- Open Access
Numerical simulation on the effects of drug eluting stents at different Reynolds numbers on hemodynamic and drug concentration distribution
- Yu Chen†1,
- Yan Xiong†2,
- Wentao Jiang1Email author,
- Fei Yan1,
- Meng Guo3,
- Qingyuan Wang1 and
- Yubo Fan3
© Chen et al.; licensee BioMed Central Ltd. 2015
Published: 9 January 2015
The changes of hemodynamics and drug concentration distribution caused by the implantation of drug eluting stents (DESs) in curved vessels have significant effects on In-Stent Restenosis.
A 3D virtual stent with 90°curvature was modelled and the distribution of wall shear stress (WSS) and drug concentration in this model were numerically studied at Reynolds numbers of 200, 400, 600, 800.
The results showed that (1) the intensity of secondary flow at the 45° cross-section was stronger than that at the 90° cross-section; (2) As the Reynolds number increases, the WSS decreases. When the Reynolds number reaches 600, the low-WSS region only accounts for 3% of the total area. (3) The effects of Reynolds number on drug concentration in the vascular wall decreases in proportionally and then the blood velocity increased 4 times, the drug concentration in the vascular wall decreased by about 30%. (4) The size of the high drug concentration region is inversely proportional to the Reynolds number. As the blood velocity increases, the drug concentration in the DES decreases, especially at the outer bend.
It is beneficial for the patient to decrease vigorous activities and keep calm at the beginning of the stent implantation, because a substantial amount of the drug is released in the first two months of stent implantation, thus a calm status is conducive to drug release and absorption; Subsequently, appropriate exercise which increases the blood velocity is helpful in decreasing regions of low-WSS.
Atherosclerosis is a specific form of arteriosclerosis in which an artery wall thickens as a result of the accumulation of cholesterol and triglyceride . Drug eluting stents (DESs) in cardiovascular surgery significantly reduce the rate of restenosis caused by in-stent intimal hyperplasia  and have been considered and accepted as one of the most promising treatment methods for preventing restenosis .
The blood flow in humans and animals is always laminar, and only in abnormal conditions is there turbulent blood flow for a long time . Qu et al. found that with age the fluctuation ranges of normal value increased and the mean blood velocity decreased. Yin et al. found that the blood velocity in the basilar and carotid arteries in normal humans decreased with age, with the blood velocity in the range 0.2 m-0.8 m/s. Normally, the peak of diastolic velocities in a human coronary artery is 500 ± 170 mm/s, with a mean blood velocity of 370 ± 120 mm/s. With cardio intervention, the average peak velocity (APV) at the proximal and distal increases and the coronary flow reserve (CFR) improves . In addition, the blood velocity for humans when in motion increases up to 30% even higher . From the viewpoint of biomechanics, factors such as blood flow velocity, impact flow, pressure and wall shear stress (WSS) have important effects on atherosclerosis. Seo et al. discussed that how to reduce erratic flow at different Reynolds numbers for different curvature stents. Sukavaneshvar et al. analyzed the hemodynamics on the two restenosis positions at two different Reynolds numbers. Kolachalama et al. discussed the changes of drug concentration, the Area Under Curve(AUC) and the recirculation length at 2, 4, 6 and 8 times Reynolds number. Chen et al. analyzed the effects of drug-coating positions on the drug concentration in curved stents and found that the contribution of the contacting surface to the drug concentration in the vascular wall was underestimated in 2D numerical simulation. The implantation of stents into coronary arteries can influence the fluid dynamics in the regions adjacent to the arterial wall, and consequently cause damage to the regional arterial wall and a change of WSS. Especially when a drug eluting stent (DES) is implanted in a curved vessel, secondary flow arises due to the curvature. Secondary flows occur in the cross-stream direction caused by the base primary flow in the streamwise direction . Secondary flow structures may affect the wall shear stress in arteries, and is closely related to atherogenesis. So the relationships between stent design and placement, drug release, deposition concentration, distribution of low-WSS, and secondary flow are important issues in research on stents. Autumn et al. compared the change of secondary flow, with and without stents, through PIV experiments. Jung et al. thought that the accumulation of red blood cells on the inner curvature was caused by the secondary flow and higher residence times. Bioron et al. analysed the behaviour of unsteady flows in a bend with experimental and numerical simulation. Sun et al. discussed the flow characteristics in a 90° bent pipe at different Reynolds numbers, and put forward the view that the higher the Reynolds number, the larger the pressure on the pipe wall. Stoesser et al. compared the results of numerical simulation and experimental data for the flow and wall shear stress distributions in a meandering open channel. The emphasis of the aforementioned literature is on secondary flow in a curved channel or pipe, but research on the implantation of a stent in a curved vessel is sparse, therefore it is necessary to study the effects of secondary flow on the hemodynamics and drug distribution in curved vascular walls.
