Effect of veno-arterial extracorporeal membrane oxygenation lower-extremity cannulation on intra-arterial flow characteristics, oxygen content, and thrombosis risk.

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.

Analysis of non-physiological shear stress-induced red blood cell trauma across different clinical support conditions of the blood pump.

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.

The Impact of Rotor Axial Displacement Variation on Simulation Accuracy of Fully Magnetic Levitation Centrifugal Blood Pump.

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.

The impact of contrast retention on thrombus formation risks in patients with atrial fibrillation: A numerical study.

Background: Contrast retention (CR) is an important predictor of left atrial appendage thrombus (LAAT) and stroke in patients with non-valvular atrial fibrillation (AF). We sought to explore the underlying mechanisms of CR using computational fluid dynamic (CFD) simulations. Methods: A total of 12 patients with AF who underwent both cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) before left atrial appendage occlusion (LAAO) were included in the study. The patients were allocated into the CR group or non-CR group based on left atrial appendage (LAA) angiography. Patient-specific models were reconstructed to evaluate time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and endothelial cell activation potential (ECAP). Additionally, the incidence of thrombosis was predicted using residence time (RT) at different time-points. Results: TAWSS was lower [median (Interquartile Range) 0.27 (0.19-0.47) vs 1.35 (0.92-1.79), p < 0.001] in LAA compared to left atrium. In contrast, RRT [1438 (409.70-13869) vs 2.23 (1.81-3.14), p < 0.001] and ECAP [122.70 (30.01-625.70) vs 0.19 (0.16-0.27), p < 0.001)] was higher in the LAA. The patients in the CR group had significantly higher RRT [(mean ± SD) 16274 ± 11797 vs 639.70 ± 595.20, p = 0.009] and ECAP [610.80 ± 365.30 vs 54.26 ± 54.38, p = 0.004] in the LAA compared to the non-CR group. Additionally, patients with CR had a wider range of thrombus-prone regions [0.44(0.27-0.66)% vs 0.05(0.03-0.27)%, p = 0.009] at the end of the 15th cardiac cycle. Conclusions: These findings suggest that CR might be an indicator of high-risk thrombus formation in the LAA. And CT-based CFD simulation may be a feasible substitute for the evaluation of LAA thrombotic risk in patients with AF, especially in patients with CR.

Development and validation of a mathematical model for evaluating shear-induced damage of von Willebrand factor.

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 r2 > 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.

A mathematical model for assessing shear induced bleeding risk.

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.

The impact of rotor configurations on hemodynamic features, hemocompatibility and dynamic balance of the centrifugal blood pump: A numerical study.

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.

Impact of volute design features on hemodynamic performance and hemocompatibility of centrifugal blood pumps used in ECMO.

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.

Multi-indicator analysis of mechanical blood damage with five clinical ventricular assist devices.

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.

Morphometric and Hemodynamic Analysis of the Compressed Iliac Vein.

PURPOSE: To investigate the relationship between the morphological structure and hemodynamic properties of the compressed iliac vein and explore the reason for the formation of thrombosis in the compressed iliac vein. MATERIALS AND METHODS: A total of 11 patients with iliac vein compression syndrome (IVCS) were included in this study, and their iliac veins were reconstructed in 3 dimensions (3D). The morphological structures of the iliac veins (confluence angle, degree of stenosis) were analyzed based on the 3D model. Variations in the hemodynamic properties of the iliac vein were investigated at 4 typical moments in one cardiac cycle, and the relationship between the different morphological configurations and the pressure difference was investigated. RESULTS: In the region of the compressed iliac vein, the blood flow velocity is accelerated and the pressure changes abruptly accompanied by the increase in pressure difference. Higher time averaged wall shear stress (TAWSS) and lower relative residence time (RRT) appeared in stenosis regions of compressed iliac vein, while TAWSS was low and RRT was large near the stenosis position. There was a strong positive correlation between the degree of stenosis and the pressure difference (r=0.894), and a positive correlation between the confluence angle of the iliac vein and the pressure difference (r=0.638). CONCLUSION: The morphological structure of the compressed iliac vein has an obvious influence on the hemodynamic surroundings; the pressure difference becomes larger when the degree of stenosis and the confluence angle increase. The iliac vein luminal areas with low TAWSS and high RRT near the compressed location can impede blood flow and lead to accumulation of blood components, which may increase the risk of thrombosis formation and should be fully considered in the treatment of IVCS.

The Impact of a New Arterial Intravascular Pump on Aorta Hemodynamic Surrounding: A Numerical Study.

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.

A New Mathematical Numerical Model to Evaluate the Risk of Thrombosis in Three Clinical Ventricular Assist Devices.

