Effects of Diffusion Coefficients and Struts Apposition Using Numerical Simulations for Drug Eluting Coronary Stents

2007 ◽  
Vol 129 (5) ◽  
pp. 733-742 ◽  
Author(s):  
Rosaire Mongrain ◽  
Isam Faik ◽  
Richard L. Leask ◽  
Josep Rodés-Cabau ◽  
Éric Larose ◽  
...  

In the context of drug eluting stent, we present two-dimensional numerical models of mass transport of the drug in the wall and in the lumen to study the effect of the drug diffusion coefficients in the three principal media (blood, vascular wall, and polymer coating treated as a three-compartment problem) and the impact of different strut apposition configurations (fully embedded, half embedded, and not embedded). The different conditions were analyzed in terms of their consequence on the drug concentration distribution in the arterial wall. We apply the concept of the therapeutic window to the targeted vascular wall region and derive simple metrics to assess the efficiency of the various stent configurations. Although most of the drug is dispersed in the lumen, variations in the blood flow rate within the physiological range of coronary blood flow and the diffusivity of the drug molecule in the blood were shown to have a negligible effect on the amount of drug in the wall. Our results reveal that the amount of drug cumulated in the wall depends essentially on the relative values of the diffusion coefficients in the polymer coating and in the wall. Concerning the strut apposition, it is shown that the fully embedded strut configuration would provide a better concentration distribution.

2012 ◽  
Vol 81 (2) ◽  
pp. 268-273 ◽  
Author(s):  
Giovanni Paolo Talarico ◽  
Francesco Burzotta ◽  
Carlo Trani ◽  
Antonella Tommasino ◽  
Giampaolo Niccoli ◽  
...  

2014 ◽  
Vol 7 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Michelle K Fitts ◽  
Daniel B Pike ◽  
Kasey Anderson ◽  
Yan-Ting Shiu

Surgically-created blood conduits used for chronic hemodialysis, including native arteriovenous fistulas (AVFs) and synthetic AV grafts (AVGs), are the lifeline for kidney failure patients. Unfortunately, each has its own limitations; AVFs often fail to mature to become useful for dialysis and AVGs often fail due to stenosis as a result of neointimal hyperplasia, which preferentially forms at the graft-venous anastomosis. No clinical therapies are currently available to significantly promote AVF maturation or prevent neointimal hyperplasia in AVGs. Central to devising strategies to solve these problems is a complete mechanistic understanding of the pathophysiological processes. The pathology of arteriovenous access problems is likely multi-factorial. This review focuses on the roles of fluid-wall shear stress (WSS) and endothelial cells (ECs). In arteriovenous access, shunting of arterial blood flow directly into the vein drastically alters the hemodynamics in the vein. These hemodynamic changes are likely major contributors to non-maturation of an AVF vein and/or formation of neointimal hyperplasia at the venous anastomosis of an AVG. ECs separate blood from other vascular wall cells and also influence the phenotype of these other cells. In arteriovenous access, the responses of ECs to aberrant WSS may subsequently lead to AVF non-maturation and/or AVG stenosis. This review provides an overview of the methods for characterizing blood flow and calculating WSS in arteriovenous access and discusses EC responses to arteriovenous hemodynamics. This review also discusses the role of WSS in the pathology of arteriovenous access, as well as confounding factors that modulate the impact of WSS.


Author(s):  
Wenzhu Li ◽  
Chase W. Kessinger ◽  
Makoto Orii ◽  
Hang Lee ◽  
Lang Wang ◽  
...  