This paper applies the method of computational fluid dynamics (CFD) to investigate the effects on hemodynamics and drug concentration in a 3D 90° DES. At different Reynolds number the relationship between hemodynamics, drug concentration and in-stent restenosis was also studied. The results can provide a theoretical guidance for optimization of the design of DES.
GAMBIT 2.3 (ANSYS, Inc., USA) software was used to build the model. Unstructured meshes were applied to the model. Grids were refined at the stent and vascular surface to improve computational accuracy. The refinement on the meshes continued until the computational results reached grid-independence. A mesh number of about 3 million cells of the 90°curved stent was finally adopted in the following investigation.
where ρ and μ are the density and dynamic viscosity of blood, respectively, ρ = 1055 kg/m3, μ = 3.5 × 10-3kg/m·s; P is pressure, and u i is the velocity vector of blood.
V z , V r are the velocities in the axial and radial directions of the blood flow, respectively. r = 0.0015m.
The drug concentration was set to zero at the luminal inlet (Eq. 5), and an open boundary condition was applied at the distal boundary. The drug transport within the tissue was modelled as a simple diffusion process, with an impermeable boundary condition on the perivascular wall (shown in Eq. 6). The boundary condition of the continuity flux in drug transport is shown in Eq.7, which allows the entire drug in the blood at the tissue-blood interface to be transported into the arterial tissue. The drug release of the stents was simulated as a Dirichlet boundary condition (Eq. 9), with a drug concentration of unity at the strut surfaces.
The computations were conducted by using a commercial CFD package, FLUENT 6.3 (ANSYS Inc.), in which a finite volume method was used to discretize the governing equations. 3D single-precision format and a segregated solver were used. The SIMPLEC algorithm was applied to complete the velocity-pressure correction. The standard format was chosen for the pressure discretization and 2nd-order upwind for the momentum equations. The residual error convergence threshold was set as 0.0001.
In the case of Newtonian fluids, Dean Vortices appear as a pair of vortices in curved ducts or bends because of flow inertia. When fluid is directed around a curve under a pressure driven flow, the high velocity streams in the centre of the channel experience a greater centripetal force and so are deflected outward . The Dean number (Dn) is a dimensionless group in fluid mechanics, which occurs in the study of flow in curved pipes and channels .
Dn = Re × (r/R)1/2
Re --- Reynolds number
r --- The diameter of the pipe
R --- Bend radius
When the Dean number is greater than 36, the fluid appears unstable phenomenon. The Reynolds numbers are 200, 400, 600, 800. In this paper, thus the Dean numbers are calculated as 77.5, 155, 232, and 310, respectively.
Velocity in cross-section
Obviously, the curved stent model at smaller Reynolds numbers has more low-WSS regions, which implies that it might be the most susceptible to in-stent restenosis. There are more low-WSS regions on the inner bend that on the outer bend. When the Reynolds number is larger than 600, the low-WSS ratio is less than 3%, which helps improve the in-stent restenosis.
Atherosclerosis in carotid arteries and coronary arteries, abdominal aorta, renal artery and aortic arch, after DES implanted in blood vessels, causes the velocity of the blood flow to be different in different parts of the human body. There is a lack of quantitative researches on the effects of the WSS and drug concentration in the blood and vascular wall at different Reynolds number.
