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The rotor axial displacement of the full magnetic levitation blood pump varies with the operating conditions. The effect of rotor axial displacement on simulation results is unclear. This study aimed to evaluate the effect of rotor axial displacement on the predicted blood pump flow field, hydraulic performance, and hemocompatibility through simulation. This study used the CentriMag blood pump as a model, and conducted computational fluid dynamics simulations to assess the impact of rotor displacement. Considering rotor axial displacement leads to opposite results regarding predicted residence time and thrombotic risk compared with not considering rotor axial displacement. Not considering rotor axial displacement leads to deviations in the predicted values, where the effects on the flow field within the blood pump, ratio of secondary flow, and amount of shear stress >150 Pa are significant. The variation in the back clearance of the blood pump caused by the ideal and actual rotor displacements is the main cause of the above phenomena. Given that the rotor axial displacement significantly impacts the simulation accuracy, the effect of rotor axial displacement must be considered in the simulation., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Systematic research into device-induced red blood cell (RBC) damage beyond hemolysis, including correlations between hemolysis and RBC-derived extracellular vesicles, remains limited. This study investigated non-physiological shear stress-induced RBC damage and changes in related biochemical indicators under two blood pump clinical support conditions. Pressure heads of 100 and 350 mmHg, numerical simulation methods, and two in vitro loops were utilized to analyze the shear stress and changes in RBC morphology, hemolysis, biochemistry, metabolism, and oxidative stress. The blood pump created higher shear stress in the 350-mmHg condition than in the 100-mmHg condition. With prolonged blood pump operation, plasma-free hemoglobin and cholesterol increased, whereas plasma glucose and nitric oxide decreased in both loops. Notably, plasma iron and triglyceride concentrations increased only in the 350-mmHg condition. The RBC count and morphology, plasma lactic dehydrogenase, and oxidative stress across loops did not differ significantly. Plasma extracellular vesicles, including RBC-derived microparticles, increased significantly at 600 min in both loops. Hemolysis correlated with plasma triglyceride, cholesterol, glucose, and nitric oxide levels. Shear stress, but not oxidative stress, was the main cause of RBC damage. Hemolysis alone inadequately reflects overall blood pump-induced RBC damage, suggesting the need for additional biomarkers for comprehensive assessments., (© 2024. International Federation for Medical and Biological Engineering.)

Purpose: This study aimed to investigate the effects of lower-extremity cannulation on the intra-arterial hemodynamic environment, oxygen content, blood damage, and thrombosis risk under different levels of veno-arterial (V-A) ECMO support., Methods: Computational fluid dynamics methods were used to investigate the effects of different levels of ECMO support (ECMO flow ratios supplying oxygen-rich blood 100-40 %). Flow rates and oxygen content in each arterial branch were used to determine organ perfusion. A new thrombosis model considering platelet activation and deposition was proposed to determine the platelet activation and thrombosis risk at different levels of ECMO support. A red blood cell damage model was used to explore the risk of hemolysis., Results: Our study found that partial recovery of cardiac function improved the intra-arterial hemodynamic environment, with reduced impingement of the intra-arterial flow field by high-velocity blood flow from the cannula, a flow rate per unit time into each arterial branch closer to physiological levels, and improved perfusion in the lower extremities. Partial recovery of cardiac function helps reduce intra-arterial high shear stress and residence time, thereby reducing blood damage. The overall level of hemolysis and platelet activation in the aorta decreased with the gradual recovery of cardiac contraction function. The areas at high risk of thrombosis under V-A ECMO femoral cannulation support were the aortic root and the area distal to the cannula, which moved to the descending aorta when cardiac function recovered to 40-60 %. However, with the recovery of cardiac contraction function, hypoxic blood pumped by the heart is insufficient in supplying oxygen to the front of the aortic arch, which may result in upper extremity hypoxia., Conclusion: We developed a thrombosis risk prediction model applicable to ECMO cannulation and validated the model accuracy using clinical data. Partial recovery of cardiac function contributed to an improvement in the aortic hemodynamic environment and a reduction in the risk of blood damage; however, there is a potential risk of insufficient perfusion of oxygen-rich blood to organs., Competing Interests: Declaration of competing interest There is no conflict of interest in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To investigate the effects of blood pumps operated in different modes on nonphysiologic flow patterns, cell and protein function, and the risk of bleeding, thrombosis, and hemolysis, an extracorporeal blood pump (CentriMag) was operated in three clinical modalities including heart failure (HF), venous-venous (V-V) extracorporeal membrane oxygenation (ECMO), and venous-arterial (V-A) ECMO. Computational fluid dynamics (CFD) methods and coupled hemolysis models as well as recently developed bleeding and thrombosis models associated with changes in platelet and von Willebrand factor (vWF) function were used to predict hydraulic performance and hemocompatibility. The V-A ECMO mode had the highest flow losses and shear stress levels, the V-V ECMO mode was intermediate, and the HF mode was the lowest. Different nonphysiologic flow patterns altered cell/protein morphology and function. The V-A ECMO mode resulted in the highest levels of platelet activation, receptor shedding, vWF unfolding, and high molecular weight multimers vWF (HMWM-vWF) degradation, leading to the lowest platelet adhesion and the highest vWF binding capacity, intermediate in the V-V ECMO mode, and opposite in the HF mode. The V-A ECMO mode resulted in the highest risk of bleeding, thrombosis, and hemolysis, with the V-V ECMO mode intermediate and the HF mode lowest. These findings are supported by published experimental or clinical statistics. Further studies found that secondary blood flow passages resulted in the highest risk of blood damage. Nonphysiologic blood flow patterns were strongly associated with cell and protein function changing, blood damage, and complications., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Clinical Impact: Studies have shown that the biomechanical indicators based on multi-scale models are more effective in accurately assessing the rupture risk of AAA. To meet the need for clinical monitoring and rapid decision making, the typical morphological parameters associated with AAA rupture and their relationships with the mechanical environment have been summarized, which provide a reference for clinical preoperative risk assessment of AAA., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Gastrojejunostomy is a prominent approach in managing distal gastric cancer that is unresectable due to gastric outlet obstruction (GOO). Research has demonstrated that stomach-partitioning gastrojejunostomy (SPGJ) exhibits superior clinical efficacy compared to conventional gastrojejunostomy (CGJ), however, the underlying mechanism of this phenomenon remains elusive. This study constructed 3D models of the SPGJ and CGJ based on the computed tomography (CT) images obtained from a patient diagnosed with distal gastric cancer. The biomechanical patterns of these procedures in the digestive system were subsequently compared through numerical simulations and in vitro experiments. The results of the numerical simulation demonstrated that the model following SPGJ promoted the discharge of food through the anastomotic orifice and into the lower jejunum. Furthermore, a decrease in passage size after partitioning, the low-level velocity of esophageal, and an increase in contents viscosity effectively inhibited the flow through the passage to the pylorus, ultimately reducing stimulation to tumor. The study also revealed that favorable gastric emptying is associated with a smaller passage and faster inlet velocity, and that lower contents viscosity. ​The experimental findings conducted in vitro demonstrated that SPGJ exhibited superior efficacy in obstructing the flow near the pylorus in comparison to CGJ. Moreover, a decrease in passage size correlates with a reduction in fluid flow towards the pylorus. These results provide the foundation of theory and practice for the surgical management of patients with GOO resulting from unresectable distal gastric cancer, and have potential implications for clinical interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Women with abdominal aortic aneurysm (AAA) have a higher incidence of complications after Endovascular aneurysm repair (EVAR), most of which are related to the migration of stent-graft. The different force acting on the stent-graft after EVAR caused by different abdominal artery anatomy of male and female AAA patients may be the reason for the sex-different complications. This article aims to explore the possible biomechanical mechanisms of sex differences by making a comparison of displacement force acting on the stent graft of male and female AAA patients. To explore the effect of different vascular anatomy on stent-graft migration, the uniformed models were constructed according to the specific vascular anatomy parameters of AAA patients of different sex, which have been measured before. The computational fluid dynamics method was used to quantitate the pulsatile force acting on the stent-graft after EVAR in a cardiac cycle. Then the displacement force was calculated with the pressure and the wall shear stress, and the total and area-weighted average of displacement force acting on the stent-graft were compared respectively. In one cardiac cycle, the wall pressure for the male model is greater than that of the female model (2.7-4.4 vs. 2.2-3.4 N), and the wall shear force for the female model is slightly greater (0-0.0065 vs. 0-0.0055 N). The displacement force is mainly provided by the wall pressure, which is also greater in the male model. However, the area-averaged displacement force is greater for the female model than that for the male model (180-290 vs. 160-250 Pa). Because of the different vascular anatomies, the impact caused by the pulsating aortic blood flow on the AAA stent-graft of women after EVAR was greater than that of men. Women's vascular anatomy leads to greater area-averaged displacement force after stent-graft implantation, resulting in a greater risk of stent-graft migration, which might be one of the reasons why women had a higher incidence of complications after EVAR., (© 2023 John Wiley & Sons Ltd.)

