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Endothelial shear stress is a tangential stress derived from the friction of the flowing blood on the endothelial surface of the arterial wall and is expressed in units of force/unit area (dyne/cm2). Branches and bends of arteries are exposed to complex blood flow patterns that generate low or oscillatory endothelial shear stress, which impairs glycocalyx integrity, cytoskeleton arrangement and endothelial junctions (adherens junctions, tight junctions, gap junctions), thus increasing endothelial permeability. The lipoproteins and inflammatory cells penetrating intima due to the increased endothelial permeability characterizes the pathological changes in early stage of atherosclerosis. Endothelial cells are critical sensors of shear stress, however, the mechanisms by which the complex shear stress regulate endothelial permeability in atherosclerosis remain unclear. In this review, we focus on the molecular mechanisms of the endothelial permeability induced by low or oscillatory shear stress, which will shed a novel sight in early stage of atherosclerosis. [ABSTRACT FROM AUTHOR]

Intracranial aneurysms (IAs) pose severe health risks influenced by hemodynamics. This study focuses on the intricate characterization of hemodynamic conditions within the IA walls and their influence on bleb development, aiming to enhance understanding of aneurysm stability and the risk of rupture. The methods emphasized utilizing a comprehensive dataset of 359 IAs and 213 IA blebs from 268 patients to reconstruct patient‐specific vascular models, analyzing blood flow using finite element methods to solve the unsteady Navier–Stokes equations, the segmentation of aneurysm wall subregions and the hemodynamic metrics wall shear stress (WSS), its metrics, and the critical points in WSS fields were computed and analyzed across different aneurysm subregions defined by saccular, streamwise, and topographical divisions. The results revealed significant variations in these metrics, correlating distinct hemodynamic environments with wall features on the aneurysm walls, such as bleb formation. Critical findings indicated that regions with low WSS and high OSI, particularly in the body and central regions of aneurysms, are prone to conditions that promote bleb formation. Conversely, areas exposed to high WSS and positive divergence, like the aneurysm neck, inflow, and outflow regions, exhibited a different but substantial risk profile for bleb development, influenced by flow impingements and convergences. These insights highlight the complexity of aneurysm behavior, suggesting that both high and low‐shear environments can contribute to aneurysm pathology through distinct mechanisms. [ABSTRACT FROM AUTHOR]

The inferior vena cava filter (IVCF) has been used in clinical practice for decades to prevent fatal pulmonary embolism. One of the most commonly used types of IVCFs features a conical umbrella-like design. The geometric similarity among these umbrella-shaped IVCFs suggests a potential commonality in their hemodynamic behavior. However, many previous studies have primarily analyzed the blood flow around a single umbrella-shaped IVCF, failing to capture the general hemodynamic characteristics of this filter type. This paper uses computational fluid dynamics to simulate the blood flow around five typical umbrella-shaped IVCFs, aiming to investigate their hemodynamic commonality. For all five IVCFs, prothrombotic stagnation zones are observed downstream of the filter head, extending nearly 12 times the diameter of the inferior vena cava (IVC). The "viscous block" effect of the filter wires accelerates blood flow within the conical region of the filter, enhancing the potential for clot capture and dissolution. The deployment of umbrella-shaped IVCF remarkably increases the wall shear stress (WSS) on the IVC wall, and the WSS on the filter wire continuously increases in the flow direction. Additionally, the viscous resistance of each umbrella-shaped IVCF contributes several times more to the total flow resistance than the pressure resistance. Our results suggest that alterations in the morphology of the filter wires of umbrella-shaped IVCFs significantly impact the flow resistance of the filter and the WSS distribution pattern of the IVC. These hemodynamic changes may lead to life-threatening conditions, such as IVC lesions, filter rupture, and displacement. [ABSTRACT FROM AUTHOR]

The vast majority of heart attacks occur when vulnerable plaques rupture, releasing their lipid content into the blood stream leading to thrombus formation and blockage of a coronary artery. Detection of these unstable plaques before they rupture remains a challenge. Hemodynamic features including wall shear stress (WSS) and wall shear stress gradient (WSSG) near the vulnerable plaque and local inflammation are known to affect plaque instability. In this work, a computational workflow has been developed to enable a comprehensive parametric study detailing the effects of 3D plaque shape on local hemodynamics and their implications for plaque instability. Parameterized geometric 3D plaque models are created within a patient-specific coronary artery tree using a NURBS (non-uniform rational B-splines)-based vascular modeling pipeline. Realistic blood flow features are simulated by using a Navier–Stokes solver within an isogeometric finite-element analysis framework. Near wall hemodynamic quantities such as WSS and WSSG are quantified, and vascular distribution of an inflammatory marker (VCAM-1) is estimated. Results show that proximally skewed eccentric plaques have the most vulnerable combination of high WSS and high positive spatial WSSG, and the presence of multiple lesions increases risk of rupture. The computational tool developed in this work, in conjunction with clinical data, -could help identify surrogate markers of plaque instability, potentially leading to a noninvasive clinical procedure for the detection of vulnerable plaques before rupture. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a condition which disrupts blood flow due to plaque build-up inside the arteries. Under conditions where consecutive plaques are prevailing blood hammer principle is exhibited. The pressure and shear stress produced at an infinitesimal area act as the governing equation for stent modeling. The leading order pressure lays the foundation for the design of cardiac stents with definite dimensions. The designed stent was encapsulated inside a crimper validated through ANSYS-static and transient structural simulation to derive the total deformation, equivalent strain, and stress exerted on the stent. Five different biomaterials stainless steel 316, cobalt, chromium, platinum, and Poly lactic acid were selected for the material assessment. Static and Transient structural analysis for a period of 1 and 10 secs was implemented for a stent with and without a crimper. The material performance in terms of total deformation, equivalent stress, and strain are analyzed. The paper envisions the dynamics of blood hammer in atherosclerosis that provides the changes in the pressure and clotting process. It shows the promising results of the stent behavior in varied forces which gives valuable insights for future improvement in stent design and material selection. [ABSTRACT FROM AUTHOR]

Background: In recent years, intravascular micro-axial blood pumps have been increasingly used in the treatment of patients with cardiogenic shock. The flow rate of such blood pumps requires adjustment based on the patient's physiological condition. Compared to a stable flow state with fixed rotation speed, adjusting the speed of blood pump impeller to alter flow rate may lead to additional hemolysis. This study aimed at elucidating the relationship between adjusting interval of a blood pump's impeller speed and the hemolysis index. Methods: By comparing simulation results with P-Q characteristic curves of the blood pump measured by experiments, the accuracy of the blood pump flow field simulation model was confirmed. In this study, a drainage tube was employed as the device analogous to an intravascular micro-axial blood pump for achieving similar shear stress levels and residence times. The hemolysis finite element prediction method based on a power-law model was validated through hemolysis testing of porcine blood flow through the drainage tube. The validated models were subsequently utilized to investigate the impact of impeller speed adjusting intervals on hemolysis in the blood pump. Results: Compared to steady flow, the results demonstrate that the hemolysis index increased to 6.3% when changing the blood pump flow rate from 2 L/min to 2.5 L/min by adjusting the impeller speed within 0.072 s. Conclusions: An adjustment time of impeller speed longer than 0.072 s can avoid extra hemolysis when adjusting the intravascular micro-axial blood pump flow rate from 2 L/min to 2.5 L/min. [ABSTRACT FROM AUTHOR]

