Stenotic Region Research Articles

Fractional flow reserve-based 4D hemodynamic simulation of time-resolved blood flow in left anterior descending coronary artery

BackgroundThe purpose of this study was to investigate the feasibility of the non-invasive assessment of hemodynamic parameters with computational fluid dynamics in left anterior descending coronary artery based on invasive fractional flow reserve. MethodsA left coronary artery model based on computed tomography angiography was reconstructed using MIMICS 18.0 for computational fluid dynamics analysis. With actual fractional flow reserve measured from the patient, 4D hemodynamic profiles of time-resolved blood flow were simulated. FindingsThe 4D blood flow simulation could provide extensive information of blood flow status. Hemodynamic parameters, such as velocity, wall shear stress and pressure were simulated throughout the cardiac cycle. There might be high flow velocities and high wall shear stress in the stenotic region throughout the whole cycle, both of which peaked in the case of the maximum inlet differential pressure. The reverse flow and vortex were detectable at the downstream areas beneath the stenotic site. The pressure remarkably increased near the proximal stenotic end and declined in the mid-stenosis. Moreover, the simulation results provided detailed and accurate mass flow measurements of hemodynamic parameters as well. InterpretationThe computational fluid dynamics analysis of 4D blood flow based on fractional flow reserve is feasible in left anterior descending coronary artery. It presents the merits of providing both qualitative and quantitative information for further investigation of the links between hemodynamic parameters and left anterior descending artery stenosis.

Geometric determinants of local hemodynamics in severe carotid artery stenosis

In cases of severe carotid artery stenosis (CAS), carotid endarterectomy (CEA) is performed to recover lumen patency and alleviate stroke risk. Under current guidelines, the decision to surgically intervene relies primarily on the percent loss of native arterial lumen diameter within the stenotic region (i.e. the degree of stenosis). An underlying premise is that the degree of stenosis modulates flow-induced wall shear stress elevations at the lesion site, and thus indicates plaque rupture potential and stroke risk. Here, we conduct a retrospective study on pre-CEA computed tomography angiography (CTA) images from 50 patients with severe internal CAS (>60% stenosis) to better understand the influence of plaque and local vessel geometry on local hemodynamics, with geometrical descriptors that extend beyond the degree of stenosis. We first processed CTA images to define a set of multipoint geometric metrics characterizing the stenosed region, and next performed computational fluid dynamics simulations to quantify local wall shear stress and associated hemodynamic metrics. Correlation and regression analyses were used to relate obtained geometric and hemodynamic metrics, with inclusion of patient sub-classification based on the degree of stenosis. Our results suggest that in the context of severe CAS, prediction of shear stress-based metrics can be enhanced by consideration of readily available, multipoint geometric metrics in addition to the degree of stenosis.

The Flow Dependent Adhesion of von Willebrand Factor (VWF)-A1 Functionalized Nanoparticles in an in Vitro Coronary Stenosis Model.

In arterial thrombosis, von Willebrand factor (VWF) bridges platelets to sites of vascular injury. The adhesive properties of VWF are controlled by its different domains, which may be engineered into ligands for targeting nanoparticles to vascular injuries. Here, we functionalized 200 nm polystyrene nanoparticles with the VWF-A1 domain and studied their spatial adhesion to collagen or collagen-VWF coated, real-sized coronary stenosis models under physiological flow. When VWF-A1 nano-particles (A1-NPs) were perfused through a 75% stenosis model coated with collagen-VWF, the particles preferentially adhered at the post stenotic region relative to the pre-stenosis region while much less adhesion was detected at the stenosis neck (~ 65-fold less). When infused through collagen-coated models or when the A1 coating density of nanoparticles was reduced by 100-fold, the enhanced adhesion at the post-stenotic site was abolished. In a 60% stenosis model, the adhesion of A1-NPs to collagen-VWF-coated models depended on the location examined within the stenosis. Altogether, our results indicate that VWF-A1 NPs exhibit a flow-structure dependent adhesion to VWF and illustrate the important role of studying cardiovascular nano-medicines in settings that closely model the size, geometry, and hemodynamics of pathological environments.