Purpose: To develop a mathematical model for predicting shear-induced von Willebrand factor (vWF) function modification which can be used to guide ventricular assist devices (VADs) design, and evaluate the damage of high molecular weight multimers (HMWM)-vWF in VAD patients for reducing clinical complications., Methods: Mathematical models were constructed based on three morphological variations (globular vWF, unfolded vWF and degraded vWF) of vWF under shear stress conditions, in which parameters were obtained from previous studies or fitted by experimental data. Different clinical support modes (pediatric vs. adult mode), different VAD operating states (pulsation vs. constant mode) and different clinical VADs (HeartMate II, HeartWare and CentriMag) were utilized to analyze shear-induced damage of HMWM-vWF based on our vWF model. The accuracy and feasibility of the models were evaluated using various experimental and clinical cases, and the biomechanical mechanisms of HMWM-vWF degradation induced by VADs were further explained., Results: The mathematical model developed in this study predicted VAD-induced HMWM-vWF degradation with high accuracy (correlation with experimental data r 2  > 0.99). The numerical results showed that VAD in the pediatric mode resulted in more HMWM-vWF degradation per unit time and per unit flow rate than in the adult mode. However, the total degradation of HMWM-vWF is less in the pediatric mode than in the adult mode because the pediatric mode has fewer times of blood circulation than the adult mode in the same amount of time. The ratio of HMWM-vWF degradation was lower in the pulsation mode than in the constant mode. This is due to the increased flushing of VADs in the pulsation mode, which avoids prolonged stagnation of blood in high shear regions. This study also found that the design feature, rotor size and volume of the VADs, and the superimposed regions of high shear stress and long residence time inside VADs affect the degradation of HMWM-vWF. The axial flow VADs (HeartMate II) showed higher degradation of HMWM-vWF compared to centrifugal VADs (HeartWare and CentriMag). Compared to fully magnetically suspended VADs (CentriMag), hydrodynamic suspended VADs (HeartWare) produced extremely high degradation of HWMW-vWF in its narrow hydrodynamic clearance. Finally, the study used a mathematical model of HMWM-vWF degradation to interpret the clinical statistics from a biomechanical perspective and found that minimizing the rotating speed of VADs within reasonable limits helps to reduce HWMW-vWF degradation. All predicted conclusions are supported by the experimental and clinical data., Conclusion: This study provides a validated mathematical model to assess the shear-induced degradation of HMWM-vWF, which can help to evaluate the damage of HMWM-vWF in patients implanted with VADs for reducing clinical complications, and to guide the optimization of VADs for improving hemocompatibility., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Aims: Atherosclerosis preferentially occurs at regions in arterial branching, curvature, and stenosis, which may be explained by the geometric predilection of low-density lipoprotein (LDL) concentration polarization that has been investigated in major arteries in previous studies. Whether this also happens in arterioles remains unknown., Methods: Herein, a radially non-uniform distribution of LDL particles and a heterogeneous endothelial glycocalyx layer in the mouse ear arterioles, as shown by fluorescein isothiocyanate labeled wheat germ agglutinin (WGA-FITC), were successfully observed by a non-invasive two-photon laser-scanning microscopy (TPLSM) technique. The stagnant film theory was applied as the fitting function to evaluate LDL concentration polarization in arterioles., Results: The concentration polarization rate (CPR, the ratio of the number of polarized cases to that of total cases) in the inner walls of curved and branched arterioles was 22% and 31% higher than the outer counterparts, respectively. Results from the binary logistic regression and multiple linear regression analysis showed that endothelial glycocalyx thickness increases CPR and the thickness of the concentration polarization layer (CPL). Flow field computation indicates no obvious disturbances or vortex in modeled arterioles with different geometries and the mean wall shear stress is about 7.7-9.0 Pa., Conclusions: These findings suggest a geometric predilection of LDL concentration polarization in arterioles for the first time, and the existence of an endothelial glycocalyx, acting together with a relatively high wall shear stress in arterioles, may explain to some extent why atherosclerosis rarely occurs in these regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: The geometric structure of the membrane oxygenator can exert an impact on its hemodynamic features, which contribute to the development of thrombosis, thereby affecting the clinical efficacy of ECMO treatment. The purpose of this study is to investigate the impact of varying geometric structures on hemodynamic features and thrombosis risk of membrane oxygenators with different designs., Methods: Five oxygenator models with different structures, including different number and location of blood inlet and outlet, as well as variations in blood flow path, were established for investigation. These models are referred to as Model 1 (Quadrox-i Adult Oxygenator), Model 2 (HLS Module Advanced 7.0 Oxygenator), Model 3 (Nautilus ECMO Oxygenator), Model 4 (OxiaACF Oxygenator) and Model 5 (New design oxygenator). The hemodynamic features of these models were numerically analyzed using the Euler method combined with computational fluid dynamics (CFD). The accumulated residence time (ART) and coagulation factor concentrations (C[i], where i represents different coagulation factors) were calculated by solving the convection diffusion equation. The resulting relationships between these factors and the development of thrombosis in the oxygenator were then investigated., Results: Our results show that the geometric structure of the membrane oxygenator, including the location of the blood inlet and outlet as well as the design of the flow path, has a significant impact on the hemodynamic surroundings within the oxygenator. In comparison to Model 4, which had the inlet and outlet located in the center position, Model 1 and Model 3, which had the inlet and outlet at the edge of the blood flow field, exhibited a more uneven distribution of blood flow within the oxygenator, particularly in areas distant from the inlet and outlet, which was accompanied with lower flow velocity and higher values of ART and C[i], leading to the formation of flow dead zones and an elevated risk of thrombosis. The oxygenator of Model 5 is designed with a structure that features multiple inlets and outlets, which greatly improves the hemodynamic environment inside the oxygenator. This results in a more even distribution of blood flow within the oxygenator, reducing areas with high values of ART and C[i], and ultimately lowering the risk of thrombosis. The oxygenator of Model 3 with circular flow path section shows better hemodynamic performance compared to the oxygenator of Model 1 with square circular flow path. The overall ranking of hemodynamic performance for all five oxygenators is as follows: Model 5 > Model 4 > Model 2 > Model 3 > Model 1, indicating that Model 1 has the highest thrombosis risk while Model 5 has the lowest., Conclusion: The study reveals that the different structures can affect the hemodynamic characteristics inside membrane oxygenators. The design of multiple inlets and outlets can improve the hemodynamic performance and reduce the thrombosis risk in membrane oxygenators. These findings of this study can be used to guide the optimization design of membrane oxygenators for improving hemodynamic surroundings and reducing thrombosis risk., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cardiovascular disease is the leading cause of death worldwide, accounting for 48.0% of all deaths in Europe and 34.3% in the United States. Studies have shown that arterial stiffness takes precedence over vascular structural changes and is therefore considered to be an independent predictor of many cardiovascular diseases. At the same time, the characteristics of Korotkoff signal is related to vascular compliance. The purpose of this study is to explore the feasibility of detecting vascular stiffness based on the characteristics of Korotkoff signal. First, the Korotkoff signals of normal and stiff vessels were collected and preprocessed. Then the scattering features of Korotkoff signal were extracted by wavelet scattering network. Next, the long short-term memory (LSTM) network was established as a classification model to classify the normal and stiff vessels according to the scattering features. Finally, the performance of the classification model was evaluated by some parameters, such as accuracy, sensitivity, and specificity. In this study, 97 cases of Korotkoff signal were collected, including 47 cases from normal vessels and 50 cases from stiff vessels, which were divided into training set and test set according to the ratio of 8 : 2. The accuracy, sensitivity and specificity of the final classification model was 86.4%, 92.3% and 77.8%, respectively. At present, non-invasive screening method for vascular stiffness is very limited. The results of this study show that the characteristics of Korotkoff signal are affected by vascular compliance, and it is feasible to use the characteristics of Korotkoff signal to detect vascular stiffness. This study might be providing a new idea for non-invasive detection of vascular stiffness.