Atherosclerosis is an inflammatory reaction that develops at specific regions within the artery wall and at specific sites of the arterial tree over a varying time frame in response to a variety of risk factors. The mechanisms that account for the interaction of systemic factors and atherosclerosis-susceptible regions of the arterial tree to mediate this site-specific development of atherosclerosis are not clear. The dynamics of blood flow has a major influence on where in the arterial tree atherosclerosis develops, priming the site for interactions with atherosclerotic risk factors and inducing cellular and molecular participants in atherogenesis. But how this accounts for lesion development at various locations along the vascular tree across differing time frames still requires additional study. Currently, murine models are favored for the experimental study of atherogenesis and provide the most insight into the mechanisms that may contribute to the development of atherosclerosis. Based largely on these studies, in this review, we discuss the role of hemodynamic shear stress, SR-B1, and other factors that may contribute to the site-specific development of atherosclerosis. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a cardiovascular disease caused by the enlargement of the aorta in the abdomen over time. Unless treated, the growth of AAA continues, resulting in 80% death in the case of rupture. Today, the width of the aneurysm diameter is taken into account in clinical practice to examine the status of AAA. Although there are aneurysms that do not rupture despite reaching a diameter of 9 cm, it is reported that aneurysms with a diameter of 3 cm are ruptured in several cases. Therefore, analyzing only the AAA diameter is not a reliable method, and a deeper investigation is necessary for the rupture risk assessment. In this study, a patient's situation is analyzed using computational fluid dynamics (CFD) simulations, which allows to elucidate the flow dependent parameters such as velocity, vorticity, pressure, and wall shear stress (WSS). First, the patient-specific geometry was obtained and boundary conditions were defined at the inlet and the outlet of the flow domain. The effects of intraluminal thrombus (ILT) formation and patient’s effort conditions were also included in the analysis. According to the results, WSS and vorticity increase with the increasing blood flow velocity. In terms of the rupture risk, it has been found that the effect of patient’s effort level is more critical than the amount of ILT in the AAA. [ABSTRACT FROM AUTHOR]

Molecular characterization of vascular anomalies has revealed that affected endothelial cells (ECs) harbor gain-of-function (GOF) mutations in the gene encoding the catalytic a subunit of PI3Ka (PIK3CA). These PIK3CA mutations are known to cause solid cancers when occurring in other tissues. PIK3CA-related vascular anomalies, or "PIKopathies," range from simple, i.e., restricted to a particular form of malformation, to complex, i.e., presenting with a range of hyperplasia phenotypes, including the PIK3CArelated overgrowth spectrum. Interestingly, development of PIKopathies is affected by fluid shear stress (FSS), a physiological stimulus caused by blood or lymph flow. These findings implicate PI3K in mediating physiological EC responses to FSS conditions characteristic of lymphatic and capillary vessel beds. Consistent with this hypothesis, increased PI3K signaling also contributes to cerebral cavernous malformations, a vascular disorder that affects low-perfused brain venous capillaries. Because the GOF activity of PI3K and its signaling partners are excellent drug targets, understanding PIK3CA's role in the development of vascular anomalies may inform therapeutic strategies to normalize EC responses in the diseased state. This Review focuses on PIK3CA's role in mediating EC responses to FSS and discusses current understanding of PIK3CA dysregulation in a range of vascular anomalies that particularly affect low-perfused regions of the vasculature. We also discuss recent surprising findings linking increased PI3K signaling to fast-flow arteriovenous malformations in hereditary hemorrhagic telangiectasias. [ABSTRACT FROM AUTHOR]

The influence of the aneurysm evolution on the hemodynamic characteristic of the blood flow inside the sac region is comprehensively investigated. By using the computational method, the blood flow through the vessel and aneurysm of the sac region is examined to find the role of aneurysm evolution on the wall shear stress, pressure, and risk of aneurysm rupture. Three different models of ICA aneurysms are chosen for the investigation of the aneurysm evolution at risk of rupture. Obtained data shows that the evolution of the aneurysm decreases the wall shear stress and pressure on the sac surface while an oscillatory index of blood increases on the aneurysm wall. [ABSTRACT FROM AUTHOR]

It is well‐recognized that blood flow at branches and bends of arteries generates disturbed shear stress, which plays a crucial in driving atherosclerosis. Flow‐generated fluid shear stress (FSS), as one of the key hemodynamic factors, is appreciated for its critical involvement in regulating angiogenesis to facilitate wound healing and tissue repair. Endothelial cells can directly sense FSS but the mechanobiological mechanism by which they decode different patterns of FSS to trigger angiogenesis remains unclear. In the current study, laminar shear stress (LSS, 15 dyn/cm2) was employed to mimic physiological blood flow, while disturbed shear stress (DSS, ranging from 0.5 ± 4 dyn/cm2) was applied to simulate pathological conditions. The aim was to investigate how these distinct types of blood flow regulated endothelial angiogenesis. Initially, we observed that DSS impaired angiogenesis and downregulated endogenous vascular endothelial growth factor B (VEGFB) expression compared to LSS. We further found that the changes in membrane protein, migration and invasion enhancer 1 (MIEN1) play a role in regulating ERK/MAPK signaling, thereby contributing to endothelial angiogenesis in response to FSS. We also showed the involvement of MIEN1‐directed cytoskeleton organization. These findings suggest the significance of shear stress in endothelial angiogenesis, thereby enhancing our understanding of the alterations in angiogenesis that occur during the transition from physiological to pathological blood flow. [ABSTRACT FROM AUTHOR]

A variety of circulatory disorders can be brought on by stenosis, which restricts a bodily passage artery or orifice. It may cause of brain disorders, heart diseases and legs disabilities. With the assistance of the Prandtl fluid model, the present investigation proposes an analytical strategy for monitoring blood flow through a stenosed artery. The artery is depicted as a tube with a cross-sectional view of an ellipse form. The flow-regulating equations are derived in the dimensionless form under the assumption of mild stenosis. The solution of mathematical equations is obtained by employing the perturbation technique via polynomial of degree four. It is analyzed graphically how flow-related parameters such as artery length L, stenosis height δ l , fluid parameters α , and K influence the velocity distribution, wall shear stress, and flow resistance. It is observed that the non-Newtonian effects dominate in the surrounding stenosed wall of the artery along the minor axis. The wall shear stress is found to attain its maximum value at the peak of stenosis. The height of stenosis considerably impacts the flow resistance, and as it increases, so does the opposition, which develops the disorder in the confined area. The streamlines are also plotted to analyze the flow behavior, and it is observed that the contours are produced in the constricted zone. [ABSTRACT FROM AUTHOR]