Hybrid mediated blood flow investigation for atherosclerotic bifurcated lesions with slip, convective and compliant wall impacts

ObjectiveThe present investigation is concerned with hybrid mediated blood flow model through atherosclerotic bifurcated artery with slip effects by considering the properties of compliant walls. Design/approachIn human body, the circulatory system is made up of a network of blood vessels that include the bifurcation therefore the influence of hybrid nanoparticles on parent artery with mild stenosis, at apex and in the region of daughter arteries (after being bifurcated) is observed. Blood streaming along the segment of vessel is considered to be Newtonian. The compliant nature of the atherosclerotic artery wall is also considered to create association with permeability aspects for the thickness of arterial wall. Property of heat transfer with convective impacts is taken into account to weaken the stenotic lesions. Through phase flow model approach, a mathematical model is develop with the phenomena of hybrid nanofluid. FindingsFor theoretical research of designed equations experimentally determined values of nanoparticles and base fluid are used. Further, flow configurations of hemodynamics are figure out to analyze the blood flow through bifurcated stenotic artery. The comparison in parent and daughter artery is plotted for velocity profile. These patterns provide us a graphical way to recognize the importance of theoretical assistance of this model to biomedical field. At the end, it is concluded from graphical results that slip to the boundary reduces the resistance to flow for atherosclerotic bifurcated artery. ConclusionsIn bifurcated artery, blood circulation is assumed due to difference of pressure between atherosclerotic and non-atherosclerotic portions. Slip impacts are more effective to reduce the hemodynamics effects of stenosis for bifurcated artery. Bifurcation angle reduces the shear stress for daughter artery whereas opposite behavior is observed for parent artery. Compliant wall parameters reduces the inner bolus size in stenotic region while number of bolus increases in bifurcated region. Reduction in the amplitude of shear stress for convective parameter is more prominent in the parent artery as compared to daughter artery.

Geometrical effects in the hemodynamics of stenotic and non-stenotic left coronary arteries-numerical and in vitro approaches.

Atherosclerosis is a common cardiovascular disease found in the left coronary artery (LCA), closely linked to local hemodynamic, which, in turn, is highly influenced by the artery geometry. The hemodynamics in the LCA was studied in a patient-specific geometry without any sign of disease using both numerical and in vitro approaches. The influence of non-planarity was evaluated through two models of the patient-specific LCA that deviate from its original geometry in their planarity. Afterwards, in all models, irregular stenoses were created by a procedure in which the stenosis emerges by diffusion from low wall shear stress (WSS) areas. The WSS distribution and flow patterns were evaluated in all the models. The experimental results validate the numerical code developed to study the blood flow assuming a steady state Newtonian behavior. Comparison between the planar and non-planar idealized LCA revealed no significant differences in low WSS regions forming stenotic regions with identical shape. In the patient-specific LCA, the low WSS regions are not consistent with the idealized models leading to a different stenosis shape. The results revealed that the non-planarity has an unquestionable effect in helicity. It was also demonstrated that eccentricity of the vessels cross section and the position of the apex in relation to the axis of the parent branch contribute to the flow patterns observed. Numerical results of pulsatile blood flow assuming a non-Newtonian behavior, in the patient-specific LCA, reinforce the non-planarity effect in local hemodynamics.

Wave propagation in stenotic vessels; theoretical analysis and comparison between 3D and 1D fluid–structure-interaction models

Using analytical expressions for the pressure and velocity waveforms in tapered vessels, we construct a linear 1D model for wave propagation in stenotic vessels in the frequency domain. We demonstrate that using only two parameters to approximate the exact geometry of the constriction (length and degree of stenosis), we can construct a model that can be solved analytically and can approximate with excellent accuracy the response of the original vessel for a wide range of physiologically relevant frequencies. We then proceed to compare the 1D results with full 3D FSI results from the literature for parameters corresponding to an idealized stenotic carotid artery. We find excellent matching with the volume flow rare over the cardiac cycle (less than 1% error). Using results from DNS simulations to parametrize the velocity profile in the stenotic region, we manage to predict also the pressure distribution with small error (a few percentage points). The method proposed in the paper can be used to approximate vessels of arbitrary shape profile and can be extended to cover the whole cardiovascular tree. Recursive expressions make the solution very fast and open the possibility of carrying out sensitivity and uncertainty quantification studies that require thousands (or even millions) of simulations with minimal cost.