Purpose: The objective of this study is to develop a bleeding risk model for assessing device-induced bleeding risk in patients supported with blood contact medical devices (BCMDs)., Methods: The mathematical model for evaluating bleeding risk considers the effects of shear stress on von Willebrand factor (vWF) unfolding, high molecular weight multimers-vWF (HMWM-vWF) degradation, platelet activation and receptor shedding and platelet-vWF binding ability. Functions of the effect of shear stress on the above factors are fitted/employed and solved by the Eulerian transport equation. An axial flow-through Couette device and two clinical VADs which are HeartWare Ventricular Assist Device (HVAD) and HeartMate II (HM II) blood pump were employed to perform the simulation to evaluate platelet receptor shedding (GPIbα and GPIIb/IIIa), loss of HWMW-vWF, platelet-vWF binding ability and bleeding risk for validating the accuracy of our model., Results: The platelet-vWF binding ability after being subjected to high shear region in the axial flow-through Couette device predicted by our bleeding model was highly consistent with reported experimental data. As indicated by our CFD simulation results in the axial flow-through Couette device, it can find that an increase in shear stress led to a decrease in the adhesion ability of platelets on vWF, while the binding ability of vWF with platelets first increase and then decrease as shear stress elevates gradually beyond a threshold. The factor of exposure time can enhance the effect of shear stress. Additionally, the shear-induced bleeding risk predicted by our model increases with increasing shear stress and exposure time in an axial flow-through Couette device. As indicated by our numerical model, the bleeding risk in HVAD was higher than HMII, which is highly consistent with the meta-analysis based on clinical statistics. Our simulation investigations in these two clinical VADs also found that HVAD caused a higher rate of platelet receptor shedding and lower damage to HWMW-vWF than HeartMate II. The high shear stress generated in the narrow and turbulent regions of both VADs was the underlying cause of device-induced bleeding., Conclusion: In this study, the shear-induced bleeding risk predicted by our bleeding model in axial flow-through Couette device and two clinical VADs is consistent or highly correlated with experimental and clinical findings, which proves the accuracy of our bleeding model. Our bleeding model can be used to aid the development of new BCMDs with improved functional characteristics and biocompatibility, and help to reduce risk of device-induced adverse events in patients., Competing Interests: Declaration of Competing Interest There is no conflict of interest in this paper., (Copyright © 2023. Published by Elsevier B.V.)

To investigate the effect of rotor design configuration on hemodynamic features, hemocompatibility and dynamic balance of blood pumps. Computational fluid dynamics was employed to investigate the effects of rotor type (closed impeller, semi-open impeller), clearance height and back vanes on blood pump performance. In particular, the Eulerian hemolysis model based on a power-law function and the Lagrangian thrombus model with integrated stress accumulation and residence time were applied to evaluate the hemocompatibility of the blood pump. This study shows that compared to the closed impeller, the semi-open impeller can improve hemolysis at a slight sacrifice in head pressure, but increase the risk of thrombogenic potential and disrupt rotor dynamic balance. For the semi-open impeller, the pressure head, hemolysis, and axial thrust of the blood pump decrease with increasing front clearance, and the risk of thrombosis increases first and then decreases with increasing front clearance. Variations in back clearance have little effect on pressure head, but larger on back clearance, worsens hemolysis, thrombogenic potential and rotor dynamic balance. The employment of back vanes has little effect on the pressure head. All back vanes configurations have an increased risk of hemolysis in the blood pump but are beneficial for the improvement of the rotor dynamic balance of the blood pump. Reasonable back vanes configuration (higher height, wider width, longer length and more number) decreases the flow separation, increases the velocity of blood in the back clearance, and reduces the risk of blood pooling and thrombosis. It was also found that hemolysis index (HI) was highly negatively correlated with pressure difference between the top and back clearances (r = -.87), and thrombogenic potential was positively correlated with pressure difference between the top and back clearances (r = .71). This study found that rotor type, clearance height, and back vanes significantly affect the hydraulic performance, hemocompatibility and rotor dynamic balance of centrifugal blood pumps through secondary flow. These parameters should be carefully selected when designing and optimizing centrifugal blood pumps for improving the blood pump clinical outcomes., (© 2022 John Wiley & Sons Ltd.)

Introduction: The clavicular periosteum is a suitable material for trachea reconstruction. However, because the periosteum is softer and has different mechanical properties than tracheal cartilage, the mechanical loads under physiological conditions after trachea reconstruction may cause collapse or stenosis of the repaired trachea. Methods: In this study, the mechanical properties of the clavicular periosteum were tested, and the 3D trachea geometry was constructed based on CT-scanning images acquired before the surgery. Differing degrees of stenosis (0%, 33%, and 55%) for the repaired trachea sections were predetermined, presenting the different degrees of the tracheal cross-sectional area immediately after clavicular periosteum reconstruction. Then the biomechanical environments of the trachea and the airflow were simulated and analyzed. Results: In the fluid mechanics simulation, the air pressure on the patch area decreased with increasing degrees of stenosis, while the fluid velocity increased as stenosis increased. In solid mechanics simulations, patch area deformation increased as the cross-sectional area of the trachea decreased, and the stress in the patch increased as stenosis increased. Discussion: The solid stress changes may cause tissue remodeling, thickening, and scarring of the patch area. The fluid mechanical changes in the repaired trachea would further aggravate the stenosis. The numerical simulation study would provide references for biomechanical evaluation of trachea reconstruction surgery. The surgical indications may be expanded in the future based on the model prediction results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Sun, Xia, Chen, Sun and Chen.)

Background: The centrifugal blood pump volute has a significant impact on its hemodynamic performance hemocompatibility. Previous studies about the effect of volute design features on the performance of blood pumps are relatively few., Methods: In the present study, the computational fluid dynamics (CFD) method was utilized to evaluate the impact of volute design factors, including spiral start position, volute tongue radius, inlet height, size, shape and diffuser pipe angle on the hemolysis index and thrombogenic potential of the centrifugal blood pump., Results: Correlation analysis shows that flow losses affect the hemocompatibility of the blood pump by influencing shear stress and residence time. The closer the spiral start position of the volute, the better the hydraulic performance and hemocompatibility of the blood pump. Too large or too small volute inlet heights can worsen hydraulic performance and hemolysis, and higher volute inlet height can increase the thrombogenic potential. Small volute sizes exacerbate hemolysis and large volute sizes increase the thrombogenic risk, but volute size does not affect hydraulic performance. When the diffuser pipe is tangent to the base circle of the volute, the best hydraulic performance and hemolysis performance of the blood pump is achieved, but the thrombogenic potential is increased. The trapezoid volute has poor hydraulic performance and hemocompatibility. The round volute has the best hydraulic and hemolysis performance, but the thrombogenic potential is higher than that of the rectangle volute., Conclusion: This study found that the hemolysis index shows a significant correlation with spiral start position, volute size, and diffuser pipe angle. Thrombogenic potential exhibits a good correlation with all the studied volute design features. The flow losses affect the hemocompatibility of the blood pump by influencing shear stress and residence time. The finding of this study can be used to guide the optimization of blood pump for improving the hemodynamic performance and hemocompatibility., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Purpose: Device-induced blood damage contributes the hemolysis, thrombosis and bleeding complications in patients supported with ventricular assist device (VAD). This study aims to use a multi-indicator method to understand how devices causes blood damage and identify the "hot spots" of blood trauma within VADs., Methods: Computational fluid dynamics (CFD) methods were chosen to investigate the hemodynamic features of five clinical VADs (Impella 5.0, UltraMag, CHVAD, HVAD, and HeartMate II) under the same clinical support condition (flow rate of 4.5L/min, pressure head around 75 mmHg). A comprehensive multi-indicator evaluation method including hemodynamic parameters, hemolysis model, thrombotic potential model and bleeding probability model was used to analyze blood damage and assess the hemodynamic performance and hemocompatibility of these VADs., Results: Simulation results show that shear stress from 50 Pa to 100 Pa plays a major role in blood damage in Impella 5.0, UltraMag and CHVAD, while blood damage in HVAD and HeartMate II is mainly caused by shear stress greater than 100 Pa. Residence time was not the main factor for blood damage in Impella 5.0, and also makes a limited contribution to blood trauma in UltraMag and CHVAD, while it takes a critical role in elevating thrombotic potential in HVAD and HeartMate II. The distribution of regions of high hemolysis risk and high bleeding probability was similar for all these VADs and partially overlapped for high thrombotic potential regions. For Impella 5.0, regions with high hemolysis and bleeding risk were found mainly in the blade tip clearance and diffuser domains, high thrombotic potential regions were almost absent. For UltraMag, regions with high hemolysis, bleeding and thrombosis potential were found in two corners of the inlet pipe, the secondary flow passage, and the impeller eye. For CHVAD, the high-risk regions for hemolysis, bleeding and thrombosis are mainly in the inner side of the secondary flow passage and the middle region of the impeller passage. The narrow hydrodynamic clearance and impeller passage had a high risk of hemolysis and bleeding, and the clearance between the rotor and guide cone and the hydrodynamic clearance had high thrombotic potential. For HeartMate II, regions of high hemolysis risk and bleeding probability were found in the near-wall region of the straightener, the blade tip clearance and the diffuser domain. The corners of the inlet and outlet pipe and the straightener and diffuser regions had high thrombotic potential., Conclusion: The risk of hemolysis, bleeding and thrombosis for these five VADs, in increasing order, was Impella 5.0, UltraMag, CHVAD, HVAD, and HeartMate II. Flow losses caused by the rotor mechanical movement, chaotic flow and narrow clearances increase the blood damage for all these VADs. The multi-indicator analysis can comprehensively evaluate the VAD performance with improved assessment accuracy of CFD., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: A carotid web is a thin, shelf-like luminal protrusion in the internal carotid artery that might cause carotid stenosis and stroke by inducing disturbed flow patterns, thrombosis, and abnormal biomechanical stimulus to the endothelial cells. This study simulated and evaluated how the two main treatments (endarterectomy and stenting) influence hemodynamic environments in the carotid artery and distal carotid siphon arteries, aiming to provide more references for the selection of clinical treatment., Materials and Methods: The carotid web, endarterectomy, and stenting models were reconstructed based on CT images. The blood flow simulations were conducted, and critical parameters related to thrombosis formation and artery remodeling, including swirling strength, wall shear stress (WSS), vortex Q-criterion, and oscillating shear index (OSI), were analyzed., Results: In the model of the carotid web, obvious recirculation formed distal to the web, accompanied by lower velocity, lower WSS, higher relative resident time (RRT), and higher Q value. While in both two treatment models, the velocity increased and the Q value and RRT decreased at the carotid bifurcation. In addition, both treatments provide more kinetic energy to the distal carotid siphon artery, especially the stenting model., Conclusion: The carotid web can significantly influence the flow environments in the carotid artery. Both endarterectomy and stenting treatments could significantly diminish the side effects of the web and are feasible choices for web patients in terms of hemodynamics. Besides, the treatments for the carotid web would also influence the flow patterns at the distal carotid siphon, especially for the stenting treatment. But more innovational designs are needed to make the minimally invasive stenting treatment more beneficial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ren, Liu, Chen, Deng, Sun and Luan.)