Recent clinical data indicate a different performance of biodegradable polymer (BP)-drug eluting stent (DES) compared to durable polymer (DP)-DES. Whether this can be explained by a beneficial impact of BP-DES stent design on the local hemodynamic forces distribution remains unclear. To compare endothelial shear stress (ESS) distribution after implantation of ultrathin (us) BP-DES and DP-DES and examine the association between ESS and neointimal thickness (NIT) distribution in the two devices at 9 months follow up. We retrospectively identified patients from the BIOFLOW II trial that had undergone OCT imaging. OCT data were utilized to reconstruct the surface of the stented segment at baseline and 9 months follow-up, simulate blood flow, and measure ESS and NIT in the stented segment. The patients were divided into 3 groups depending on whether DP-DES (N = 8, n = 56,160 sectors), BP-DES with a stent diameter of >3 mm (strut thickness of 80 μm, N = 6, n = 36,504 sectors), or BP-DES with a stent diameter of ≤3 mm (strut thickness of 60 μm, N = 8, n = 50,040 sectors) were used for treatment. The ESS, and NIT distribution and the association of these two variables were estimated and compared among the 3 groups. In the DP-DES group mean NIT was 0.18 ± 0.17 mm and ESS 1.68 ± 1.66 Pa; for the BP-DES ≤3 mm group the NIT was 0.17 ± 0.11 mm and ESS 1.49 ± 1.24 Pa and for the BP-DES >3 mm group 0.20 ± 0.23 mm and 1.42 ± 1.24 Pa respectively (p < 0.001 for both NIT and ESS comparisons across groups). A negative correlation between NIT and baseline ESS was found, the correlation coefficient for all the stented segments was −0.33, p < 0.001. In this OCT sub-study of the BIOFLOW II trial, the NIT was statistically different between groups of patients treated with BP-DES and DP-DES. In addition, regions of low ESS were associated with increased NIT in all studied devices. • This is the first study that evaluates, compares, and relates neointimal thickness (NIT) with endothelial shear stress (ESS) in biodegradable polymer drug-eluting stents versus traditional 2nd generation durable polymer drug-eluting stents. • Neo-intimal thickness in the stented segment was different in biodegradable polymer drug-eluting stents versus 2nd generation durable polymer drug-eluting stents. • This difference was statistically significant, but marginal and may not be clinically relevant. • A negative correlation was seen between endothelial shear stress and neointimal thickness as regions of low ESS were associated with increased NIT. [ABSTRACT FROM AUTHOR]

The endothelial glycocalyx encompasses the entire endothelial cell, transducing extracellular signals and regulating vascular permeability and barrier functions. The apical glycocalyx, which forms the lumen of the vessel, and the basal glycocalyx, at the smooth muscle cell interface, are often investigated separately as they are exposed to vastly different stimuli. The apical glycocalyx directly senses fluid shear forces transmitting them intracellularly through connection to the cytoskeleton of the endothelial cell. The basal glycocalyx has demonstrated sensitivity to shear due to blood flow transmitted through the cytoskeleton, promoting alternate signaling processes. In this review, we discuss current literature on the basal glycocalyx's response to shear stress in the context of mechanotransduction and remodeling. The possible implications of basal glycocalyx degradation in pathologies are also explored. Finally, this review seeks to highlight how addressing the gaps discussed would improve our wholistic understanding of the endothelial glycocalyx and its role in maintaining vascular homeostasis. [ABSTRACT FROM AUTHOR]

The endovascular neural interface provides an appealing minimally invasive alternative to invasive brain electrodes for recording and stimulation. However, stents placed in blood vessels have long been known to affect blood flow (haemodynamics) and lead to neointimal growth within the blood vessel. Both the stent elements (struts and electrodes) and blood vessel wall geometries can affect the mechanical environment on the blood vessel wall, which could lead to unfavourable vascular remodelling after stent placement. With increasing applications of stents and stent-like neural interfaces in venous blood vessels in the brain, it is necessary to understand how stents affect blood flow and tissue growth in veins. We explored the haemodynamics of a stent-mounted neural interface in a blood vessel model. Results indicated that blood vessel deformation and tapering caused a substantial change to the lumen geometry and the haemodynamics. The neointimal proliferation was evaluated in sheep implanted with an endovascular neural interface. Analysis showed a negative correlation with the mean Wall Shear Stress pattern. The results presented here indicate that the optimal stent oversizing ratio must be considered to minimise the haemodynamic impact of stenting. [ABSTRACT FROM AUTHOR]

Preclinical human‐relevant modeling of organ‐specific vasculature offers a unique opportunity to recreate pathophysiological intercellular, tissue‐tissue, and cell‐matrix interactions for a broad range of applications. Here, this work presents a reliable, and simply reproducible process for constructing user‐controlled long rounded extracellular matrix (ECM) embedded vascular microlumens on‐chip for endothelization and co‐culture with stromal cells obtained from human lung. This work demonstrates the critical impact of microchannel cross‐sectional geometry and length on uniform distribution and magnitude of vascular wall shear stress, which is key when emulating in vivo observed blood flow biomechanics in health and disease. In addition, this study provides an optimization protocol for multicellular culture and functional validation of the system. Moreover, this study shows the ability to finely tune rheology of the three‐dimensional natural matrix surrounding the vascular microchannel to match pathophysiological stiffness. In summary, this work provides the scientific community with a matrix‐embedded microvasculature on‐chip populated with all‐primary human‐derived pulmonary endothelial cells and fibroblasts to recapitulate and interrogate lung parenchymal biology, physiological responses, vascular biomechanics, and disease biogenesis in vitro. Such a mix‐and‐match synthetic platform can be feasibly adapted to study blood vessels, matrix, and ECM‐embedded cells in other organs and be cellularized with additional stromal cells. [ABSTRACT FROM AUTHOR]

The heart is a metabolic "omnivore" and adjusts its energy source depending on the circulating metabolites. Human cardiac organoids, a three-dimensional in vitro model of the heart wall, are a useful tool to study cardiac physiology and pathology. However, cardiac tissue naturally experiences shear stress and nutrient fluctuations via blood flow in vivo, whilst in vitro models are conventionally cultivated in a static medium. This necessitates the regular refreshing of culture media, which creates acute cellular disturbances and large metabolic fluxes. To culture human cardiac organoids in a more physiological manner, we have developed a perfused bioreactor for cultures in a 96-well plate format. The designed bioreactor is easy to fabricate using a common culture plate and a 3D printer. Its open system allows for the use of traditional molecular biology techniques, prevents flow blockage issues, and provides easy access for sampling and cell assays. We hypothesized that a perfused culture would create more stable environment improving cardiac function and maturation. We found that lactate is rapidly produced by human cardiac organoids, resulting in large fluctuations in this metabolite under static culture. Despite this, neither medium perfusion in bioreactor culture nor lactate supplementation improved cardiac function or maturation. In fact, RNA sequencing revealed little change across the transcriptome. This demonstrates that cardiac organoids are robust in response to fluctuating environmental conditions under normal physiological conditions. Together, we provide a framework for establishing an easily accessible perfusion system that can be adapted to a range of miniaturized cell culture systems. [ABSTRACT FROM AUTHOR]

Due to their effect on aneurysm hemodynamics, flow diverters (FD) have become a routine endovascular therapy for intracranial aneurysms. Since over- and undersizing affect the device's hemodynamic abilities, selecting the correct device diameter and accurately simulating FD placement can improve patient-specific outcomes. The purpose of this study was to validate the accuracy of virtual flow diverter deployments in the novel Derivo® 2 device. We retrospectively analyzed blood flows in ten FD placements for which 3D DSA datasets were available pre- and post-intervention. All patients were treated with a second-generation FD Derivo® 2 (Acandis GmbH, Pforzheim, Germany) and post-interventional datasets were compared to virtual FD deployment at the implanted position for implanted stent length, stent diameters, and curvature analysis using ANKYRAS (Galgo Medical, Barcelona, Spain). Image-based blood flow simulations of pre- and post-interventional configurations were conducted. The mean length of implanted FD was 32.61 (±11.18 mm). Overall, ANKYRAS prediction was good with an average deviation of 8.4% (±5.8%) with a mean absolute difference in stent length of 3.13 mm. There was a difference of 0.24 mm in stent diameter amplitude toward ANKYRAS simulation. In vessels exhibiting a high degree of curvature, however, relevant differences between simulated and real-patient data were observed. The intrasaccular blood flow activity represented by the wall shear stress was qualitatively reduced in all cases. Inflow velocity decreased and the pulsatility over the cardiac cycle was weakened. Virtual stenting is an accurate tool for FD positioning, which may help facilitate flow FDs' individualization and assess their hemodynamic impact. Challenges posed by complex vessel anatomy and high curvatures must be addressed. [ABSTRACT FROM AUTHOR]