Background: Up to 50% of patients with proximal deep venous thrombosis (DVT) will develop the post-thrombotic syndrome (PTS) characterized by limb swelling and discomfort, hyperpigmentation, skin ulcers, and impaired quality-of-life. While catheter-based interventions enabling restoration of blood flow (RBF) have demonstrated little benefit on PTS, the impact on the acuity of the thrombus and mechanisms underlying this finding remain obscure. Here in experimental and clinical studies, we examined whether RBF has a restricted time window for improving DVT resolution. Methods: First, experimental stasis DVT was generated in C57/BL6 mice (N=291) by inferior vena cava ligation. To promote RBF, mice underwent mechanical de-ligation with or without intravenous recombinant tissue plasminogen activator (rtPA), administered two days after de-ligation. RBF was assessed over time by ultrasonography and intravital microscopy. Resected thrombosed IVC specimens underwent thrombus and vein wall histological and gene expression assays. Next, in a clinical study, we conducted a post-hoc analysis of the ATTRACT pharmacomechanical catheter-directed thrombolysis (PCDT) trial (NCT00790335) to assess the effects of PCDT on VEINES quality-of-life (VEINES-QoL) and Villalta scores for specific symptom-onset-to-randomization (SOR) timeframes. Results: Mice that developed RBF by day 4, but not later, exhibited reduced day 8 thrombus burden parameters and reduced day 8 vein wall fibrosis and inflammation, compared to controls. In mice without RBF, rtPA administered at day 4, but not later, reduced day 8 thrombus burden and vein wall fibrosis. Notably, in mice already exhibiting RBF by day 4, rtPA administration did not further reduce thrombus burden or vein wall fibrosis. In the ATTRACT trial, patients receiving PCDT in an intermediate SOR timeframe of 4-8 days demonstrated maximal benefits in VEINES-QoL and Villalta scores (between group difference=8.41 and 1.68 respectively, p<0.001 vs. patients not receiving PCDT). PCDT did not improve PTS scores for patients having an SOR time of <4 days or >8 days. Conclusions: Taken together, these data illustrate that within a restricted therapeutic window, RBF improves DVT resolution, and PCDT may improve clinical outcomes. Further studies are warranted to examine the value of time-restricted RBF strategies to reduce PTS in DVT patients.


2020 ◽  
Author(s):  
Siyu Bai ◽  
Hong Li ◽  
Li Li

Abstract Hitherto, research on the fluid-structure coupling of coronary stents has mostly considered the state after stent expansion following implantation. However, the factors and how they affect stent expansion are as yet, unclear. To further investigate stent expansion, this paper proposes a model combining balloon, stent, and blood using Solidworks. Thereafter, a co-simulation using ANSYS Workbench is implemented using the methods of finite element and finite volume, to analyze bidirectional fluid-structure coupling during the expansion of a balloon-expandable stent, for periodically varying blood loads. By comparing the blood flow rate in the vessel, pressure on the endovascular wall, and the pressure and stress on the stent system at different points in time, it can be seen that the higher the blood flow rate, the greater the pressure on the endovascular wall and stent system. Furthermore, the larger the volume of the implant, the greater the maximum blood flow rate and maximum pressure on the endovascular wall, and the more drastic the change along the axis. In summary, the results of the present study indicate that the stent expansion process has a significant effect on the blood flow rate and pressure on the vascular wall; however, the impact of blood load on stent stress can be ignored.


2014 ◽  
Vol 14 (05) ◽  
pp. 1450077
Author(s):  
YU CHEN ◽  
YAN XIONG ◽  
WENTAO JIANG ◽  
JIAN CHEN ◽  
MENG GUO ◽  
...  

The paper investigated the effects of the link numbers and geometries of drug-eluting stents (DESs) on the hemodynamics and the distribution of drug concentration, and the final results could be used as a guide for the optimization of DES design. Four 3D virtual stents with different numbers and geometries of links were modeled and numerically studied with respect to the distribution of wall shear stress (WSS) and drug concentration. Results have showed (1) The geometries of links have big impact on the distribution of WSS regions and the uniform drug concentration distribution on the vascular wall, but little effect on the mean drug concentration on the vascular wall; the S-shaped link stents had less low-WSS regions and the reason is that the flow direction was considered in the design of this type of stents. (2) The drug concentration distribution on the vascular wall had remarkable difference from that in blood. (3) The 6S link stent had the least low-WSS regions and with high and uniformly distributed drug concentration, so this type of stent was concluded to be the best design in four stents. Overall, it is not reliable to use the drug concentration in blood to deduce the drug concentration on the vascular wall. In DES design, the configuration of links should be, as much as possible, in line with the blood flow direction, so it can decrease the low-WSS regions. Meanwhile, in order to get more uniformly distributed drug on the vascular wall, the distribution of drug on the stent surface should be taken into account. Additionally, because of the increment of contact area between the stents and vascular wall, the drug concentration on the vascular wall increased with the number of links.