Purpose: The purpose of this study was to investigate the impact of a new arterial intravascular pump on the hemodynamic surroundings within the aorta. Methods: A new arterial intravascular pump was placed in the descending aorta, and the effects of three positions within the aorta, as well as the number (n = 1 to 3) of pumps, on arterial flow features, organ perfusion, and blood trauma were investigated using a computational fluid dynamics (CFD) method. Results: It was found that as the pump position was moved backward, the perfusion in the three bifurcated vessels of the aorta arch increased and the pump suction flow decreased, resulting in a reduced high shear stress and decreased residence time in the three branches of the aortic arch. The further posterior the location of the pump, the better the blood flow perfusion to the kidneys, while the perfusion at the bifurcation of the abdominal aorta was reduced, due to the pump suction effect. Compared to the condition with single pump support, the multi-pump assist model can significantly reduce the pump rotating speed, while keeping the same flow patterns, leading to a decreased volume of high shear stress and flow loss. When increasing the number of pumps, the perfusion to the three branches of the aortic arch increased, accompanied by a diminished residence time, and the perfusion to the other aortic branches was decreased. However, the perfusion to the other aortic branches, especially for the renal arteries and even under a three-pump condition, was close to that without pump assistance. Conclusion: The placement of an intravascular pump near the beginning of the suprarenal abdominal aorta was considered the optimal location, in order to improve the hemodynamic surroundings. Increasing the number of pumps can significantly reduce the rotational speed, while maintaining the same flowrate, with a decreased fluid energy loss and a reduced high shear stress. This arterial intravascular pump can effectively improve renal blood flow.

Most small diameter vascular grafts (inner diameter<6 mm) evaluation studies are performed in healthy animals that cannot represent the clinical situation. Herein, an hypercholesterolemia (HC) rat model with thickened intima and elevated expression of pro-inflammatory intercellular adhesion molecular-1 (ICAM-1) in the carotid branch is established. Electrospun polycaprolactone (PCL) vascular grafts (length: 1 cm; inner diameter: 2 mm) are implanted into the HC rat abdominal aortas in an end to end fashion and followed up to 43 days, showing a relative lower patency accompanied by significant neointima hyperplasia, abundant collagen deposition, and slower endothelialization than those implanted into healthy ones. Moreover, the proliferation, migration, and adhesion behavior of endothelial cells (ECs) isolated from the HC aortas are impaired as evaluated under both static and pulsatile flow conditions. DNA microarray studies of the HC aortic endothelium suggest genes involved in EC proliferation (Egr2), apoptosis (Zbtb16 and Mt1), and metabolism (Slc7a11 and Hamp) are down regulated. These results suggest the impaired proliferative, migratory, and adhesive abilities of ECs are associated with the bad performances of grafts in HC rat. Future pre-clinical evaluation of small diameter vascular grafts may concern more disease animal models with clinical complications. STATEMENT OF SIGNIFICANCE: During the development of small diameter vascular grafts (D<6 mm), young and healthy animal models from pigs, sheep, dogs, to rabbits and rats are preferred. However, it cannot represent the clinic situation, where most cardiovascular grafting procedures are performed in the elderly and age is the primary risk factor for disease development or death. Herein, the performance of electrospun polycaprolactone (PCL) vascular grafts implanted into hypercholesterolemia (HC) or healthy rats were evaluated. Results suggest the proliferative, migratory, and adhesive abilities of endothelial cells (ECs) are already impaired in HC rats, which contributes to the observed slower endothelialization of implanted PCL grafts. Future pre-clinical evaluation of small diameter vascular grafts may concern more disease animal models with clinical complications., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

(1) Background: Thrombosis is the main complication in patients supported with ventricular assist devices (VAD). Models that accurately predict the risk of thrombus formation in VADs are still lacking. When VADs are clinically assisted, their complex geometric configuration and high rotating speed inevitably generate complex flow fields and high shear stress. These non-physiological factors can damage blood cells and proteins, release coagulant factors and trigger thrombosis. In this study, a more accurate model for thrombus assessment was constructed by integrating parameters such as shear stress, residence time and coagulant factors, so as to accurately assess the probability of thrombosis in three clinical VADs. (2) Methods: A mathematical model was constructed to assess platelet activation and thrombosis within VADs. By solving the transport equation, the influence of various factors such as shear stress, residence time and coagulation factors on platelet activation was considered. The diffusion equation was applied to determine the role of activated platelets and substance deposition on thrombus formation. The momentum equation was introduced to describe the obstruction to blood flow when thrombus is formed, and finally a more comprehensive and accurate model for thrombus assessment in patients with VAD was obtained. Numerical simulations of three clinically VADs (CH-VAD, HVAD and HMII) were performed using this model. The simulation results were compared with experimental data on platelet activation caused by the three VADs. The simulated thrombogenic potential in different regions of MHII was compared with the frequency of thrombosis occurring in the regions in clinic. The regions of high thrombotic risk for HVAD and HMII observed in experiments were compared with the regions predicted by simulation. (3) Results: It was found that the percentage of activated platelets within the VAD obtained by solving the thrombosis model developed in this study was in high agreement with the experimental data (r² = 0.984), the likelihood of thrombosis in the regions of the simulation showed excellent correlation with the clinical statistics (r² = 0.994), and the regions of high thrombotic risk predicted by the simulation were consistent with the experimental results. Further study revealed that the three clinical VADs (CH-VAD, HVAD and HMII) were prone to thrombus formation in the inner side of the secondary flow passage, the clearance between cone and impeller, and the corner region of the inlet pipe, respectively. The risk of platelet activation and thrombus formation for the three VADs was low to high for CH-VAD, HVAD, and HM II, respectively. (4) Conclusions: In this study, a more comprehensive and accurate thrombosis model was constructed by combining parameters such as shear stress, residence time, and coagulation factors. Simulation results of thrombotic risk received with this model showed excellent correlation with experimental and clinical data. It is important for determining the degree of platelet activation in VAD and identifying regions prone to thrombus formation, as well as guiding the optimal design of VAD and clinical treatment.

The degradation time is a crucial factor in evaluating the performance of poly (lactic-co-glycolic acid) (PLGA) stents. Bulk degradation mode was commonly used to analyze the stent degradation behavior by finite element approach. However, the PLGA stents may present surface degradation more than bulk degradation under certain conditions, which will greatly affect the degradation time after implantation. In this study, the degradation processes of the poly (lactic-co-glycolic acid) stent were reproduced utilizing finite element analysis. Both bulk degradation and surface degradation modes were considered. The correlation between tensile stress and degradation rate was investigated. The degradation time was analyzed selectively. The stress distribution, fracture, and mass loss were also compared between bulk degradation mode and surface degradation mode. The simulation results showed that, in both evolution modes, the degradation began at the 'peak-valley' region and fracture occurred at the cross of links and rings. Additionally, high levels of Von-Mises stress were observed in these two regions. Compared with bulk degradation, the fracture time of the stent was delayed by 63% in the surface degradation mode. In conclusion, the mass loss rate and scaffolding period showed great differences between surface degradation and bulk degradation. Based on this study, it is suggested that bulk degradation mode is not applicable to the case of inadequate water uptake mode, such as the tracheal stent degradation process. More experimental research should be carried out to accurately predict the scaffolding period after implantation. The mechanical properties of the fracture zone should be strengthened.