Some diseases may make the blood flow velocity faster or slower, dynamic changes in the blood viscosity would lead to changes in the blood velocity. The elderly are susceptible to hyper viscosity, and there are many factors that affect the blood viscosity: blood cell factors, such as blood cells number, size, shape, RBC deformability, platelet function, etc; plasma reasons, such as plasma proteins (especially fibrinogen, immune globulin), blood glucose, blood lipid, fibrin lytic activity, etc; vascular factors, such as length, diameter and lining smoothness, etc; other factors, such as emotions, life style, smoking, drinking, etc. Common features of these diseases, such as atherosclerosis, moyamoya disease, vasculitis, partial recanalization, inflammation, and tumor thrombus, are caused by vascular stenosis. Radioactive damage caused by artery stenosis, dissecting aneurysm, and vasospasm is one of the reasons causing artery stenosis. For healthy human beings there are similar situations, the velocity of the blood flow changes according to the different statuses of the body: when undertaking sports, the velocity of the blood flow will be faster; when at rest and the velocity of the blood flow will be relatively slower.
We can see clearly the effects of Reynolds number on the WSS and drug concentration. When the Reynolds number increases, the low-WSS region gradually decreases, for a Reynolds number of 600, the percentage of the low-WSS region is less than 3%, and the Reynolds number of 800, the percentage decreases to 1%, with the effect of low-WSS almost negligible. Therefore, as the Reynolds number increases, the low-WSS region decreases.
Increasing blood flow velocity leads to a decrease of the drug concentration in the vascular walls, for example, increasing Reynolds number to 400 from 200, the drug concentration drops 8% approximately, but increase to 800 from 200 that is four times of original value 200, causes the drug concentration to decrease by 30% approximately. The effects of decreasing drug concentrations on the outer bend are greater than that on the inner bend.
The intensity of secondary flow on the 45° cross-section was stronger than that on the 90° cross-section, meaning that the enhancement of flow in the circumferential direction leads to a decrease of the low-WSS region;
With increasing Reynolds number, the region of low-WSS decreased. When the Reynolds number is larger than 600, the region of low-WSS is smaller than 3%.
The effects of Reynolds number on drug concentration in the vascular wall decreased proportionally and as blood velocity increased 4 times, the drug concentration in the vascular wall decreased by 30%.
As the blood velocity increased, the drug concentration in the DES decreased, especially on the outer bend.
When the DES is implanted in the blood vessel, it is beneficial for the patient to decrease vigorous activities and keep calm at the beginning of stent implantation, because a substantial amount of drug is released in the first two months of stent implantation, and calmness is conducive to drug release and absorption. Later, appropriate exercise can achieve higher blood velocity which is helping in decreasing regions of low-WSS.
This work is supported by Grants-in-Aid from the National Natural Science Research Foundation of China (No. 61190123, 51205262, 10872138) and Applied Basic Research Programs of science & technology department of Sichuan Province (No. 2014JY0148).
Publication of this article was paid with funding from Grants-in-Aid from the National Natural Science Research Foundation of China (No. 61190123, 51205262, 10872138) and Applied Basic Research Programs of science & technology department of Sichuan Province (No. 2014JY0148).