A hemodynamic model with a seepage condition and fluid-structure interactions for blood flow in arteries with symmetric stenosis.

To strengthen the detailed understanding of arterial stenosis, we construct a novel hemodynamic model. Frequently used symmetric stenosis is employed in this work. Being different from a traditional model, this numerical model adopts microcirculation resistance as an outlet boundary condition, which is called a seepage condition. Meanwhile, fluid-structure interactions are used in the numerical simulation considering the interrelationship of blood and arterial wall. Our results indicate that (i) the region upstream of stenosis experiences very high pressures during cardiac cycles, (ii) pressure drops much faster as the flow moves into the stenotic region, and (iii) high flow velocities and high shear stresses occur in the post-stenosis region. This work provides evidence that there is a strong effect of the function of microcirculation on stenosis. This contributes to evaluating potential stenotic behavior in arteries and is pivotal in guiding disease treatment.

Downstream platelet adhesion and activation under highly elevated upstream shear forces

Elevated shear force caused by an anastomotic stenosis is a common complication at the blood vessel-vascular implant interface. Although elevated shear forces were found to cause platelet aggregation around a stenotic region, transient platelet exposure to elevated shear forces and subsequent downstream events occurring under lower shear force were not extensively studied. We hypothesize that effects of elevated shear forces on pre-activation of platelets for downstream adhesion and activation are relevant in understanding the increased thrombotic risk associated with blood-contacting devices. We designed a microfluidic flow system to mimic the hemodynamic environment of vasculature with an upstream anastomotic stenosis with five wall shear strain rates ranging from 1620 s−1 to 11560 s−1. Under shear flow conditions, transient exposure of whole blood to elevated shear forces resulted in higher downstream platelet adhesion onto three different immobilized platelet agonists: fibrinogen, collagen, or von Willebrand factor. Platelet expression of four activation markers (P-selectin, GPIIb/IIIa, lysosomal glycoprotein, and phosphatidylserine) significantly increased after transient exposure to higher upstream wall shear strain rates of 2975–11560 s−1. A significant lysis was observed when platelets were primed by upstream wall shear strain rate of 11560 s−1. These experimental results could be helpful to understand how altered hemodynamics around an anastomotic stenosis promotes thrombus formation downstream. Statement of SignificanceStudying the downstream response of platelets following transient exposure to an upstream agonist is important because of significant clinical implications to the implantation of vascular devices. Due to intimal fibrous hyperplasia, vascular biomaterials such as synthetic small-diameter vascular grafts sometimes become stenotic (narrow), leading to transient platelet exposure to elevated shear forces. In this study, a microfluidic flow system was developed to mimic a stenosed vascular graft and to investigate how highly elevated, transient upstream shear forces, typically found in severe stenosis, results in the pre-activation of platelets for downstream adhesion and activation. The findings of the present study have implications for optimizing the design of blood-contacting biomaterials in order to minimize thrombotic risk associated with transiently elevated shear forces. The findings also provide additional insights into the mechanisms of thrombus formation at the post-stenotic regions of vascular implants.

An investigation of the detection capability of pulsed wave duplex Doppler of low grade stenosis using ultrasound contrast agent microbubbles – An in-vitro study