In accordance with "the response to injury" theory, the entry of monocytes into the intima guided by inflammation signals, taking up cholesterol and transforming into foam cells, and egress from plaques determines the progression of atherosclerosis. Multiple cytokines and receptors have been reported to be involved in monocyte recruitment such as CCL2/CCR2, CCL5/CCR5, and CX3CL1/CX3CR1, and the egress of macrophages from the plaque like CCR7/CCL19/CCL21. Interestingly, some neural guidance molecules such as Netrin-1 and Semaphorin 3E have been demonstrated to show an inhibitory effect on monocyte migration. During the processes of monocytes recruitment and migration, factors affecting the biomechanical properties (e.g., the membrane fluidity, the deformability, and stiffness) of the monocytes, like cholesterol, amyloid- β peptide (A β ), and lipopolysaccharides (LPS), as well as the biomechanical environment that the monocytes are exposed, like the extracellular matrix stiffness, mechanical stretch, blood flow, and hypertension, were discussed in the latter section. Till now, several small interfering RNAs (siRNAs), monoclonal antibodies, and antagonists for CCR2 have been designed and shown promising efficiency on atherosclerosis therapy. Seeking more possible biochemical factors that are chemotactic or can affect the biomechanical properties of monocytes, and uncovering the underlying mechanism, will be helpful in future studies., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Hongyan Kang et al.)

The surface of vascular endothelial cells (ECs) is covered by a protective negatively charged layer known as the endothelial glycocalyx. Herein, we hypothesized its transport barrier and mechanosensory role in transmural water flux and low-density lipoprotein (LDL) transport in an isolated rat abdominal aorta perfused under 85 mmHg and 20 dyn/cm 2 ex vivo. The endothelial glycocalyx was digested by hyaluronidase (HAase) from bovine tests. Water infiltration velocity ( V w ) was measured by a graduated pipette. LDL coverage and mean maximum infiltration distance (MMID) in the vessel wall were quantified by confocal laser scanning microscopy. EC apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) technique, and leaky junction rates were evaluated by electron microscopy. The results showed that a 42% degradation of the endothelial glycocalyx by HAase treatment increased V w , LDL coverage, and MMID. Shear stress increased V w , which cannot be inhibited by HAase treatment. Four hour-shear application increased about fourfolds of LDL coverage, whereas exerted no significant effects on its MMID, EC apoptosis, and the leaky junctions. On the contrary, 24-h shear exposure has no significant effects on LDL coverage, whereas increased 2.74-folds of MMID and about 53% of EC apoptotic rates that could be inhibited by HAase treatment. These results suggest endothelial glycocalyx acts as a transport barrier by decreasing water and LDL transport, as well as a mechanosensor of shear to regulate EC apoptosis, thus affecting leaky junctions and regulating LDL transport into the vessel wall. NEW & NOTEWORTHY A 42% degradation of the endothelial glycocalyx by hyaluronidase of the isolated rat abdominal aorta facilitated water and LDL transport across the vessel wall, suggesting endothelial glycocalyx as a transport barrier. A 24-h shear exposure increased LDL mean maximum infiltration distance, and enhanced EC apoptosis, which could be both inhibited by hyaluronidase treatment, suggesting endothelial glycocalyx may also act as a mechanosensor of shear to regulate EC apoptosis, thus affecting leaky junctions and regulating LDL transport.

Endothelial cells (ECs) in vivo are subjected to three forms of shear stress induced by luminal blood flow, transendothelial flow and interstitial flow simultaneously. It is controversial that shear stress, especially the component induced by luminal flow, was thought to inhibit the initialization of angiogenesis and trigger arteriogenesis. Here, we combined microfabrication techniques and delicate numerical simulations to reconstruct the initial physiological microenvironment of neovascularization in vitro, where ECs experience high luminal shear stress, physiological transendothelial flow and various vascular endothelial growth factor (VEGF) distributions simultaneously. With the biomimetic microfluidic model, cell alignment and endothelial sprouting assays were carried out. We found that luminal shear stress inhibits endothelial sprouting and tubule formation in a dose-dependent manner. Although a high concentration of VEGF increases EC sprouting, neither a positive nor a negative VEGF gradient additionally affects the degree of sprouting, and luminal shear stress significantly attenuates neovascularization even in the presence of VEGF. Heparinase was used to selectively degrade the heparan sulfate proteoglycan (HSPG) coating on ECs and messenger RNA profiles in ECs were analyzed. It turned out that HSPGs could act as a mechanosensor to sense the change of fluid shear stress, modulate multiple EC gene expressions, and hence affect neovascularization. In summary, distraction from the stabilized state, such as decreased luminal shear stress, increased VEGF and the destructed mechanotransduction of HSPGs would induce the initiation of neovascularization. Our study highlights the key role of the magnitude and forms of shear stress in neovascularization.

Biodegradable stents (BDSs) are the milestone in percutaneous coronary intervention(PCI). Biodegradable polymeric stents have received widespread attention due to their good biocompatibility, moderate degradation rate and degradation products without toxicity or side effects. However, due to the defects in mechanical properties of polymer materials, the clinical application of polymeric BDS has been affected. In this paper, the BDS geometric configuration design was analyzed to improve the radial strength, flexibility and reduce the shrinkage rate of biodegradable polymeric stents. And from the aspects of numerical simulation, in vitro experiment and animal experiment, the configuration design and mechanical properties of biodegradable polymeric stents were introduced in detail in order to provide further references for the development of biodegradable polymeric stents.

Hypercholesterolemia- and atherosclerosis-caused vasomotor property dysfunction may be involved in many clinic manifestations of atherosclerosis, including angina, acute myocardial infarction, and sudden cardiac death. However, its underlying mechanism is not clear. The endothelial glycocalyx is a protective surface layer on the endothelial cells, serving as a molecular sieve, cell adhesion modulator, and mechanosensor for blood flow. In the present study, we demonstrated by confocal microscopy in Sprague-Dawley (SD) male rats fed a 12-wk high-cholesterol diet (HC) compared with the normal diet (NC) that the dimension of the endothelial glycocalyx reduced significantly in both the common carotid artery (2.89 ± 0.41 µm and 3.25 ± 0.44 μm, respectively) and the internal sinus region (2.35 ± 0.07 µm and 3.46 ± 0.86 μm, respectively). Furthermore, we showed by real-time PCR that this dimension modification of endothelial glycocalyx may be attributed to a significant downregulation of heparan sulfate proteoglycan (HSPG)-related genes, including syndecan-3, glypican-1, and EXT1, not resulting from an enhanced shedding of sulfated glycosaminoglycans (sGAGs) from the vessel wall to the plasma. Meanwhile, the mean contraction and relaxation forces of the common carotid artery with responses to norepinephrine (NE) and acetylcholine (ACh) decreased ~0.34- and 0.13-fold, respectively, accompanied by a lower level of nitric oxide (NO) release. These findings suggest that the atherogenic high cholesterol diet diminished endothelial glycocalyx and disturbed the local NO release, thus contributing to the impaired vasomotor properties of the vessel. NEW & NOTEWORTHY Twelve-week high-cholesterol (HC) diet reduces the thickness of the endothelial glycocalyx in Sprague-Dawley (SD) male rats, which is mainly attributed to a downregulation of heparan sulfate proteoglycan-related genes (syndecan-3, glypican-1, EXT1), not resulting from an enhanced shedding of sulfated glycosaminoglycans (sGAGs) into the plasma. HC-diminished glycocalyx may disturb its mechanotransduction of local shear stress, lower nitric oxide (NO) release, and impair vasomotor responses to norepinephrine (NE) and acetylcholine (ACh).

Background: Gender difference in cardiovascular diseases (CVDs) is an important topic in the field of cardiovascular medicine. In this study, we focused on the mortality difference of abdominal aortic aneurysms (AAA), which is higher for female than that of male. The aim of this study was to verify whether morphological and hemodynamic factors play their roles in this phenomenon., Methods: Patient-specific AAA models of 11 females and 23 males with similar age and body mass index (BMI) have been reconstructed based on clinical computed tomography (CT) data. Firstly, the morphological parameters (diameters, curvature, intraluminal thrombus volume, etc.) of AAA models and lumbar vertebrae models were collected and analyzed. Then, based on statistical results of morphological parameters, uniformed male and female AAA models were reconstructed, and hemodynamic simulations were conducted respectively. In post-processing, the hemodynamic performances induced by gender-different morphological geometries were analyzed and compared., Results: The comparison of morphological parameters revealed that the average curvature of lumbar vertebrae and AAA centerline of female AAA models were obviously higher than that of the male. The amount of intraluminal thrombus in female AAA models was relatively lower than that of the male. According to the hemodynamic simulation, the uniform female AAA model has higher peak pressure, lower oscillatory shear stress index (OSI), and lower relative residence time (RRT) than that of the male model, all of which put female AAA to a relatively higher risk hemodynamic situation., Conclusions: The morphological and hemodynamic features of AAA have very obvious gender differences that would induce higher risk of rupture for female AAA biomechanically. These findings would help to explore the mechanism of gender differences in AAA and draw attention to gender-specific consideration for AAA treatment. More morphological and hemodynamic indictors are suggested to be involved in the future guidelines.

