spatial extent of the flow separation zone was not affected significantly by the flow state. The study also revealed a large spatial variation of the phase angle between the hoop strain (circumferential strain due to radial artery expansion) and the wall shear stress, the two main mechanical stimuli acting on endothelial cells which affect their biology. In the zone of low mean wall shear stress on the outer wall, the two stimuli were more out of phase relative to the mother branch, whereas they were less out of phase (by about 50 degrees) on the inner wall (flow divider side). This phase angle was affected significantly by the flow state. For angiotensin II, the phase angle reached a maximum of 125 degrees in the low mean shear zone while the maximum was 94 degrees and 66 degrees for the normal and isoproterenol states, respectively. Our observation that large phase angles between the hoop strain and wall shear stress wave forms are localized in the low shear stress region where atherosclerotic disease occurs suggests the possible physiological relevance of this phase angle to the development of atherosclerosis.