How do vessels find optimal radii? Capillaries are known to adapt their radii to maintain the shear stress of blood flow at the vessel wall at a set point, yet models of adaptation purely based on average shear stress have not been able to produce complex loopy networks that resemble real microvascular systems. For narrow vessels where red blood cells travel in a single file, the shear stress on vessel endothelium peaks sharply when a red blood cell passes through. We show that stable shear-stress-based adaptation is possible if vessel shear stress set points are cued to the stress peaks. Model networks that respond to peak stresses alone can quantitatively reproduce the observed zebrafish trunk microcirculation, including its adaptive trajectory when hematocrit changes or parts of the network are amputated. Our work reveals the potential for mechanotransduction alone to generate stable hydraulically tuned microvascular networks. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a serious dilated vascular disease. The risk factors of aneurysm rupture and postoperative blood pressure are the major clinical concerns. The purpose of this work is to analyze the hemodynamic difference between preoperative and postoperative AAA using patient-specific boundary conditions and explore the rupture risk of AAA with different torsion and to simulate the blood flow of different degrees of hypertension. A three-element Windkessel model is utilized as the outlet boundary condition. 20-sim software and self-developed user-defined functions are used to calibrate the parameters. To analyze the influence of aortic tortuosity on hemodynamics, five AAA geometries with different torsion degrees are modified and obtained. We also grade the hypertension and explore the effect of hypertension after operation. The analysis results are consistent with the patient-specific situation. The results show that stent implantation for aneurysms reduces the pressure at the lesion site and increase the speed and wall shear stress. Vessels with high torsion have lower time-averaged wall shear stress (TAWSS), higher oscillatory shear stress index (OSI) and relative retention time, and more disordered blood flow. After stent implantation, with the increase in blood pressure, TAWSS and OSI continue to increase, and the blood flow speed is also faster. AAA with high torsion is more likely to rupture. In clinical practice, attention should be paid to the degree of torsion of the lesion site. Furthermore, blood pressure should be monitored and controlled in time to prevent postoperative complications. [ABSTRACT FROM AUTHOR]

Thrombosis is a complex biological process which involves many biochemical reactions and is influenced by blood flow. Various computational models have been developed to simulate natural thrombosis in diseases such as aortic dissection (AD), and device-induced thrombosis in blood-contacting biomedical devices. While most hemodynamics-based models consider the role of low shear stress in the initiation and growth of thrombus, they often ignore the effect of thrombus breakdown induced by elevated shear stress. In this study, a new shear stress-induced thrombus breakdown function is proposed and implemented in our previously published thrombosis model. The performance of the refined model is assessed by quantitative comparison with experimental data on thrombus formation in a backward-facing step geometry, and qualitative comparison with in vivo data obtained from an AD patient. Our results show that incorporating thrombus breakdown improves accuracy in predicted thrombus volume and captures the same pattern of thrombus evolution as measured experimentally and in vivo. In the backward-facing step geometry, thrombus breakdown impedes growth over the step and downstream, allowing a stable thrombus to be reached more quickly. Moreover, the predicted thrombus volume, height and length are in better agreement with the experimental measurements compared to the original model which does not consider thrombus breakdown. In the patient-specific AD, the refined model outperforms the original model in predicting the extent and location of thrombosis. In conclusion, the effect of thrombus breakdown is not negligible and should be included in computational models of thrombosis. [ABSTRACT FROM AUTHOR]

Purpose: Coronary stenting to remove plaque and easing blood flow through major arteries is a standard surgical procedure. Methods: The present paper utilizes the CAD model of a stent based on the BX-Velocity stent design and analyses the flow parameters resulting after its placement within the artery under different conditions. This stent geometry is placed within a bifurcated artery. A pulsatile blood flow regime is considered along with three different positions (A, B and C) of the stent within the artery. Results: The results of the fluid flow analysis show that position B is the most favourable for the placement of the stent. The resultant wall shear stresses (time-averaged) and the wall shear stress gradient magnitudes indicate the possibility of developing neointimal hyperplasia for position B. Conclusions: The present study aims to mimic the pulsatile blood flow within a branched artery and the results indicate that the position B of the stent within a bifurcating artery can lead to the best possible outcome. [ABSTRACT FROM AUTHOR]

The analysis of blood flow in the stenotic artery is imperative as the existence and progression of stenosis effectively disturbs the blood flow in the artery, which may cause vascular disease. In this study, we considered the linearized Phan-Thien–Tanner (PTT) fluid model to study the non-Newtonian nature of blood flow in the stenosed artery inclined at an angle γ. The artery is considered to have multiple stenoses and a cross-section of elliptical shape. The PTT model is appropriate for this analysis as viscoelastic properties and shear-thinning characteristics characterize it. The elliptical cross-section of the artery raises the nonlinearity of the mathematical model and makes it effortful to solve the equations analytically. The mathematical equations of the model are processed to non-dimensional form under the assumptions of mild stenosis, which help us to get the exact solutions of the equations in the elliptical domain. The analytically acquired solutions are investigated in detail by their graphical interpretation. It is analyzed that progressive height of stenosis generates the more significant disorder in the narrowed part of the channel as the velocity reverses its behavior in that region. The advancing values of the Weissenberg number, Grashof number and extensional and heat source parameters cause to lessen the axial velocity and slow the fluid flow. The rising Grashof number has nearly no impact on the velocity in the center of the channel. The wall shear stress aggrandizes with the growth of stenosis height, and its behavior for other physical constraints is similar to the flow velocity. It also has a practical enhancement in the stenotic region of the conduit. It is observed that fluid velocity and wall shear stress have larger values for zero angles of inclination than the inclination angle of 9 0 ∘ . The streamlined examination indicates the generation of the vortices in the stenotic part of the artery. Moreover, the flow velocity and wall shear stress have lower values for the nonuniform shape than for the uniform form of stenosis. [ABSTRACT FROM AUTHOR]

Purpose: Iliac vein stenting is the primary treatment for patients with iliac vein compression syndrome (IVCS). However, post-stent placement, patients often experience in-stent restenosis and thrombosis. Despite this, the role of lower limb movements in the functioning of stents and veins in IVCS patients remains unclear. This study aimed to address this knowledge gap by developing a computational model using medical imaging techniques to simulate IVCS after stent placement. Methods: This research used a patient-specific model to analyze the effects of lower extremity exercises on hemodynamics post-stent placement. We conducted a comprehensive analysis to evaluate the impact of specific lower limb movements, including hip flexion, ankle movement and pneumatic compression on the hemodynamic characteristics within the treated vein. The analysis assessed parameters such as wall shear stress (WSS), oscillatory shear index (OSI), and residence time (RRT). Results: The results demonstrated that hip flexion significantly disrupts blood flow dynamics at the iliac vein bifurcation after stenting. Bilateral and left hip flexion were associated with pronounced regions of low WSS and high OSI at the iliac-vena junction and the stent segment. Additionally, active ankle exercise (AAE) and intermittent pump compression (IPC) therapy were found to enhance the occurrence of low WSS regions along the venous wall, potentially reducing the risk of thrombosis poststent placement. Consequently, both active joint movements (hip and ankle) and passive movements have the potential to influence the local blood flow environment within the iliac vein after stenting. Conclusions: The exploration of the impact of lower limb movements on hemodynamics provides valuable insights for mitigating adverse effects associated with lower limb movements post iliac-stenting. Bilateral and left hip flexions negatively impacted blood flow, increasing thrombosis risk. However, active ankle exercise and intermittent pump compression therapies effectively improve the patency. [ABSTRACT FROM AUTHOR]