Objectives: The study investigates local hemodynamic environment changes caused by straightening phenomenon and the relationship between straightening phenomenon and in-stent restenosis., Background: Intravascular intervention is an effective treatment in restoring the normal flow conditions and vascular lumen. Unfortunately, in-stent restenosis often occurs in a subset of patients after stent implantation and limits the success of stent implantation outcomes. The implanted stent usually causes artery straightening locally, rather than coinciding and adjusting to the physiological curve exactly. Artery straightening would apparently modify the artery geometry and therefore alter the local hemodynamic environment, which may result in intimal hyperplasia and restenosis after stenting implantation., Methods: In the current investigation, we verify the hypothesis that the artery straightening influences the local hemodynamic state using the different 3D CT models. Flow analysis for blood in the left anterior descending coronary artery and the straightening model is simulated numerically., Result: The current results reveal that the straightening phenomenon alters the distribution of wall shear stress and flow patterns, decreases the wall shear stress (WSS), and increases the oscillatory shear index (OSI) and the relative residence time (RRT), especially at the proximal and distal areas of stenting., Conclusions: The local straightened geometry established after stent implantation was likely to generate portions of the stenting area to a high risk of neointimal hyperplasia and subsequent restenosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Pengfei Liu et al.)

Among the interventional stenting methods for treating coronary bifurcation lesions, the conventional treatments still have disadvantages, which include increased intervention difficulties or inadequate supply of blood flow to side branches and may alter the physiological function of downstream organs. Thus, the optimized design of stent geometry needs to be improved based on the specific shape of branches to minimize the complications of inadequate blood flow to the downstream organs and tissues. Our research used 3D modeling and fluid dynamics simulation to design and evaluate a new stent with locally enlarged segment by altering the proportion and length of enlarged surface area based on Bernoulli's equation. The aim is to increase the pressure and blood flow supply at side branches. According to series of blood flow simulations, the stent with 10% enlargement of surface area and length of 3 folders of stent diameter was assigned as the optimized design. The results revealed that by using this design, according to the simulation results, the average pressure on side branches increased at the rate of 43.6%, which would contribute to the adequate blood supply to the downstream organs. Besides, the average wall shear stress (WSS) at sidewalls increased at 9.2% while the average WSS on the host artery wall decreased at 14.1%. There is in the absent of noticeable rise in the total area of low WSS that blows the threshold of 0.5 Pa. Therefore, the present study provides a new method to optimize the hemodynamics features of stent for bifurcation arteries., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Yudi Niu et al.)

The importance of vascular cell glycocalyx in mechanotransduction has been demonstrated by many studies. The simulated microgravity induced a region-dependent adaptation of arterial glycocalyx including its thickness, coverage, and gene expression in conduit arteries of tail-suspended rats has been reported in our previous studies. Herein, we extended this line of research by quantifying the mRNA levels of three nitric oxide synthase (NOSI, NOSII, and NOSIII) and evaluating the apoptotic rates of endothelial cells (ECs) and smooth muscle cells (SMCs) in the common carotid artery, abdominal aorta, and femoral artery of 3 week tail-suspended rats. Results indicated that the tail suspension of rats induced about 0.36, 0.22, and 0.33 fold down-regulation of NOSI, NOSII, and NOSIII in the abdominal aorta, while 3.21, and 3.48 fold up-regulation of NOSII and NOSIII in the carotid artery and no significant effects on three NOS isoforms in the femoral artery. Moreover, the apoptosis of ECs and SMCs were significantly inhibited in both carotid artery and abdominal aorta, while enhanced in the femoral artery of the tail-suspended rats. A linear positive correlation exists between the normalized coverage of the glycocalyx and the normalized NOSI and NOSIII mRNA levels. These results indicated that the redistribution of haemodynamics in the conduit arteries of 3 week tail-suspended rats regulated the glycocalyx, NOS expression, and vascular cell apoptosis in a region-dependent manner, contributing to the final vascular remodelling under simulated microgravity condition., (© 2019 John Wiley & Sons Australia, Ltd.)

Objectives: Postoperative pancreatic fistula (POPF) is a major concern after pancreatoduodenectomy (PD). We recently designed a new anastomotic method to reduce the rate of pancreatic fistula: polytetrafluoroethylene suture buttress-reinforced pancreaticojejunostomy (PBRP)., Methods: An animal model and a computer simulation were used to measure the maximum stress and tensile strength of the pancreas with and without the suture buttresses. Then, a randomized controlled trial (RCT) was performed to compare the outcome of PD between patients who underwent PBRP vs traditional pancreaticojejunostomy (TP)., Results: The maximum load in the animal model was significantly higher with the suture buttresses than without (5.47 ± 1.67 N vs 3.72 ± 1.36 N, p < 0.01), and in the computer simulation, the peak stress was lower with the suture buttresses than without (54.86 vs 486.8 MPa). There were no significant differences between the two groups in the overall frequency of POPF, but the rate of clinically relevant POPF was significantly lower in the PBRP group (2.8 vs 22.8%, p = 0.028). The pancreaticojejunostomy time was significantly longer in the PBRP group (19.57 ± 3.31 vs 17.17 ± 4.83 min, p = 0.018), and the PBRP group showed a shorter drainage tube retention duration (10 vs 12 days, p = 0.006) and postoperative hospital stay (13 d vs 15 d, p = 0.031)., Conclusions: PBRP is a feasible and reliable procedure for preventing clinically relevant POPF. Additional multi-institution randomized trials should be conducted to confirm these results.

Thoracic aortic aneurysm (TAA) is fatal diseases, which leads to aortic rupture and sudden death. Blood pressure-lowering drugs are ineffective for most of the patients. Our previous study demonstrated the inhibition of endothelial secreted miR-126-3p by rapamycin ameliorate the aneurysmal phenotype of smooth muscle cells (SMCs) in vitro. Hence, this study aimed to evaluate the modulation and mechanism of miR-126-3p in a murine model of TAA (Fbn1 C1039G/+ ). Our results showed that noticeable disturbed flow (DF) was observed in the aorta of Fbn1 C1039G/+ mice, and the expression of miR-126-3p was significantly increased under the DF in the cell chamber. This finding was also confirmed by tests in the corresponding DF area of the human aortic aneurysm tissue. Constant rapamycin administration significantly ameliorates the incidence and severity of Fbn1 C1039G/+ mice characterized by decreased aortic media degradation, macrophage infiltration and MMP2/9 expression in the aortic wall. Mechanistic studies showed that rapamycin attenuates TAA progression by inhibiting miR-126-3p through ERK1/2 inactivation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Blood flow condition may have influence upon the hydraulic conductivity of venous graft (L p,vein ) in an arterial bypass, then affecting the accumulation of low-density lipoproteins (LDLs) within the graft wall. To probe this possibility, we first measured in vitro the filtration rates of swine lateral saphenous vein segments under different flow rates, and the correlation of L p,vein with wall shear stress (WSS) was then obtained., Results: The experimental results showed that when WSS was very low, L p,vein would increase drastically with WSS from 1.16 ± 0.15 × 10 -11 m/s Pa at 0 dyn/cm 2 to 2.17 ± 0.20 × 10 -11 m/s Pa at 0.7 dyn/cm 2 , then became constant of approximately 2.33 × 10 -11 m/s Pa as the WSS increased further. Based on the experimental results, we assumed three different cases of L p,vein and numerically simulated the LDLs transport in an arterial bypass model with venous graft. Case A: L p,vein  = 2.33 × 10 -11 m/s Pa; Case B: L p,vein  = 1.16 × 10 -11 m/s Pa (static condition with WSS of 0); Case C: L p,vein was shear dependent. The simulation showed that the deposition/accumulation of LDLs within the venous graft wall in Case A was greatly enhanced when compared with that in Case B. However, the LDL accumulation in the graft wall was similar for Case A and Case C., Conclusions: Our study, therefore, indicates that when the venous graft was implanted as a bypass graft, the L p,vein might remain nearly constant along its whole length except for very few areas where the value of WSS was extremely low (less than 0.7 dyn/cm 2 ) and the effects of L p,vein modulated by blood flow on LDL transport may be neglected.

The phenomenon of sex differences exists in patients who have abdominal aortic aneurysms (AAA). The occurrence rate of AAA is higher in male, while the rates of rupture and postoperative mortality are higher for female. This phenomenon of sex differences would affect the diagnosis, treatment and postoperative rehabilitation for AAA patients. This article reviewed the recent research status of sex differences on AAA, and explored the phenomenon of sex differences from the aspects of threshold determination, biomechanics and mechanobiology. This review points out that the sex differences on AAA could ascribe to the differences of biomechanical environment and biological properties induced by the vascular size, anatomy structure and structure components of abdominal aortic artery. The comprehensive investigations of the sex differences on AAA could help to optimize the diagnosis, treatment and device design, patient care and rehabilitation strategy of AAA based on sex differences phenomenon.