ObjectiveThe objective of the study was to investigate whether clinically used ultrasonic contrast agents improved the accuracy of spectral Doppler ultrasound in the detection of low grade (<50%) renal artery stenosis. Low grade stenoses in the renal artery are notoriously difficult to reliably detect using Doppler ultrasound due to difficulties such as overlying fat and bowel gas. MethodsA range of anatomically-realistic renal artery phantoms with varying low degrees of stenosis (0, 30 and 50%) were constructed and peak velocity data was measured from within the pre-stenotic and mid-stenotic regions in each phantom, for both unenhanced and contrast-enhanced spectral Doppler data acquisitions. The effect of a 20 mm overlying fat layer on the ultrasound beam distortion and phase aberration, and hence on the measured peak velocity data, was also investigated. ResultsThe overlying fat layer produced a statistically significant underestimation (p < 0.01) in both the peak velocity and peak velocity ratio [Stenotic Region(Vmax)/Pre-stenotic Region(Vmax)] for the 0% and 30% stenosis models, but not the 50% model. A statistically significant increase (p < 0.01) in the peak velocity was found in the contrast-enhanced Doppler spectra; however, no significant difference was found between the unenhanced and contrast enhanced peak velocity ratio data, which suggests that the ratio metric has better diagnostic accuracy. The peak velocity ratios determined for each of the contrast-enhanced phantoms correctly predicted if the phantom had a stenosis and furthermore correctly classified the degree of stenosis. ConclusionContrast-enhanced Doppler ultrasound could significantly assist in the early detection of renal artery disease.

Our eight years experience in postintubation/posttracheostomy tracheal stenosis.

The most common cause of tracheal stenosis (TS) continues to be traumas according to the intubation and tracheostomy. Bronchoscopy is considered the gold standard for the detection and diagnosis of tracheobronchial pathology. There are several treatment options. We aimed to discuss our tracheal stenosis patients' treatment options, and their follow-up period. Consecutive referred patients between 2009 and 2018 presenting with TS were reviewed for the study. Demographic characteristics, localization, length and degree of stenosis, treatment techniques, postoperative complications, and survival were recorded for all patients. A total of 110 patients included. The mean age was 53.7 ± 16.7 (16-98 years) years. Of 110 patients, 54 (49.1%) were female. Most common type of stenosis was complex stenosis (74.5%). Mechanical dilatation was applied to all patients. Stenotic regions of 22 (20%) patients were cut with bronchoscopic scissor. Tracheal stents were inserted into trachea of 49 (44.5%) patients. During follow-up period; 36 of 110 (32.7%) patients had surgical resection. Six of 36 (16.7%) patients died during follow-up period (one of them died during surgery), 17 (47.2%) patients had total recovery after surgery. Thirteen of 36 (36.1%) patients had restenosis after surgery. Tracheal stenosis is a process seen after postintubation or posttracheostomy frequently and it has a wide range of management modalities. Although, it is believed that surgery is the most efficient technique in cases without medical contraindications, we determined that endoscopic interventions can be alternative therapeutic options for inoperable patients. Patients must be followed-up after interventional therapies because complications, and restenosis can usually be seen.

Evaluation of cerebrovascular reserve in patients with cerebrovascular diseases using resting-state MRI: A feasibility study

PurposeTo demonstrate the feasibility of mapping cerebrovascular reactivity (CVR) using resting-state functional MRI (fMRI) data without gas or other challenges in patients with cerebrovascular diseases and to show that brain regions affected by the diseases have diminished vascular reactivity. Materials and methodsTwo sub-studies were performed on patients with stroke and Moyamoya disease. In Study 1, 20 stroke patients (56.3 ± 9.7 years, 7 females) were enrolled and resting-state blood‑oxygenation-level-dependent (rs-BOLD) fMRI data were collected, from which CVR maps were computed. CVR values were compared across lesion, perilesional and control ROIs defined on anatomic images. Reproducibility of the CVR measurement was tested in 6 patients with follow-up scans. In Study 2, rs-BOLD fMRI and dynamic susceptibility contrast (DSC) MRI scans were collected in 5 patients with Moyamoya disease (32.4 ± 8.2 years, 4 females). Cerebral blood flow (CBF), cerebral blood volume (CBV), and time-to-peak (TTP) maps were obtained from the DSC MRI data. CVR values were compared between stenotic brain regions and control regions perfused by non-stenotic arteries. ResultsIn stroke patients, lesion CVR (0.250 ± 0.055 relative unit (r.u.)) was lower than control CVR (0.731 ± 0.088 r.u., p = 0.0002). CVR was also lower in the perilesional regions in a graded manner (perilesion 1 CVR = 0.422 ± 0.051 r.u., perilesion 2 CVR = 0.492 ± 0.046 r.u.), relative to that in the control regions (p = 0.005 and 0.036, respectively). In the repeatability analysis, a strong correlation was observed between lesion CVR (r2 = 0.91, p = 0.006) measured at two time points, as well as between control CVR (r2 = 0.79, p = 0.036) at two time points. In Moyamoya patients, CVR in the perfusion deficit regions delineated by DSC TTP maps (0.178 ± 0.189 r.u.) was lower than that in the control regions (0.868 ± 0.214 r.u., p = 0.013). Furthermore, the extent of reduction in CVR was significantly correlated with the extent of lengthening in TTP (r2 = 0.91, p = 0.033). ConclusionOur findings suggested that rs-BOLD data can be used to reproducibly evaluate CVR in patients with cerebrovascular diseases without the use of any vasoactive challenges.