Blood is a sophisticated biological fluid with components like erythrocytes that give it non-Newtonian behavior. Hemodynamic factors such as velocity magnitude, pressure, and wall shear stress descriptors are the most important factors in the development of atherosclerosis. The wall shear stress descriptors are regulated not only by flow geometry but also by blood rheological properties. In the current study, we carried out a numerical analysis of the non-Newtonian pulsatile blood flow while taking into account a patient-specific geometry and transient boundary conditions. Non-Newtonian blood flow is modeled using the four non-Newtonian models: the power-law model, the Carreau model, the Casson model, and the Quemada model, and compared with the Newtonian model. Streamline analysis vividly illustrates velocity patterns, revealing the presence of recirculation zones near sinus regions. The study suggests the significance of selecting appropriate viscosity models for accurate assessments, particularly in regions with low time-average wall shear stress values, such as those associated with atherosclerotic plaques. The differences in the time-averaged wall shear stress between the four non-Newtonian models were found to be the highest in the Quemada model. The study concluded that the non-Newtonian model is required when the focus is on the low-time-averaged wall shear stress area. [ABSTRACT FROM AUTHOR]

Diabetes-related vascular abnormalities are commonly encountered in the retinal vasculature, the most common being the increased tortuosity and reduced lumen diameter. These morphological changes significantly affect the underlying hemodynamics and remain unexplored. The current study examines the changes produced by the altered morphology on the blood flow velocity and wall shear stress (WSS) using particle streak velocimetry (PSV) experiments and numerical simulations and compares it with the healthy scenario. The diabetic and healthy retinal arteries are extracted from patient-specific fundus images and transparently printed using stereolithography (SLA) in three dimensions. Flow visualization experiments are performed using the blood-mimicking fluid (BMF) with three different flow rates, whose values are evaluated using the similarity analysis. Experimental and simulation results illustrate a significant reduction in the average axial velocity and WSS due to tortuosity with maximum percentage reductions of 10% and 11%, respectively, compared to healthy. Additionally, a strong correlation is observed between a particular artery's local tortuosity and the WSS, with a higher tortuosity index leading to the development of low-shear regions inside the diabetic artery. A 14% diameter reduction in the diabetic arteries leads to approximately 65% and 63% increase in the velocity and WSS, respectively, compared to healthy. Moreover, the experiments also capture the effect of decreased blood viscosity on the WSS in the case of diabetic arteries, illustrating a significant decrease in WSS values. The experiments performed in the current study may help ophthalmologists estimate the induced damage that the arterial morphological changes may create and facilitate an accurate prognosis of retinal vascular diseases. [ABSTRACT FROM AUTHOR]

Massive trauma remains a leading cause of death and a global public health burden. Post-traumatic coagulopathy may be present even before the onset of resuscitation, and correlates with severity of trauma. Several mechanisms have been proposed to explain the development of abnormal coagulation processes, but the heterogeneity in injuries and patient profiles makes it difficult to define a dominant mechanism. Regardless of the pattern of death, a significant role in the pathophysiology and pathogenesis of coagulopathy may be attributed to the exposure of endothelial cells to abnormal physical forces and mechanical stimuli in their local environment. In these conditions, the cellular responses are translated into biochemical signals that induce/aggravate oxidative stress, inflammation, and coagulopathy. Microvascular shear stress-induced alterations could be treated or prevented by the development and use of innovative pharmacologic strategies that effectively target shear-mediated endothelial dysfunction, including shear-responsive drug delivery systems and novel antioxidants, and by targeting the venous side of the circulation to exploit the beneficial antithrombogenic profile of venous endothelial cells. [ABSTRACT FROM AUTHOR]

This study investigates the hemodynamic impacts of localized aortic valve calcification, utilizing immersed boundary-finite element (IBFE) method simulations with realistic inflow patterns of uniform and helical blood flow from the left ventricular outflow tract (LVOT). We modeled the aortic valve leaflets with varying grades of calcification, assessing their influence on valve performance, including transvalvular hemodynamics, wall shear stress (WSS) indices, and vortical structures. The findings highlighted that calcification significantly restricts leaflet motion, diminishes the orifice area, disrupts flow efficiency, and consequently increases the left ventricular workload. Advanced calcification resulted in elevated WSS, especially at the leaflet tips, which indicates a heightened risk of endothelial damage and further calcification. Asymmetrical calcifications redirect flow towards the ascending aorta wall, potentially inducing structural damage and increased stress on the remaining healthy leaflets. Calcification was also found to alter the naturally occurring helical blood flow patterns, affecting the system's fluid transport efficiency and possibly contributing to cardiovascular disease progression. The study revealed a significant alteration in vortex formation, with calcification causing distorted and complex vortex structures, which may influence the dynamics of blood flow and valve function. These insights into the hemodynamic changes induced by calcification contribute to a better understanding of the progression of aortic valve diseases and could inform more effective diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

Restenosis typically occurs in regions of low and oscillating wall shear stress, which also favor the accumulation of atherogenic macromolecules such as low‐density lipoprotein (LDL). This study aims to evaluate LDL transport and accumulation at the carotid artery bifurcation following carotid artery stenting (CAS) by means of computational simulation. The computational model consists of coupled blood flow and LDL transport, with the latter being modeled as a dilute substance dissolved in the blood and transported by the flow through a convection‐diffusion transport equation. The endothelial layer was assumed to be permeable to LDL, and the hydraulic conductivity of LDL was shear‐dependent. Anatomically realistic geometric models of the carotid bifurcation were built based on pre‐ and post‐stent computed tomography (CT) scans. The influence of stent design was investigated by virtually deploying two different types of stents (open‐ and closed‐cell stents) into the same carotid bifurcation model. Predicted LDL concentrations were compared between the post‐stent carotid models and the relatively normal contralateral model reconstructed from patient‐specific CT images. Our results show elevated LDL concentration in the distal section of the stent in all post‐stent models, where LDL concentration is 20 times higher than that in the contralateral carotid. Compared with the open‐cell stents, the closed‐cell stents have larger areas exposed to high LDL concentration, suggesting an increased risk of stent restenosis. This computational approach is readily applicable to multiple patient studies and, once fully validated against follow‐up data, it can help elucidate the role of stent strut design in the development of in‐stent restenosis after CAS. [ABSTRACT FROM AUTHOR]