This article has been published as part of BioMedical Engineering OnLine Volume 14 Supplement 1, 2015: Cardiovascular Disease and Vulnerable Plaque Biomechanics. The full contents of the supplement are available online at http://www.biomedical-engineering-online.com/supplements/14/S1
- Kumar V, Cotran RS, Robbins SL: Basic Pathology. WB Saunders; 1992.Google Scholar
- Chen J, Ni Z, Gu X: Survey of coronary stents development for restenosis prevention. Chinese journal of medical instrumentation 2009, 33(6):429–434.Google Scholar
- Acharya Ghanashyam, Park Kinam: Mechanisms of controlled drug release from drug-eluting stents. Advanced Drug Delivery Reviews 2006, 58: 387–401. 10.1016/j.addr.2006.01.016View ArticleGoogle Scholar
- Wang XQ: The application of Reynolds number in biology. Journal of Qinghai University 2003, 21(5):67–69.Google Scholar
- Qu SB: Transcranial doppler ultrasound instrument detection of carotid artery blood flow velocity normal reference range. Journal of harbin medical university 1994, 28(3):211–213.Google Scholar
- Yin AY: Transcranial doppler ultrasound measurement in normal human brain artery and carotid artery blood flow velocity. Chinese Journal of Ultrasound in Medicine 1996, 12(12):60–64.Google Scholar
- Wei M: Doppler blood flow velocity measurement evaluation coronary angioplasty and curative effect of stenting PCI. Chinese Journal of Cardiology 1999, 27(5):337–339.Google Scholar
- Du W: The effects of exercise on human artery blood flow velocity. Journal of Beijing Sport University 1996, 8(2):14–17.Google Scholar
- Taewon Seo, Schachter LevantoG: Computational Study of Fluid Mechanical Disturbance Induced by Endovascular Stents. Annals of Biomedical Engineering 2005, 33(4):444–456. 10.1007/s10439-005-2499-yView ArticleGoogle Scholar
- Sukavaneshvar Sivaprasad, Gesse M: Rosa Enhancement of Stent-Induced Thromboembolism by Residual Stenoses: Contribution of Hemodynamics. Annals of Biomedical Engineering 2000, 28: 182–193.View ArticleGoogle Scholar
- Kolachalama VijayaB, Tzafriri AbrahamR: Luminal flow patterns dictate arterial drug deposition in stent-based delivery. Journal of Controlled Release 2009, 13: 24–30.View ArticleGoogle Scholar
- Chen Yu, Yan Fei, Jiang Wen-tao, Wang Qing-yuan, Fan Yu-bo: Numerical Study on the Effects of the Drug-coating Positions of Drug-eluting Stents on Drug Concentration, Journal of Medical and Biological Engineering. 2013.Google Scholar
- Zhan H, Zhang X, Dai C: Influence of Secondary Flow in Water-only Cyclone on its Separation Mechanism. Mining and Metallurgical Engineering 2002, 2: 017.Google Scholar
- Glenn AL, Bulusu KV, Shu F, et al.: Secondary flow structures under stent-induced perturbations for cardiovascular flow in a curved artery model. International Journal of Heat and Fluid Flow 2012, 35: 76–83.View ArticleGoogle Scholar
- Glenn AL, Bulusu KV, Shu F: Secondary flow structures under stent-induced perturbations for cardiovascular flow in a curved artery model. International Journal of Heat and Fluid Flow 2012, 35: 76–83.View ArticleGoogle Scholar
- Jung J, Lyczkowski RW, Panchal CB: Multiphase hemodynamic simulation of pulsatile flow in a coronary artery. Journal of biomechanics 2006, 39(11):2064–2073. 10.1016/j.jbiomech.2005.06.023View ArticleGoogle Scholar
- Boiron O, Deplano VER, Pelissier R: Experimental and numerical studies on the starting effect on the secondary flow in a bend. Journal of Fluid Mechanics 2007, 574: 109–130.MATHView ArticleGoogle Scholar
- Sun Y, Hu S, Zhao J: Numerical study on flow characteristics of 90 bend pipe under different reynolds number. Journal of University of Shanghai for Science and Technology 2010, 6: 005.Google Scholar
- Stoesser T, Ruether N, Olsen NRB: Calculation of primary and secondary flow and boundary shear stresses in a meandering channel. Advances in Water Resources 2010, 33(2):158–170. 10.1016/j.advwatres.2009.11.001View ArticleGoogle Scholar
- Chen Y, Jiang W, Chen X, Zheng T, Wang Q, Fan Y: Numerical simulation on the effects of drug-eluting stents with different links on hemodynamics and drug concentration distribution. Journal of Mechanics in Medicine and Biology 2013., 13(04):Google Scholar
- Balakrishnan B, Dooley JF, Kopia G: Intravascular drug release kinetics dictate arterial drug deposition, retention, and distribution. Journal of Controlled Release 2007, 123(2):100–108. 10.1016/j.jconrel.2007.06.025View ArticleGoogle Scholar
- Howell PB Jr, Mott DR, Golden JP: Design and evaluation of a Dean vortex-based micromixer. Lab on a Chip 2004, 4(6):663–669. 10.1039/b407170kView ArticleGoogle Scholar
- Ali S: Pressure drop correlations for flow through regular helical coil tubes. Fluid Dynamics Research 2001, 28(4):295–310. 10.1016/S0169-5983(00)00034-4View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.