Impact of temperature and concentration dispersion on the physiology of blood nanofluid: links to atherosclerosis

A theoretical model of blood-silver nanofluid flow through an \(\omega \)-shaped tapered stenotic artery in the presence of a catheter is understood in detail. The rheology of the blood is considered as that of a micro-polar fluid. Suspension of the silver nano-particles in the micro-polar fluid is proposed to investigate the temperature and concentration dispersion from the immersed temperature-sensitive drug-coated nano-particles. The effects of velocity discontinuity at the arterial wall in the stenotic and non-stenotic regions are considered. The outer surface of the catheter is layered with the temperature-sensitive, drug-coated nano-particles. The resulting mathematical formulation involving the coupled non-linear momentum, temperature and concentration equations is solved using the Homotopy Perturbation Method. The efficiency and convergence of the method to the modelled equations are discussed in detail. The consequent effects of the fluid and geometric parameters on pressure drop, flow rate, impedance and wall shear stress of the fluid flow are computed. It is noticed that the high volume fraction of the nano-particles in the blood results in high flow velocity, contributing to secondary flow regions, thus resulting in higher shear stress. Such high volume fraction of the nano-particle may lead to the pathological disorder called aneurysm. This physical model has an important application of drug delivery in biomedical and pharmaceutical industry to prevent obstructions in arteries. Further, the results obtained could be very useful in the manufacturing of related artificial devices.

DUAL- FREQUENCY FOCUSED ULTRASOUND- MEDIATED THROMBOLYTIC THERAPY ACCOMPANIED BY TISSUE PLASMINOGEN ACTIVATOR ADMINISTRATION REDUCE THROMBUS CONTENT IN THE ARTERIAL ATHEROTHROMBOTIC STENOSIS

Vascular disease arises through the complications of atherosclerosis, a complex chronic inflammatory condition affecting the arterial circulation. It leads to the development of vascular lesions or atherosclerotic plaques, which manifest as asymmetrical thickenings of the intima of medium to large sized elastic and muscular arteries. A plaque may rupture with high risk of subsequent thrombus mediated acute clinical events such as myocardial infarction and stroke. Focused ultrasound is one of the non- invasive methods to treat abnormal tissues. In pulsed- focused ultrasound with low duty cycle, which is used for thrombolysis, energy deposition rates are low that temperature rises are well below the threshold for thermal damage. The aim of this study was to generate a rabbit model of common carotid artery atherothrombotic stenosis and the subsequent investigating the feasibility of dual- frequency focused ultrasound - mediated thrombolytic therapy accompanied by tissue plasminogen activator (tPA) administration in this model. Briefly, New Zealand white rabbits were submitted to common carotid artery atherothrombotic stenosis by primary balloon injury followed 1.5% cholesterol- rich diet injury for 12 weeks and finally perivascular severe cold injury. Then treatment group underwent dual- frequency focused ultrasound (I= 3w, F= 3MHz, PD= 30 ms and I= 30 W/cm2, F= 150 KHz, PD= 150 ms) - mediated thrombolytic therapy accompanied by tPA (0.6 mg/kg) administration. Results from histopathology, B-mode and color Doppler ultrasonography, showed a significant reduction in the mean value for thrombus content, blood mean velocity and a significant increase in the mean value for blood volume flow at the stenotic region in the treatment group compared with the other groups (P<0.05). Focal thrombus disruption mechanism was partly clarified as originated from microjet formation upon bubble collapse. Enhanced anti- thrombotic effect of tPA, due to microjets- induced by dual- frequency focused ultrasound, can cause to reduce the thrombus content and significantly dilate the luminal cross-sectional area of stenosis and lower treatment time in comparison with conventional tPA thrombolytic therapy.