One of significant impact of stent usage for the treatment of the saccular aneurysm is deformation of the parent vessel. Present study demonstrates the influence of the aneurysm deformation caused by the stent on the risk of aneurysm rupture. Computational fluid dynamic is applied for the modeling of the blood flow inside three internal carotid artery (ICA) aneurysms with different neck angles. One-way fluid–structure interaction model is applied for the interaction of the blood and vessel. Two stage of deformation is applied on the parent vessel to analyze the influence of deformation on the hemodynamic factors of wall shear stress and oscillatory shear index. Achieved results indicate that the deformation of the aneurysm by the stent significantly reduce wall shear stress is on the sac wall and decrease the risk of internal carotid artery ICA aneurysm rupture. Our finding confirm that the main effect of aneurysm deformation is reduction of the blood velocity near ostium region. [ABSTRACT FROM AUTHOR]

The stenosis and non-Newtonian property of the uid in the blood ow represent the behavior of Herschel-Buckley uid. In a tapered tube model all the vessels which carry blood towards the tissues are considered as long, slowly tapering cones rather than cylinders. Since the blood ow consist of two regions in which one is central region, consist of concentrated blood cells and its behavior is non-Newtonian and other region is peripheral layer of plasma which represent the Newtonian behavior of uid motion. In present paper, we have considered the ow of blood through a uniform tapered tube which obeys the Bingham uid model and obtained the condition for the wall shear stress and pressure gradient. Further in various graphs we represent the variation of shear stress at the wall and pressure gradient with respect to suspension concentration and tapered angle over the ow rate range 0.01 to 0.1 cc/sec. [ABSTRACT FROM AUTHOR]

In this study, the role of sac section area and parent vessel diameter on the hemodynamic feature of the blood flow in selected internal carotid artery (ICA) aneurysms is comprehensively investigated. The changes of wall shear stress, pressure, and oscillatory shear index (OSI) of blood stream on the vessel for various aneurysms with coiling treatment. To attain hemodynamic factors, computational technique is used for the modeling of non-Newtonian transient blood flow inside the three different ICA aneurysms. Three different saccular models with various Parent vessel mean Diameter is investigated in this study. The achieved outcomes show that increasing the diameter of the parent vessel directly decreases the OSI value on the sac surface. In addition, the mean wall shear stress decreases with the increase of the parent vessel diameter. [ABSTRACT FROM AUTHOR]

The wall shear stress (WSS) exerted by blood flowing through microvascular capillaries is an established driver of new blood vessel growth, or angiogenesis. Such adaptations are central to many physiological processes in both health and disease, yet three-dimensional (3D) WSS characteristics in real angiogenic microvascular networks are largely unknown. This marks a major knowledge gap because angiogenesis, naturally, is a 3D process. To advance current understanding, we model 3D red blood cells (RBCs) flowing through rat angiogenic microvascular networks using state-of-the-art simulation. The high-resolution fluid dynamics reveal 3D WSS patterns occurring at sub-endothelial cell (EC) scales that derive from distinct angiogenic morphologies, including microvascular loops and vessel tortuosity. We identify the existence of WSS hot and cold spots caused by angiogenic surface shapes and RBCs, and notably enhancement of low WSS regions by RBCs. Spatiotemporal characteristics further reveal how fluctuations follow timescales of RBC "footprints." Altogether, this work provides a new conceptual framework for understanding how shear stress might regulate EC dynamics in vivo. Graphical Abstract [ABSTRACT FROM AUTHOR]

We present a microfluidic cell culture platform for studying the responses of Endothelial Cells (ECs) under pulsatile flow conditions of blood plasma. Through numerical investigations, we explore the dynamic behaviors of the Endothelial Cell Monolayer under both physiological and extreme conditions, including the formation of recirculation zones. Furthermore, we conduct a quantitative analysis of the Wall Shear Stress (WSS) magnitude on the EC surface and evaluate the Oscillatory Shear Index (OSI) to gain insights into the extent of WSS reversal within a single cycle across different spatial locations. Our findings reveal that the ECs deform in the direction of the flow, periodically returning to their initial position, with slight vertical deformation in the nanometer scale. In contrast to our previous observations for startup rheometry, cell membrane thinning is found to be more prominent at the lateral points of the cell protrusion, where fluid detachment from the cell surface initiates, rather than at the top. We further note that negative shear stresses emerge within the cytoplasm. Moreover, the shear stresses within the nucleus remain consistent for both rheometric protocols, while the normal stresses are slightly lower during pulsatile experiments. Finally, the model provides insight into the actual phenomena that arise in vivo as well as the expected behaviors in the vicinity of the endothelium of a vessel. [ABSTRACT FROM AUTHOR]

Several methods have been developed for generating 3D, in vitro, organ-on-chip models of human vasculature to study vascular function, transport, and tissue engineering. However, many of these existing models lack the hierarchical nature of the arterial-to-capillary-to-venous architecture that is key to capturing a more comprehensive view of the human microvasculature. Here, we present a perfusable, multi-compartmental model that recapitulates the three microvascular compartments to assess various physiological properties such as vessel permeability, vasoconstriction dynamics, and circulating cell arrest and extravasation. Viscous finger patterning and passive pumping create the larger arterial and venular lumens, while the smaller diameter capillary bed vessels are generated through self-assembly. These compartments anastomose and form a perfusable, hierarchical system that portrays the directionality of blood flow through the microvasculature. The addition of collagen channels reduces the apparent permeability of the central capillary region, likely by reducing leakage from the side channels, enabling more accurate measurements of vascular permeability—an important motivation for this study. Furthermore, the model permits modulation of fluid flow and shear stress conditions throughout the system by using hydrostatic pressure heads to apply pressure differentials across either the arteriole or the capillary. This is a pertinent system for modeling circulating tumor or T cell dissemination and extravasation. Circulating cells were found to arrest in areas conducive to physical trapping or areas with the least amount of shear stress, consistent with hemodynamic or mechanical theories of metastasis. Overall, this model captures more features of human microvascular beds and is capable of testing a broad variety of hypotheses. [ABSTRACT FROM AUTHOR]

The present study analyzes the theoretical consequences of slip effects in a complex stenosed region. The flow of blood in a stenosed region is incorporated with hybrid nanofluid features which are being prepared with copper and copper oxide nanoparticles. The flow is also intensified by applying an electric field in the axial direction. The governing equations for the proposed paradigm are solved and the corresponding closed-form solutions are obtained for the cases of mild stenosis. Parameters such as Electro-osmotic, velocity slip and Helmholtz–Smoluchowski are specially focused in this study. The heat transfer, hemodynamic velocity, wall shear stress and resistance impedance for the flow are precisely determined. The various parameters that influence the physical characteristics of flow are plotted, and their effects are discussed in detail. The present model has the potential application in medical pumps for drug delivery systems. [ABSTRACT FROM AUTHOR]