Author(s):  
Н.Н. Петрищев ◽  
Д.Ю. Семенов ◽  
А.Ю. Цибин ◽  
Г.Ю. Юкина ◽  
А.Е. Беркович ◽  
...  

The purpose. In the study we investigated the impact of the partial blood flow shutdown on structural changes in the rabbit vena cava posterior wall after exposure to high-intensity focused ultrasound (HIFU). Methods. Ultrasound Exposure: frequency of 1.65 MHz, the ultrasound intensity in the focus of 13.6 kW/cm, the area of the focal spot 1 mm, continuous ultrasound, exposure for 3 seconds. Results. Immediately after HIFU exposure all layers of the vein wall showed characteristic signs of thermal damage. A week after exposure structural changes in the intima, media and adventitia was minimal in the part of vessel with preserved blood flow, and after 4 weeks the changes were not revealed. A week after HIFU exposure partial endothelium destruction, destruction of myocytes, disorganization and consolidation of collagen fibers of the adventitia were observed in an isolated segment of the vessel, and in 4 weeks endothelium restored and signs of damage in media and adventitia persisted, but were less obvious than in a week after exposure. Conclusion. The shutdown of blood flow after exposure to HIFU promotes persistent changes in the vein wall. Vein compression appears to be necessary for the obliteration of the vessel, when using HIFU-technology.


2021 ◽  
Vol 11 (9) ◽  
pp. 4136
Author(s):  
Rosario Pecora

Oleo-pneumatic landing gear is a complex mechanical system conceived to efficiently absorb and dissipate an aircraft’s kinetic energy at touchdown, thus reducing the impact load and acceleration transmitted to the airframe. Due to its significant influence on ground loads, this system is generally designed in parallel with the main structural components of the aircraft, such as the fuselage and wings. Robust numerical models for simulating landing gear impact dynamics are essential from the preliminary design stage in order to properly assess aircraft configuration and structural arrangements. Finite element (FE) analysis is a viable solution for supporting the design. However, regarding the oleo-pneumatic struts, FE-based simulation may become unpractical, since detailed models are required to obtain reliable results. Moreover, FE models could not be very versatile for accommodating the many design updates that usually occur at the beginning of the landing gear project or during the layout optimization process. In this work, a numerical method for simulating oleo-pneumatic landing gear drop dynamics is presented. To effectively support both the preliminary and advanced design of landing gear units, the proposed simulation approach rationally balances the level of sophistication of the adopted model with the need for accurate results. Although based on a formulation assuming only four state variables for the description of landing gear dynamics, the approach successfully accounts for all the relevant forces that arise during the drop and their influence on landing gear motion. A set of intercommunicating routines was implemented in MATLAB® environment to integrate the dynamic impact equations, starting from user-defined initial conditions and general parameters related to the geometric and structural configuration of the landing gear. The tool was then used to simulate a drop test of a reference landing gear, and the obtained results were successfully validated against available experimental data.


Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 367
Author(s):  
Konstantinos Giannokostas ◽  
Yannis Dimakopoulos ◽  
Andreas Anayiotos ◽  
John Tsamopoulos

The present work focuses on the in-silico investigation of the steady-state blood flow in straight microtubes, incorporating advanced constitutive modeling for human blood and blood plasma. The blood constitutive model accounts for the interplay between thixotropy and elasto-visco-plasticity via a scalar variable that describes the level of the local blood structure at any instance. The constitutive model is enhanced by the non-Newtonian modeling of the plasma phase, which features bulk viscoelasticity. Incorporating microcirculation phenomena such as the cell-free layer (CFL) formation or the Fåhraeus and the Fåhraeus-Lindqvist effects is an indispensable part of the blood flow investigation. The coupling between them and the momentum balance is achieved through correlations based on experimental observations. Notably, we propose a new simplified form for the dependence of the apparent viscosity on the hematocrit that predicts the CFL thickness correctly. Our investigation focuses on the impact of the microtube diameter and the pressure-gradient on velocity profiles, normal and shear viscoelastic stresses, and thixotropic properties. We demonstrate the microstructural configuration of blood in steady-state conditions, revealing that blood is highly aggregated in narrow tubes, promoting a flat velocity profile. Additionally, the proper accounting of the CFL thickness shows that for narrow microtubes, the reduction of discharged hematocrit is significant, which in some cases is up to 70%. At high pressure-gradients, the plasmatic proteins in both regions are extended in the flow direction, developing large axial normal stresses, which are more significant in the core region. We also provide normal stress predictions at both the blood/plasma interface (INS) and the tube wall (WNS), which are difficult to measure experimentally. Both decrease with the tube radius; however, they exhibit significant differences in magnitude and type of variation. INS varies linearly from 4.5 to 2 Pa, while WNS exhibits an exponential decrease taking values from 50 mPa to zero.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1207.2-1207
Author(s):  
A. García Fernández ◽  
A. Briones-Figueroa ◽  
L. Calvo Sanz ◽  
Á. Andreu-Suárez ◽  
J. Bachiller-Corral ◽  
...  