DEVELOPING OF A NEW RABBIT CAROTID ARTERY MODEL OF NEOINTIMAL HYPERPLASIA WITH SEVERE STENOSIS: MONITORED BY ULTRASONOGRAPHY AND HISTOPATHOLOGY

Neointimal hyperplasia is the major cause of restenosis after percutaneous coronary and carotid interventions such as stenting or angioplasty. Neointimal hyperplasia is also used to describe the thickening of venous and prosthetic bypass grafts that leads to reduced lumen diameter and flow and, ultimately, graft occlusion and thrombosis. Direct investigation of neointimal hyperplasia stenosis in human arteries is by nature difficult to do. As a result, animal models offer an alternative that can replicate the physiopathology aspects of neointimal hyperplasia stenosis while allowing for controllable variables and statistical data in a short period of time. Therefore, an appropriate animal model could prove critical to the research and development of new diagnostic and therapeutic modalities. The aim of this study was to generate an easily reproducible and inexpensive experimental rabbit common carotid artery of neointimal hyperplasia stenosis with morphological similarities to the human disease. Twenty- eight healthy male New Zealand white rabbits weighing 2.5-3.0 kg were used in this study. Rabbits were divided randomly into a healthy group (A) in which the rabbits consumed a standard chow diet (n = 14), and an injured group (B) in which the rabbits underwent perivascular cold injury to the right common carotid artery using liquid nitrogen. Histopathology results showed progressive smooth muscle cells proliferation in intimal layer, resulting in vessel wall thickening and the formation of neointimal hyperplasia with moderate artery stenosis in all of the rabbits’ arteries after four weeks. Results from color Doppler ultrasonography at the stenotic region showed a significant increase in the mean value for blood mean velocity, wall mean thickness, percentage of luminal cross- sectional area of stenosis and significant reduction in the mean value for blood volume flow in the neointimal hyperplasia group compared with the control group (p < 0.05). In conclusion, we successfully produced an easily reproducible and inexpensive experimental rabbit common carotid artery model of neointimal hyperplasia stenosis, which is similar to the condition seen in patients. This condition in rabbits can be properly assessed by color Doppler ultrasonography.

Daikenchuto (Da-Jian-Zhong-Tang) ameliorates intestinal fibrosis by activating myofibroblast transient receptor potential ankyrin 1 channel.

AIMTo investigate the anti-fibrotic effects of the traditional oriental herbal medicine Daikenchuto (DKT) associated with transient receptor potential ankyrin 1 (TRPA1) channels in intestinal myofibroblasts.METHODSInflammatory and fibrotic changes were detected in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) chronic colitis model of wild-type and TRPA1-knockout (TRPA1-KO) mice via pathological staining and immunoblotting analysis. Ca2+ imaging experiments examined the effects of DKT and its components/ingredients on intestinal myofibroblast (InMyoFib) cell TRPA1 channel function. Pro-fibrotic factors and transforming growth factor (TGF)-β1-associated signaling were tested in an InMyoFib cell line by qPCR and immunoblotting experiments. Samples from non-stenotic and stenotic regions of the intestines of patients with Crohn’s disease (CD) were used for pathological analysis.RESULTSChronic treatment with TNBS caused more severe inflammation and fibrotic changes in TRPA1-KO than in wild-type mice. A one-week enema administration of DKT reduced fibrotic lesions in wild-type but not in TRPA1-KO mice. The active ingredients of DKT, i.e., hydroxy α-sanshool and 6-shogaol, induced Ca2+ influxes in InMyoFib, and this was antagonized by co-treatment with a selective TRPA1 channel blocker, HC-030031. DKT counteracted TGF-β1-induced expression of Type I collagen and α-smooth muscle actin (α-SMA), which were accompanied by a reduction in the phosphorylation of Smad-2 and p38-mitogen-activated protein kinase (p38-MAPK) and the expression of myocardin. Importantly, 24-h incubation with a DKT active component Japanese Pepper increased the mRNA and protein expression levels of TRPA1 in InMyoFibs, which in turn negatively regulated collagen synthesis. In the stenotic regions of the intestines of CD patients, TRPA1 expression was significantly enhanced.CONCLUSIONThe effects of DKT on the expression and activation of the TRPA1 channel could be advantageous for suppressing intestinal fibrosis, and benefit inflammatory bowel disease treatment.