Spatial patterns of elevated wall shear stress and pressure due to blood flow past aortic stenosis (AS) are studied using GPU-accelerated patient-specific computational fluid dynamics. Three cases of moderate to severe AS, one with a dilated ascending aorta and two within the normal range (root diameter less than 4cm) are simulated for physiological waveforms obtained from echocardiography. The computational framework is built based on sharp-interface Immersed Boundary Method, where aortic geometries segmented from CT angiograms are integrated into a high-order incompressible Navier–Stokes solver. The key question addressed here is, given the presence of turbulence due to AS which increases wall shear stress (WSS) levels, why some AS patients undergo much less aortic dilation. Recent case studies of AS have linked the existence of an elevated WSS hotspot (due to impingement of AS on the aortic wall) to the dilation process. Herein we further investigate the WSS distribution for cases with and without dilation to understand the possible hemodynamics which may impact the dilation process. We show that the spatial distribution of elevated WSS is significantly more focused for the case with dilation than those without dilation. We further show that this focal area accommodates a persistent pocket of high pressure, which may have contributed to the dilation process through an increased wall-normal forcing. The cases without dilation, on the contrary, showed a rather oscillatory pressure behaviour, with no persistent pressure "buildup" effect. We further argue that a more proximal branching of the aortic arch could explain the lack of a focal area of elevated WSS and pressure, because it interferes with the impingement process due to fluid suction effects. These phenomena are further illustrated using an idealized aortic geometry. We finally show that a restored inflow eliminates the focal area of elevated WSS and pressure zone from the ascending aorta. Author summary: Dilation of the aorta can be a precursor to fatal events such as aortic dissection. Aortic dilation is an involved process which depends on the biological properties of the aorta as well as on the aortic blood flow features. Recent flow imaging studies suggest that a stenotic (i.e., narrowed) aortic valve leads to a turbulent flow character which elevates the fluid stresses applied onto the aortic wall. These excessive stresses are then linked to dilation of the aorta through weakening of the vessel wall tissue. Not all patients with stenotic aortic valves develop aortic dilation, however. Aortic geometry may be a key factor in whether or not a stenotic valve leads to dilation, as it affects the way the restricted aortic flow jet interacts with the vessel wall. We investigate the role of this factor by studying three aortic stenosis patients with and without aortic dilation. To this end, we set up and use a high-fidelity image-based computational framework for detailed simulation of the turbulent flow states and show that certain geometrical layouts of the aorta may be more likely to lead to dilation, because they create persisting and focused areas of excessive blood flow stress on the aortic wall. [ABSTRACT FROM AUTHOR]

Central venous disease (CVD) with stenosis or occlusion is a severe and prevalent complication for chronic hemodialysis (HD) patients, resulting in dialysis access dysfunction. Percutaneous transluminal angioplasty with stent placement (PTS) has become one of the first‐line treatments for CVD. In clinical practice, the extra stents would be used if the curative efficacy of a single stent were unsatisfactory. Aiming to evaluate the therapeutic effect of different PTS schemes, computational fluid dynamics (CFD) simulations on four patients were performed to compare the hemodynamic characteristics of real‐life HD patients after stent placement. The three‐dimensional central vein's models of each patient were built using computational tomography angiography (CTA) images, and idealized models were constructed as contrast. Two inlet velocity modes were imposed to imitate the blood flow rate of healthy and HD patients. The hemodynamic parameters for different patients were investigated, including wall shear stress (WSS), velocity, and helicity. The results showed that the implantation of double stents is able to improve flexibility. When subjected to external force, the double stents have better radial stiffness. This paper evaluated the therapeutic efficacy of stent placement and provided a theoretical basis for CVD intervention in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Arterial deformations arise in blood flow when surrounding tissue invades the space available for a blood vessel to maintain its circular cross section, the most immediate effects being a reduction in blood flow and redistribution of shear stress. Here we consider deformations from circular to elliptic cross sections. Solution of this problem in steady flow is fairly straightforward. The focus in the present paper is on pulsatile flow where the change from circular to elliptic cross sections is associated with a transition in the character of the equations governing the flow from Bessel to Mathieu equations. The main aim of our study is to examine the hemodynamic consequences of the change from circular to elliptic cross sections and on possible implications of this change in blood flow regulation. The study of this problem has been hampered in the past because of difficulties involved in the solution of the governing equations. In the present study we describe methods we have used to overcome some of these difficulties and present a comprehensive set of results based on these methods. In particular, vessel deformation is examined under two different conditions relevant to blood flow regulation: (i) keeping cross sectional area constant and (ii) keeping cross sectional circumference constant. The results provide an important context for the mechanism of neurovascular control of blood flow under the pathological conditions of vessel deformation. The difficulty which has characterized this problem is that it involves elements of mathematics which are well outside the scope of a clinical/physiological study, while it actually involves clinical/physiological elements which are well outside the scope of a mathematical study. We hope that the context which we provide in this paper helps resolve this difficulty. [ABSTRACT FROM AUTHOR]

The ability of endothelial cells to respond to blood flow is fundamental for the correct formation and maintenance of a functional and hierarchically organized vascular network. Defective flow responses, in particular related to high flow conditions, have been associated with atherosclerosis, stroke, arteriovenous malformations, and neurodegenerative diseases. Yet, the molecular mechanisms involved in high flow response are still poorly understood. Here, we described the development and validation of a 96-wells fluidic system, with interchangeable cell culture and fluidics, to perform high-throughput screenings under laminar high-flow conditions. We demonstrated that endothelial cells in our newly developed 96-wells fluidic system respond to fluid flow-induced shear stress by aligning along the flow direction and increasing the levels of KLF2 and KLF4. We further demonstrate that our 96-wells fluidic system allows for efficient gene knock-down compatible with automated liquid handling for high-throughput screening platforms. Overall, we propose that this modular 96-well fluidic system is an excellent platform to perform genome-wide and/or drug screenings to identify the molecular mechanisms involved in the responses of endothelial cells to high wall shear stress. [ABSTRACT FROM AUTHOR]

Stroke occur mainly due to arterial thrombosis and rupture of cerebral blood vessels. Previous studies showed that blood flow-induced wall shear stress is an essential bio marker for estimating atherogenesis. It is a common practice to use computational fluid dynamics (CFD) simulations to calculate wall shear stress and to quantify blood flow. Reliability of predicted CFD results greatly depends on the accuracy of applied boundary conditions. Previously, the boundary conditions were estimated by varying values so that they matched the clinical data. It is applicable upon the availability of clinical data. Meanwhile, in most cases all that can be accessed are arterial geometry and inflow rate. Consequently, there is a need to devise a tool to estimate boundary values such as resistance and compliance of arteries. This study proposes an analytical framework to estimate the boundary conditions for a carotid artery based on the geometries of the downstream arteries available from clinical images. [ABSTRACT FROM AUTHOR]

It is crucial for hemostasis that platelets are rapidly recruited to the site of vascular injury by the adhesive ligand von Willebrand factor (VWF) multimers. The metalloproteinase ADAMTS13 regulates this hemostatic activity by proteolytically reducing the size of VWF and its proteolytic kinetics has been investigated by biochemical and single-molecule biophysical methods. However, how ADAMTS13 cleaves VWF in flowing blood remains poorly defined. To investigate the force-induced VWF cleavage, VWF A1A2A3 tridomains were immobilized and subjected to hydrodynamic forces in the presence of ADAMTS13. We demonstrated that the cleavage of VWF A1A2A3 by ADAMTS13 exhibited biphasic kinetics governed by shear stress, but not shear rate. By fitting data to the single-molecule Michaelis-Menten equation, the proteolytic constant k cat of ADAMTS13 had two distinct states. The mean proteolytic constant of the fast state (k cat-fast) was 0.005 ± 0.001 s−1, which is >10-fold faster than the slow state (k cat-slow = 0.0005 ± 0.0001 s−1). Furthermore, proteolytic constants of both states were regulated by shear stress in a biphasic manner, independent of the solution viscosity, indicating that the proteolytic activity of ADAMTS13 was regulated by hydrodynamic force. The findings provide new insights into the mechanism underlying ADAMTS13 cleaving VWF under flowing blood. • The cleavage of VWF A1A2A3 by ADAMTS13 exhibits a biphasic manner under flow. • ADAMTS13 cleaving VWF A1A2A3 showed fast and slow proteolytic states. • Both states were biphasically regulated by shear stress, implying an optimal configuration of unfolded A2 for cleavage. [ABSTRACT FROM AUTHOR]