The typical helical flow within the human arterial system is widely used when designing cardiovascular devices, as this helical flow can be generated using the "crossed limbs" strategy of the bifurcated stent graft (BSG) and enhanced by the tapered structure of arteries. Here, we propose the use of a deflected blended bifurcated stent graft (BBSG) with various tapers, using conventional blended BSGs with the same degree of taper as a comparison. Hemodynamic performances, including helical strength and wall shear stress- (WSS-) based indicators, were assessed. Displacement forces that may induce stent-graft migration were assessed using numerical simulations and in vitro experiments. The results showed that as the taper increased, the displacement force, helicity strength, and time-averaged wall shear stress (TAWSS) within the iliac grafts increased, whereas the oscillating shear index (OSI) and relative residence time (RRT) gradually decreased for both types of BBSGs. With identical tapers, deflected BBSGs, compared to conventional BBSGs, exhibited a wider helical structure and lower RRT on the iliac graft and lower displacement force; however, there were no differences in hemodynamic indicators. In summary, the presence of tapering facilitated helical flow and produced better hemodynamic performance but posed a higher risk of graft migration. Conventional and deflected BBSGs with taper might be the two optimal configurations for endovascular aneurysm repair, given the helical flow. The deflected BBSG provides a better configuration, compared to the conventional BBSG, when considering the reduction of migration risk.

The "crossed limbs" strategy for bifurcated stent grafts (BSGs) is widely employed when abdominal aortic aneurysm (AAA) patients have unfavorable neck or highly splayed iliac arteries. Helical flow is regarded as a typical flow pattern within the human arterial system and is believed to have the positive physiological effects of inhibiting thrombosis formation and atherosclerosis. The "crossed limbs" strategy may induce helical flow and improve the stent graft outcome. To verify the performance of this strategy by considering hemodynamics, we constructed a series of idealized BSGs with various torsion angles and evaluated the hemodynamic performance, including the helical strength, time-averaged wall shear stress (TAWSS), oscillatory shear index, relative resident time (RRT), and displacement force. Our numerical results indicate that an increased torsion angle enhances the helicity strength at the iliac outlets. However, with increasing torsion angle, the TAWSS in the iliac graft decreases and the RRT increases. In addition, our numerical simulations and in vitro experiments reveal that the displacement force increases gradually with increasing torsion angle. In summary, the "crossed limbs" strategy may have benefits for AAA treatment in terms of helical flow, but because of the unfavorable hemodynamic performance verified by analyzing the hemodynamic indicators, the risk of stent graft migration increases with increasing torsion angle. Therefore, the "crossed limbs" strategy should be carefully employed in surgical AAA treatment.

Cancer is a malignant tumor that threatens the health of human beings, and has become the leading cause of death in urban and rural residents in China. The glycocalyx is a layer of multifunctional glycans that covers the surfaces of a variety of cells, including vascular endothelial cells, smooth muscle cells, stem cells, epithelial, osteocytes, as well as cancer cells. The glycosylation and syndecan of cancer cell glycocalyx are unique. However, heparan sulfate (HS), hyaluronic acid (HA), and syndecan are all closely associated with the processes of cancer progression, including cell migration and metastasis, tumor cell adhesion, tumorigenesis, and tumor growth. The possible underlying mechanisms may be the interruption of its barrier function, its radical role in growth factor storage, signaling, and mechanotransduction. In the later sections, we discuss glycocalyx targeting therapeutic approaches reported in animal and clinical experiments. The study concludes that cancer cells' glycocalyx and its role in cancer progression are beginning to be known by more groups, and future studies should pay more attention to its mechanotransduction of interstitial flow-induced shear stress, seeking promising therapeutic targets with less toxicity but more specificity.

Background and Aims: The crossed limbs stent graft technique is regularly employed to treat abdominal aortic aneurysm patients with unfavorable aneurysm necks or widely splayed common iliac arteries. This article numerically evaluates the hemodynamic performance of the crossed limbs strategy by analyzing numerical simulations and conducting experiments using two series of idealized bifurcated stent grafts with different cross angles and cross positions., Results: Results demonstrated that the absolute helicity at outlets decreased with increased cross angles and increased with decreased cross positions. The time-averaged wall shear stress remained approximately unchanged, whereas the oscillating shear index and relative resident time decreased slightly when the cross angle increased and cross position decreased in iliac grafts. Additionally, both numerical and in vitro experimental results indicate the displacement force acting on the stent graft gradually increased as cross angles increased and cross positions decreased. Results further indicated that strip areas with a high oscillating shear index and high relative resident time, which may be vulnerable to thrombosis formation, exist along the outer surface of the iliac artery grafts., Conclusion: Given this information, the optimal crossed limbs configuration may contain a small cross angle and low cross position; however, low cross positions may increase the risk of migration.

Vascular remodeling induced by hemodynamic stimuli contributes to the pathophysiology of cardiovascular diseases. The importance of vascular cells (endothelial cells and smooth muscle cells) glycocalyx in the mechanotransduction of flow-induced shear stress at the cellular and molecular levels has been demonstrated over the past decade. However, its potential mechanotransduction role in vascular remodeling has triggered little attention. In the present study, a home-made apparatus was used to expose the rat abdominal aorta to sterile, flow or no flow, normal-pressure or high-pressure conditions for 4 days. The histomophometric, cellular, and molecular analysis of vessels were performed. The results showed that after exposing the vessels in the flow and high-pressure condition, the apoptotic rate, the cell number, and the RNA level of contractile marker gene smooth muscle 22 of smooth muscle cells were significantly increased, whereas the expression of nitric oxide synthase, α-smooth muscle actin, smoothelin, and calponion showed no significant differences compared with the flow and normal-pressure groups. Moreover, the histomophometric analysis of vascular walls suggested a remodeling induced by flow and high-pressure loading consistent with the classic hypertensive aortic phenotype, which is characterized by a thicker and more rigid vascular wall as well as increased aortic diameter. However, those phenomena were totally abolished after compromising the integrity of glycocalyx by the treatment of vessels with hyaluronidase, which provided evidence of the important mechanotransduction role of the vascular cells glycocalyx in vascular remodeling induced by hemodynamic stimuli., (© 2018 American Heart Association, Inc.)

Longitudinal anatomic mismatch (LAM) of stenting (i.e., a stenotic artery segment is not fully covered by a deployed stent) worsens the mechanical environment in the treated artery, which most likely is the cause for the associated high risks of restenosis, myocardial infarction and stent thrombosis. To probe the possibility, we constructed a patient-specific carotid model with two components of plaques (lipid and calcified plaque) based on MRI images; we numerically compared three different stenting scenarios in terms of von Mises stress (VMS) distribution in the treated arteries, namely, the short stenting (LAM), the medium stenting and the long stenting. The results showed that the short stenting led to more areas with abnormally high VMS along the inner surface of the treated artery with a much higher surface-averaged VMS at the distal end of the stent than both the medium and long stenting. While the VMS distribution in the calcified plaques was similar for the three stenting models, it was quite different in the lipid plaques among the three stenting models. The lipid plaque of the short-stent model showed more volume of the lipid plaque subjected to high VMS than those of the other two models. Based on the obtained results, we may infer that the short stenting (i.e., LAM) may aggravate vascular injury due to high VMS on the artery-stent interaction surface and within the lipid plaque. Therefore, to obtain a better outcome, a longer stent, rather than a short one, might be needed for arterial stenting., (Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.)

Two mechanisms of shear stress and mass transport have been recognized to play an important role in the development of localized atherosclerosis. However, their relationship and roles in atherogenesis are still obscure. It is necessary to investigate quantitatively the correlation among low-density lipoproteins (LDL) transport, haemodynamic parameters and plaque thickness. We simulated blood flow and LDL transport in rabbit aorta using computational fluid dynamics and evaluated plaque thickness in the aorta of a high-fat-diet rabbit. The numerical results show that regions with high luminal LDL concentration tend to have severely negative haemodynamic environments (HEs). However, for regions with moderately and slightly high luminal LDL concentration, the relationship between LDL concentration and the above haemodynamic indicators is not clear cut. Point-by-point correlation with experimental results indicates that severe atherosclerotic plaque corresponds to high LDL concentration and seriously negative HEs, less severe atherosclerotic plaque is related to either moderately high LDL concentration or moderately negative HEs, and there is almost no atherosclerotic plaque in regions with both low LDL concentration and positive HEs. In conclusion, LDL distribution is closely linked to blood flow transport, and the synergetic effects of luminal surface LDL concentration and wall shear stress-based haemodynamic indicators may determine plaque thickness., (© 2017 The Author(s).)