Clinical Efficacy of Percutaneous Transhepatic Portal Vein Angioplasty for Late-onset Portal Vein Stenosis in Pediatric Liver Transplant Patients.

Stenosis of the portal vein (PV) is a rare complication after liver transplantation (LT) in pediatric patients, and it adversely affects outcomes. We reviewed the safety and efficacy of percutaneous transhepatic balloon angioplasty (PTBA) as a treatment for post-LT late-onset PV stenosis (PVS). Three hundred eighteen patients between the ages of 0 and 21 years received an LT from 2001 to 2016 at this tertiary center. Twenty-one children were evaluated for PVS using percutaneous portal venography. Of the 21, 19 patients (7 female, 12 male) with a median age of 12 years (7-15 years) were diagnosed with PVS and received PTBA. Two patients were excluded: one did not have PVS, and one received shunt surgery. Median time between LT and PTBA was 83 months (interquartile range, 49-138). For patients in whom pressure could be accurately measured (n = 9), mean PV pressure gradient was 6.3 mm Hg (SD, 5.0) preprocedure and 0.9 mm Hg (SD, 1.2) postprocedure. Mean percentage improvement in gradient across the stenotic region was 86.2% (SD, 15.9%; P < 0.01). At 12-month postprocedure, there was a mean improvement (pre-PTBA vs post-PTBA means) in bilirubin by 28.2% (0.6 mg/dL vs 0.4 mg/dL, P = 0.07), aspartate aminotransferase by 31.2% (116.3 IU/L vs 28.1 IU/L, P = 0.04), alanine aminotransferase by 40.7% (140.3 IU/L vs 28.6 IU/L, P = 0.07), γ-glutamyltransferase by 29.0% (337.2 IU/L vs 38.0 IU/L, P = 0.06) and platelets by 62.1% (128.3 vs 191.1 × 10/L, P = 0.03). The PV patency was successfully maintained in 18 of 19 patients for a median of 16 months (interquartile range, 5-35). One patient received a successful repeat procedure for restenosis at 6 weeks. Angioplasty for PVS after pediatric LT is a safe and effective treatment with good patency and improved clinical outcomes. Longer follow-up studies are required.

A numerical study on the effect of trapezium stenosis shape on the axisymmetric flow field around stenosis

Numerical simulations on the pulsatile flow in stenosed tubes were conducted to investigate the effect of trapezium shape of stenosis on the flow field around stenoses. Four trapezium shapes of stenoses were considered by varying contraction, plateau, and expansion parts of stenoses for different stenosis area reduction ratios. The Galerkin finite element method based on the P2P1 mixed element was employed to solve the axisymmetric incompressible Navier-Stokes equations and the continuity equation. The proposed numerical method was validated by solving a benchmark problem of stenotic flow. It was found that the average pressure profile along the centerline was more affected by the contraction shape than the expansion shape. It was also revealed that the average wall shear stress of mild contraction was greater than that of sudden contraction around the stenotic region. Furthermore, the pressure drop across the stenosis was found to be associated with the form drag experienced by the stenosis.

Pulsatile flow through a constricted tube: effect of stenosis morphology on hemodynamic parameters

In this paper, we investigate pulsatile flow through a constricted tube with the aim of assessing the effect of stenosis morphology on hemodynamic parameters. The fluid-solid interaction of pulsatile flow through a compliant tube with elastic walls was simulated using an arbitrary Lagrangian-Eulerian (ALE) finite-element method. We consider blood flow through various mild stenoses of 25.8% severity in diameter with trapezoidal and bell-like morphologies at a fixed Womersley number of 7.75. The results show that the distribution of the time-averaged wall shear stress (TAWSS), which is the main factor affecting the hemodynamic parameters, strongly depends on the axial stretch of the stenosis; elongation of the stenotic region increases by 41.1% the maximum TAWSS for stenoses of trapezoidal morphology whereas the maximum TAWSS decreases by 14.8% for the corresponding stenoses of bell-like morphology. The present findings indicate that risk factors due to atherosclerosis may vary in a complicated manner as an atheromatous plaque gradually builds up and morphs with time.