Background:Biological therapy (BT) has changed the treatment and perspectives of JIA patients but little is known about when is the best moment to start BT and the impact of this prompt iniciation.Objectives:To analyze the response to BT of Juvenile Idiophatic Arthritis (JIA) patients according to the time when the BT was started.Methods:A retrospective, descriptive study was conducted on JIA patients followed up in a referal hospital that started BT up to 24 months after diagnosis from 2000 to 2018. Disease activity was measured, at 2 years after diagnosis, according to Wallace criteria for remission (absence of: active arthritis, active uveitis, fever, rash or any other manifestation attributable to JIA, normal CRP and ESR, PGA indicating no active disease) for at least 6 months.Results:55 JIA patients that started BT up to 24 months from diagnosis were analyzed. 69,1% were girls with a median age at diagnosis of 8 years old IQR(3-13), median age at the start of BT of 9 years old IQR(3-13). Regarding JIA categories: 25,5% were Oligoarticular Persistent (OligP), 18,2% Systemic JIA (sJIA), 16,4% Entesitis related Arthritis (ERA), 12,7% Psoriatic Arthritis (APso) and Polyarticular RF- (PolyRF-), 5,5% Oligoarticular Extended (OligE) and Polyarticular RF+ (PolyRF+), 3,6% Undifferentiated (Und). 20% of patients had uveitis during followup. Conventional DMARD (cDMARD) was indicated in 83,6% of patients (95,7% Methotrexate) at diagnosis [median 0 months IQR(0-2,3)]. At the end of followup (2 years) only 30,9% of patients continued with cDMARDs. The main causes of discontinuation were: adverse events (46,7%), remission (36,7%). TNF inhibitors were precribed in 81,8% of patients and 18,2% of patients recieved two BT during the first 2 years from diagnosis. 54,5% of BT were indicated during the first 6 months from diagnosis, 27,3% from 7 to 12 months, 12,7% from 13 to 18 months, 5,5% from 19 to 24 months.After 2 years from diagnosis, 78,2% of patients were on remission and 21,8% active. Among patients with active disease: 75% had arthritis, 16,7% had uveitis and 8,3% had both. There were no differences regarding disease activity among patients with uveitis and neither taking cDMARDs. Regarding JIA categories: 66,7% of OligE, 57,1% of PolyRF- and 57,1% of APso patients were active at 2 years from diagnosis when compared to the other categories (p=0.004).Patients on remission at 24 months from diagnosis started sooner the BT than active patients [CI 95% (0,46-8,29) p=0,029]. The time when the BT was started was correlated to the activity at 2 years (K= 0,294 p=0,029). When the BT was prescribed after 7,5months from diagnosis it was correlated, in a COR curve, with a higher probability of active disease at 2 years (S= 0,67 E= 0,63). There was a correlation, among patients on remission at 2 years, between prompt start of BT and less time to reach remission (K= -0,345 p=0,024). Patients with active disease at 2 years, regardless of moment of BT iniciation, required more BT during follow-up (p=0,002).Conclusion:Prompt iniciation of BT was correlated with a better outcome. JIA patients that started BT early after diagnosis had a higher probability of remission after 2 years. Starting BT after 7,5 months was correlated with a higher probability of active disease at 2 years. Active disease at 24 months was correlated with persistent active disease during follow-up.Disclosure of Interests:None declared


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