The vascular smooth muscle cells (VSMCs) are exposed to interstitial flow induced shear stress that may be sensed by the surface glycocalyx, a surface layer composed primarily of proteoglycans and glycoproteins, to mediate cell contraction during the myogenic response. We, therefore, attempted to elucidate the signal pathway of the glycocalyx mechanotransduction in shear stress regulated SMC contraction. Human umbilical vein SMCs (HUVSMCs) deprived of serum for 3-4 days were exposed to a step increase (0 to 20 dyn/cm 2 ) in shear stress in a parallel plate flow chamber, and reduction in the cell area was quantified as contraction. The expressions of Rho kinase (ROCK) and its downstream signal molecules, the myosin-binding subunit of myosin phosphatase (MYPT) and the myosin light chain 2 (MLC2), were evaluated. Results showed that the exposure of HUVSMCs to shear stress for 30 min induced cell contraction significantly, which was accompanied by ROCK1 up-regulation, re-distribution, as well as MYPT1 and MLC activation. However, these shear induced phenomenon could be completely abolished by heparinase III or Y-27632 pre-treatment. These results indicate shear stress induced VSMC contraction was mediated by cell surface glycocalyx via a ROCK-MLC phosphatase (MLCP) pathway, providing evidence of the glycocalyx mechanotransduction in myogenic response., Competing Interests: The authors declare no competing financial interests.

Background: Abdominal aortic aneurysm (AAA) is a kind of dangerous aortic vascular disease, which is characterized by abdominal aorta partial enlargement. At present, endovascular aneurysm repair (EVAR) is one of the main treatments of abdominal aortic aneurysm. However for some patients after EVAR the aneurysm re-expanded and even ruptured, leading to poor postoperative effect. The stent-graft endoleak after EVAR was realized to influence the AAA in-sac pressure and contribute to the aneurysm re-enlargement., Methods: In order to analyze the influence of endoleaks positions on the pressure shielding ability of stent-graft after EVAR, type I and type III endoleak models were reconstructed based on computed tomography (CT) scan images, and the hemodynamic environment in AAA was numerically simulated., Results: When the endoleak was at the proximal position the pressure shielding ability will be obviously weakened. While, the pressure shielding ability was higher in the systole phase than that in diastole phase when the endoleak located at the middle or distal positions. Unfortunately, when the endoleak located at the proximal position, the pressure shielding ability would be relatively weak in the whole cardiac cycle., Conclusions: The results revealed that the influence of endoleaks on pressure shielding ability of stent-graft was both location and time specific.

Helical flow has been introduced to improve the hemodynamic performance of vascular devices such as arterial grafts, stents and arteriovenous shunts to overcome the flow induced thrombus formation and intimal hyperplasia. However, the quite low intensity of helical flow in the existing devices may limit their function. To obtain desirably high intensity, inspired by the helical flow and tapered configuration of the arterial system, we proposed a new conceptual design of the medical devices, which take the form of a tapered helical shape. We demonstrated its effectiveness in arterial grafts by numerically comparing the hemodynamic performance of helical grafts with different smooth tapers. The results show that the helicity density quantifying the helical flow enlarges sharply with the increase of the taper under both steady and pulsatile flow conditions. Moreover, the amplified helical flow induced by the taper would lead to highly elevated wall shear stress, remarkably reduced oscillating shear index and relative residence time at both the grafts and the anastomosis of the host vessel. The present findings therefore indicated that the new helical graft with taper would significantly enhance the helical flow in the grafts and host vessel, which may reduce the possibility of thrombus formation in the graft and intimal hyperplasia in the host vessel and hence improve the graft patency. In addition, the concept of helical shape with taper may also be applied to design arterial stents and arteriovenous shunts to obtain better hemodynamic performance., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Intravascular stenting is one of the most commonly used treatments to restore the vascular lumen and flow conditions, while perioperative complications such as thrombosis and restenosis are still nagging for patients. As the catheter with crimped stent and folded balloon is directly advanced through coronary artery during surgery, it is destined to cause interference as well as obstructive effect on blood flow. We wonder how the hemodynamic environment would be disturbed and weather these disturbances cause susceptible factors for those complications. Therefore, a realistic three-dimensional model of left coronary artery was reconstructed and blood flow patterns were numerically simulated at seven different stages in the catheter insertion process. The results revealed that the wall shear stress (WSS) and velocity in left anterior descending (LAD) were both significantly increased after catheter inserted into LAD. Besides, the WSS on the catheter, especially at the ending of the catheter, was also at high level. Compared with the condition before catheter inserted, the endothelial cells of LAD was exposed to high-WSS condition and the risk of platelet aggregation in blood flow was increased. These influences may make coronary arteries more vulnerable for perioperative complications., (Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.)

Local flow disturbance by arterial stent struts has been shown to play an important role in stent thrombosis. To reduce the local flow disturbance near a stent strut, we proposed a new concept of stent design with small holes in the stent struts. The present study evaluated the new design numerically by comparing it with the traditional stent in terms of local hemodynamic parameters such as flow velocity, flow recirculation area, time-averaged wall shear stress (TAWSS), oscillating shear index (OSI), and relative residence time (RRT). The results demonstrated that when compared with the traditional strut, the new design could significantly enhance flow velocity and reduce the flow recirculation zone in the vicinity of the strut. Moreover, the new design would significantly elevate TAWSS and remarkably reduce OSI and RRT along the host arterial wall. In conclusion, the new design of stent struts with punched holes is advantageous over the traditional one in the aspect of improving local hemodynamics, which may reduce thrombosis formation and promote re-endothelialization after stenting., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

The aim of this study was to investigate the drug distribution in arteries treated with DES-BMS stenting strategy and to analyze the influence of proximal DES on distal segments of BMS. A straight artery model (Straight Model) and a branching artery model (Branching Model) were constructed in this study. In each model, the DES was implanted at the proximal position and the BMS was implanted distally. Hemodynamic environments, drug delivery and distribution features were simulated and analyzed in each model. The results showed that blood flow would contribute to non-uniform drug distribution in arteries. In the Straight Model the proximal DES would cause drug concentration in BMS segments. While in the Branching Model the DES in the main artery has slight influence on the BMS segments in the branch artery. In conclusion, due to the blood flow washing effect the uniformly released drug from DES would distribute focally and distally. The proximal DES would have greater influence on the distal BMS in straight artery than that in branching artery. This preliminary study would provide good reference for atherosclerosis treatment, especially for some complex cases, like coronary branching stenting., (Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.)

Clinical trials have shown overlapping bare-metal stents provoke effective thrombus clot within the aneurysm sac and shrinkage of the aneurysm by directly regulating the hemodynamics. To gain insight into the hemodynamic mechanism of the technique, three cases of simplified thoracic aortic aneurysm models (with no stent, a single stent and two overlapped stents deployed within the aneurysm sac) were studied and compared in terms of time-varying velocity and shear rate, time-averaged wall shear stress (TAWSS), oscillating shear index (OSI) and relative residence time (RRT). The results demonstrated that the overlapping stents' strategy was more effective in reducing the velocity of blood flow within the aneurysm, especially for the area near the aneurysm wall. Stenting induced a dramatic change trend of shear rate during the cardiac cycle, in which a very high shear rate (>10,000 s(-1)) during the systole and a quite low shear rate (<1000 s(-1)) during the diastole were observed, respectively. Moreover, reduced TAWSS and OSI and elevated RRT values were observed on the aneurysm wall after stent placement. The effects of stenting on the shear rate, TAWSS, OSI and RRT in the aneurysm would be significantly enhanced by two overlapped stents. The present findings therefore indicated that, the overlapping bare-metal stents can isolate the aneurysm effectively and may create a favorable hemodynamic environment provoking platelets activation and aggregation within the aneurysm, which may promote thrombus formation/growth there, hence contribute to degradation of the aneurysm., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Renal artery stenosis (RAS) and renal complications emerge in some patients after endovascular aneurysm repair (EVAR) to treat abdominal aorta aneurysm (AAA). The mechanisms for the causes of these problems are not clear. We hypothesized that for EVAR patients, lower limb exercise could negatively influence the physiology of the renal artery and the renal function, by decreasing the blood flow velocity and changing the hemodynamics in the renal arteries. To evaluate this hypothesis, pre- and post-operative models of the abdominal aorta were reconstructed based on CT images. The hemodynamic environment was numerically simulated under rest and lower limb exercise conditions. The results revealed that in the renal arteries, lower limb exercise decreased the wall shear stress (WSS), increased the oscillatory shear index (OSI) and increased the relative residence time (RRT). EVAR further enhanced these effects. Because these parameters are related to artery stenosis and atherosclerosis, this preliminary study concluded that lower limb exercise may increase the potential risk of inducing renal artery stenosis and renal complications for AAA patients. This finding could help elucidate the mechanism of renal artery stenosis and renal complications after EVAR and warn us to reconsider the management and nursing care of AAA patients.