Effects of upstream shear forces on priming of platelets for downstream adhesion and activation

Platelets in flowing blood are sometimes exposed to elevated shear forces caused by anastomotic stenosis at the blood vessel-vascular implant interface. The objective of this study was to determine how effective upstream shear forces are in priming platelets for downstream adhesion and activation. Flow chambers with upstream stenotic regions (shear rates of 400–1000 s−1) were manufactured by relief molding of polydimethylsiloxane. Downstream from the stenotic regions, microcontact printing was used to covalently immobilize three different proteins (fibrinogen, collagen, or von Willebrand factor) to serve as platelet capture agents. Anticoagulated whole blood was perfused through the flow chambers and platelet adhesion to the downstream capture region was quantified. It was found that transient exposure of platelets to increased shear forces resulted in higher platelet adhesion on all three proteins. The duration of the platelet exposure to elevated shear forces was varied by changing the length of the stenotic regions. The results indicated that, in addition to the magnitude of shear forces, the duration of exposure to these forces was also an important factor in priming platelets. The effect of upstream shear forces on platelet activation was assessed by quantifying P-selectin, integrin αIIbβ3, lysosomal glycoprotein, and phosphatidylserine exposure using flow cytometry. The results suggested that increased shear forces were capable of increasing the priming of platelets for downstream activation. This study implicates the anastomotic region(s) of vascular implants as a locus of platelet pre-activation that may lead to thrombus formation downstream. Statement of SignificanceA synthetic small-diameter vascular graft can often become stenotic due to intimal fibrous hyperplasia, either generally along the inside of the graft or at the anastomotic regions, leading to an increased shear force on flowing platelets. Our lab is studying how the upstream platelet preactivation (aka “priming”) in flowing blood affects their downstream adhesion and activation. This manuscript describes a study in which priming of platelets is achieved by upstream stenotic narrowing in a microfluidic flow chamber. Such experimental design was intended to mimic a vascular implant with stenotic upstream anastomosis and downstream exposed platelet protein agonists. Understanding how the pre-activated platelets respond to imperfect vascular implant surfaces downstream is an important factor in designing better vascular implants.

Usefulness of acceleration time ratio in diagnosis of internal carotid artery origin stenosis

PurposeThe acceleration time (AcT) ratio of the internal carotid artery (ICA) is increased in ICA stenosis. However, there are few reports that have directly compared the AcT ratio to digital subtraction angiography (DSA) findings.MethodsWe evaluated 177 vessels with DSA and carotid artery ultrasonography. The AcT ratio was calculated as AcT of the ICA (ICA–AcT)/AcT of the ipsilateral common carotid artery (CCA). We evaluated the correlation of DSA–NASCET stenosis with the origin of the ICA or the peak systolic velocity (ICApsv) in the stenotic region, ICApsv/peak systolic velocity of the CCA (CCApsv), ICA–AcT, and AcT ratio. Sensitivity and specificity for stenosis ≥ 70% were calculated based on the ICApsv, ICApsv/CCApsv, ICA–AcT, and AcT ratio.ResultsUsing NASCET criteria, 34 vessels had 70% or greater stenosis. DSA–NASCET showed a significant positive correlation with ICApsv, ICApsv/CCApsv, ICA–AcT, and AcT ratio (p < 0.0001). When the cut-off value for ICApsv was set at 176 cm/s, ICApsv/CCApsv at 2.42, ICA–AcT at 0.095 s, and the AcT ratio at 1.35, the sensitivity was 97.1, 97.1, 82.4, and 97.1%, and the specificity was 94.4, 91.0, 83.2, and 83.2%, for DSA–NASCET ≥ 70%, respectively.ConclusionThe AcT ratio is a beneficial parameter for evaluating ICA stenosis as well as ICApsv and ICApsv/CCApsv.