In vitro investigations demonstrate that human erythrocytes synthesize nitric oxide via a functional isoform of endothelial nitric oxide synthase (NOS) (RBC-NOS). We tested the hypothesis that phosphorylation of RBC-NOS at serine residue 1177 (RBC-NOS1177) would be amplified in blood draining-active skeletal muscle. Furthermore, given hypoxemia modulates local blood flow and thus shear stress, and nitric oxide availability, we performed duplicate experiments under normoxia and hypoxia. Nine healthy volunteers performed rhythmic handgrip exercise at 60% of individualized maximal workload for 3.5 min while breathing room air (normoxia) and after being titrated to an arterial oxygen saturation ≈80% (hypoxemia). We measured brachial artery blood flow by high-resolution duplex ultrasound, while continuously monitoring vascular conductance and mean arterial pressure using finger photoplethysmography. Blood was sampled during the final 30 s of each stage from an indwelling cannula. Blood viscosity was measured to facilitate calculation of accurate shear stresses. Erythrocytes were assessed for levels of phosphorylated RBC-NOS1177 and cellular deformability from blood collected at rest and during exercise. Forearm exercise increased blood flow, vascular conductance, and vascular shear stress, which coincided with a 2.7 ± 0.6-fold increase in RBC-NOS1177 phosphorylation (P < 0.0001) and increased cellular deformability (P < 0.0001) under normoxia. When compared with normoxia, hypoxemia elevated vascular conductance and shear stress (P < 0.05) at rest, while cellular deformability (P < 0.01) and RBC-NOS1177 phosphorylation (P < 0.01) increased. Hypoxemic exercise elicited further increases in vascular conductance, shear stress, and cell deformability (P < 0.0001), although a subject-specific response in RBC-NOS1177 phosphorylation was observed. Our data yield novel insights into the manner that hemodynamic force and oxygen tension modulate RBC-NOS in vivo. [ABSTRACT FROM AUTHOR]

Vascular endothelial polarity induced by blood flow plays crucial roles in the development of atherosclerosis. Loss of endothelial polarity leads to an increase in permeability and leukocyte recruitment, which are crucial hallmarks of atherosclerotic initiation. Endothelial cells exhibit a morphological adaptation to hemodynamic shear stress and possesses planar cell polarity to the direction of blood flow. However, the mechanism of how hemodynamic shear stress regulates endothelial planar cell polarity has not been firmly established. Here, we found that TET1s, a short isoform of Tet methylcytosine dioxygenase 1, was a mediator in the regulation of the planar cell polarity in endothelial cells in response to hemodynamic shear stress. In the process, low expression of TET1s induced by oscillatory shear stress led to the endothelial planar polarity damage through inhibition of F-actin polymerization. TET1s can regulate demethylation level of the sFRP-1 promoter to alter the expression of sFRP-1, which affects the interaction of sFRP-1/Fzd4 and F-actin polymerization. Our study revealed the mechanism of how TET1s mediates endothelial planar cell polarity in response to hemodynamic shear stress and provides a new insight for the prevention of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Hemostatic dysfunction during extracorporeal membrane oxygenation (ECMO) due to blood-circuit interaction and the consequences of shear stress imposed by flow rates lead to rapid coagulation cascade and thrombus formation in the ECMO system and blood vessels. We aimed to identify the incidence and risk factors for cannula-associated arterial thrombosis (CaAT) post-decannulation. Methods: A retrospective study of patients undergoing arterial cannula removal following ECMO was performed. We evaluated the incidence of CaAT and compared the characteristics, ECMO machine parameters, cannula sizes, number of blood products transfused during ECMO, and daily hemostasis parameters in patients with and without CaAT. Multivariate analysis identified the risk factors for CaAT. Results: Forty-seven patients requiring venoarterial ECMO (VA-ECMO) or hybrid methods were recruited for thrombosis screening. The median Sequential Organ Failure Assessment score was 11 (interquartile range, 8–13). CaAT occurred in 29 patients (61.7%), with thrombosis in the superficial femoral artery accounting for 51.7% of cases. The rate of limb ischemia complications in the CaAT group was 17.2%. Multivariate analysis determined that the ECMO flow rate–body surface area (BSA) ratio (100 ml/min/m²) was an independent factor for CaAT, with an odds ratio of 0.79 (95% confidence interval, 0.66–0.95; P=0.014). Conclusions: We found that the incidence of CaAT was 61.7% following successful decannulation from VA-ECMO or hybrid modes, and the ECMO flow rate–BSA ratio was an independent risk factor for CaAT. We suggest screening for arterial thrombosis following VA-ECMO, and further research is needed to determine the risks and benefits of such screening. [ABSTRACT FROM AUTHOR]

Blood image intensity has been used to detect erythrocyte sedimentation rate (ESR). However, it does not give information on the biophysical properties of blood samples under continuous ESR. In this study, to quantify mechanical variations of blood under continuous ESR, blood shear stress and blood image intensity were obtained by analyzing blood flows in the capillary channel. A blood sample is loaded into a driving syringe to demonstrate the proposed method. The blood flow rate is set in a periodic on–off pattern. A blood sample is then supplied into a capillary chip, and microscopic blood images are captured at specific intervals. Blood shear stress is quantified from the interface of the bloodstream in the coflowing channel. τ0 is defined as the maximum shear stress obtained at the first period. Simultaneously, ESRτ is then obtained by analyzing temporal variations of blood shear stress for every on period. AII is evaluated by analyzing the temporal variation of blood image intensity for every off period. According to the experimental results, a shorter period of T = 4 min and no air cavity contributes to the high sensitivity of the two indices (ESRτ and AII). The τ0 exhibits substantial differences with respect to hematocrits (i.e., 30–50%) as well as diluents. The ESRτ and AII showed a reciprocal relationship with each other. Three suggested properties represented substantial differences for suspended blood samples (i.e., hardened red blood cells, different concentrations of dextran solution, and fibrinogen). In conclusion, the present method can detect variations in blood samples under continuous ESR effectively. [ABSTRACT FROM AUTHOR]

In the present paper, we investigate how the reductions in shear stresses and pressure losses in microfluidic gaps are directly linked to the local characteristics of cell-free layers (CFLs) at channel Reynolds numbers relevant to ventricular assist device (VAD) applications. For this, detailed studies of local particle distributions of a particulate blood analog fluid are combined with wall shear stress and pressure loss measurements in two complementary set-ups with identical flow geometry, bulk Reynolds numbers and particle Reynolds numbers. For all investigated particle volume fractions of up to 5 % , reductions in the stress and pressure loss were measured in comparison to a flow of an equivalent homogeneous fluid (without particles). We could explain this due to the formation of a CFL ranging from 10 to 20 μ m. Variations in the channel Reynolds number between Re = 50 and 150 did not lead to measurable changes in CFL heights or stress reductions for all investigated particle volume fractions. These measurements were used to describe the complete chain of how CFL formation leads to a stress reduction, which reduces the apparent viscosity of the suspension and results in the Fåhræus–Lindqvist effect. This chain of causes was investigated for the first time for flows with high Reynolds numbers ( R e ∼ 100 ), representing a flow regime which can be found in the narrow gaps of a VAD. [ABSTRACT FROM AUTHOR]