(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.

Investigation of the influence of blade configuration on the hemodynamic performance and blood damage of the centrifugal blood pump.

PURPOSE: The design and optimization of centrifugal blood pumps are crucial for improved extracorporeal membrane oxygenation system performance. Secondary flow passages are common in centrifugal blood pumps, allowing for a high volume of unstable flow. Traditional design theory offers minimal guidance on the design and optimization of centrifugal blood pumps, so it's critical to understand how design parameter variables affect hydraulic performance and hemocompatibility. METHODS: Computational fluid dynamics (CFD) was employed to investigate the effects of blade number, blade wrap angle, blade thickness, and splitters on pressure head, hemolysis, and platelet activation state. Eulerian and Lagrangian features were used to analyze the flow fields and hemocompatibility metrics such as scalar shear stress, velocity distribution, and their correlation. RESULTS: The equalization of frictional and flow losses allow impellers with more blades and smaller wrap angles to have higher pressure heads, whereas the trade-off between the volume of high scalar shear stress and exposure time allows impellers with fewer blades and larger blade wrap angles to have a lower HI; there are configurations that increase the possibility of platelet activation for both number of blades and wrap angles. The hydraulic performance and hemocompatibility of centrifugal blood pumps are not affected by blade thickness. Compared to the main blades, splitters can improve the blood compatibility of a centrifugal blood pump with a small reduction in pressure head, but there is a trade-off between the length and location of the splitter that suppresses flow losses while reducing the velocity gradient. According to correlation analysis, pressure head, HI, and the volume of high shear stress were all substantially connected, and exposure time had a significant impact on HI. The platelet activation state was influenced by the average scalar shear stress and the volume of low velocity. CONCLUSION: The findings reveal the impact of design variables on the performance of centrifugal blood pumps with secondary flow passages, as well as the relationship between hemocompatibility, hydraulic performance, and flow characteristics, and are useful for the design and optimization of this type of blood pump, as well as the prediction of clinical complications.

VAMP3 and SNAP23 as Potential Targets for Preventing the Disturbed Flow-Accelerated Thrombus Formation.

Disturbed blood flow has been recognized to promote platelet aggregation and thrombosis via increasing accumulation of von Willebrand factor (VWF) at the arterial post-stenotic sites. The mechanism underlying the disturbed-flow regulated endothelial VWF production remains elusive. Here we described a mouse model, in which the left external carotid artery (LECA) is ligated to generate disturbed flow in the common carotid artery. Ligation of LECA increased VWF accumulation in the plasma. Carotid arterial thrombosis was induced by ferric chloride (FeCl3) application and the time to occlusion in the ligated vessels was reduced in comparison with the unligated vessels. In vitro, endothelial cells were subjected to oscillatory shear (OS, 0.5 ± 4 dynes/cm2) or pulsatile shear (PS, 12 ± 4 dynes/cm2). OS promoted VWF secretion as well as the cell conditioned media-induced platelet aggregation by regulating the intracellular localization of vesicle-associated membrane protein 3 (VAMP3) and synaptosomal-associated protein 23 (SNAP23). Disruption of vimentin intermediate filaments abolished the OS-induced translocation of SNAP23 to the cell membrane. Knockdown of VAMP3 and SNAP23 reduced the endothelial secretion of VWF. Systemic inhibition of VAMP3 and SNAP23 by treatment of mice with rapamycin significantly ameliorated the FeCl3-induced thrombogenesis, whereas intraluminal overexpression of VAMP3 and SNAP23 aggravated it. Our findings demonstrate VAMP3 and SNAP23 as potential targets for preventing the disturbed flow-accelerated thrombus formation.

[Biomechanical research progress on sex differences of abdominal aortic aneurysm].

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.

Sustained release and enhanced bioavailability of injectable scutellarin-loaded bovine serum albumin nanoparticles.

The aim of this study is to characterize the in-vitro physicochemical and in-vivo pharmacokinetic properties of the scutellarin-loaded bovine serum albumin nanoparticles (STA-BSA-NPs). STA existed as amorphous form in the nanoparticles. Reconstituted STA-BSA-NPs had an average particle size of 283.4 nm and a zeta potential of +17.95 mV. The in-vitro sustained release profile was well fitted with Weibull distribution model. In comparison to STA solution, STA-BSA-NPs exhibited a significantly higher plasma concentration from 20 min to 6 h after intravenous administration to rats. In addition, significantly higher AUC(0-inf) (2.8-fold), prolonged elimination half-life (4.2-fold) and lower clearance (2.7-fold) were achieved.