• Bulletin of the Korean Chemical Society
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• v.34 no.6
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• pp.1663-1667
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• 2013

Neointimal hyperplasia causes vascular access dysfunction in hemodialysis patients with synthetic arteriovenous (AV) grafts. Several studies have reported that paclitaxel- or sirolimus-eluting AV grafts inhibit neointimal hyperplasia and display lower rates of stenosis compared with control grafts. However, there have been few comparative studies of the efficacy of paclitaxel- and sirolimus-eluting grafts. We compared the neointimal hyperplasia of paclitaxel- and sirolimus-eluting grafts. AV grafts were implanted laterally between the common carotid artery and the external jugular vein in 12 female Landrace pigs. The animals were sacrificed six weeks after surgery. The neointimal hyperplasia at the anastomosis sites of the grafts was quantified using the ratio of the intragraft hyperplasia to the graft area (H/G ratio) at the graft-vessel interface. The area of intimal hyperplasia at the venous (paclitaxel 1.06 [0.72-1.56] vs sirolimus 2.40 [1.72-3.0] $mm^2$, P = 0.04) and arterial anastomosis sites (paclitaxel 0.93 [0.57-1.48] vs sirolimus 2.40 [1.72-3.0] $mm^2$, P = 0.04) was significantly different between the two groups. However, the H/G ratios for the venous anastomosis site (paclitaxel 0.25 (0.17-0.38) vs sirolimus 0.38 (0.2-0.66), P = 0.4) and the arterial anastomosis site (paclitaxel 0.19 (0.08-0.39) vs sirolimus 0.41 (0.34-0.50), P = 0.1) did not differ significantly between the groups. In conclusion, there was no significant difference in the inhibition of neointimal hyperplasia by sirolimus- and paclitaxel-eluting AV grafts.

• Natural Product Sciences
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• v.26 no.1
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• pp.71-78
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• 2020

The plant Dendropanax morbifera Léveille is effective folk medicines for the treatment of several conditions, such as infectious diseases, skin diseases, and other illnesses. Although the inhibitory effects of D. morbifera on the proliferation and migration of vascular smooth muscle cells (VSMCs) have been shown in our previous study, its effects in vivo remain to be elucidated. In this study, we aimed to investigate the protective effects of the extracts from D. morbifera (EDM) on neointimal hyperplasia of rat carotid artery and explore the underlying mechanisms. We observed that the ratio of intima to media thickness (I/M) was significantly decreased in the EDM-treated groups by ~80% compared to that of the control. The expression of Ki-67 and proliferating cell nuclear antigen was decreased by ~70% in the EDM-treated groups compared to that of the control. In addition, matrix metalloproteinase (MMP)2 and MMP9 significantly reduced in the neointimal layer of the EDM-treated groups. Moreover, the decreased levels of contractile phenotypic markers of VSMCs, such as α-smooth muscle actin, myocardin, and smooth muscle-myosin heavy chain, were successfully restored by EDM treatment. Furthermore, the levels of synthetic phenotypic markers, cellular retinal binding protein 1 and connexin 43 were also restored to normal levels. These results suggest that EDM inhibits vascular neointimal hyperplasia induced by balloon injury in rats via phenotypic modulation of VSMCs. Therefore, EDM may be a potential drug candidate for the prevention of restenosis.

• Bulletin of the Korean Chemical Society
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• v.31 no.2
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• pp.281-285
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• 2010

Hemodialysis vascular access dysfunction (HVAD) due to the aggressive development of venous neointimal hyperplasia remains a major complication for patients with synthetic arteriovenous grafts. Paclitaxel-coated expanded polytetrafluoroethylene (ePTFE) grafts effectively prevent neointimal hyperplasia and stenosis. However, perigraft inflammation or edema can be another complication of ePTFE grafts, preventing early cannulation. Three different types of ePTFE grafts, including grafts without paclitaxel coating (control group, n = 12), grafts with paclitaxel coating at a dose density of $0.61ug/mm^2$ (low concentration group, n = 12), and grafts with paclitaxel coating at a dose density of $1.15ug/mm^2$ (high concentration group, n = 12) were placed in the backs of 12 rabbits, simultaneously. Six rabbits were euthanized after one week and the remaining six were euthanized two weeks after implantation. Perigraft inflammation, graft wall inflammation, stromal cell proliferation, blood vessel formation, tissue necrosis and edema were analyzed for the grafts in each animal. Inflammation surrounding the paclitaxel-coated grafts was significantly reduced compared to the control group. Stromal cell layers were detected at the interface between the graft and the surrounding tissue in the control group, infiltrated into the graft interstices, and differentiated into myofibroblasts for graft healing. Paclitaxel-coated grafts inhibited stromal cell proliferation and infiltration into the graft wall. Tissue necrosis and edema were not detected in either of the paclitaxel-coated graft groups.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.2
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• pp.113-119
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• 2006

Coronary artery disease is a loading cause of morbidity and mortality across the world. Percutaneous coronary intervention has become the major technique of revascularization. However, restenosis remains a major limitation of this procedure. Recently the need for repeat intervention due to restenosis, the most vexing long-term failure of percutaneous coronary intervention, has been significantly reduced owing to the introduction of two major advances, intracoronary brachytherapy and the drug-eluting stents. Intracoronary brachytherapy has been employed in recent years to prevent restenosis lesions with effective results, principally in in-stent restenosis. Restenosis is generally considered as au excessive form of normal wound healing divided up in precesses: elastic recoil, neointimal hyperplasia, and negative vascular remodeling. Restenosis has previously been regarded as a proliferative process in which neointimal thickening, mediated by a cascade of inflammatory mediators and other factors, is the key factor. Ionizing radiation has been shown to decrease the proliferative response to injury in animal models of restenosis. Subsequently, several randomized, double blind trials have demonstrated that intracoronary brachytherapy can reduce the rates of both angiographic restenosis and clinical event rates in patients undergoing percutaneous coronary intervention for in stent restenosis. Some problems, such as late thrombosis and edge restenosis, have been identified as limiting factors of this technique. Brachytherapy is a promising method of preventing and treating coronary artery restenosis.

• 대한핵의학회:학술대회논문집
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• 1999.05a
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• pp.205-208
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• 1999

Percutaneous Transluminal Coronary Angioplasty (PTCA) remains limited by restenosis that occurs in 30 to 50% of patients with coronary artery disease. During the last decade, numerous agents have been used to prevent restenosis. Despite positive results in animal models, no pharmacological therapy has been found to significantly decrease the risk of restenosis in humans. These discrepancies between animal models and clinical situation were probably related to an incomplete understanding of the mechanism of restenosis. Neointimal thickening occurs in response to experimental arterial injury with a balloon catheter. Neointimal formation involves different steps: smooth muscle cell activation, proliferation and migration, and the production of extracellular matrix. The factors that control neointimal hyperplasia include growth factors, humoral factors and mechanical factors. Arterial remodeling also plays a major role in the restenosis process. Studies performed in animal and human subjects have established the potentials for "constrictive remodeling" to reduce the post-angioplasty vessel area, thereby indirectly narrowing the vessel lumen and thus contributing to restenosis. The reduction of restenosis rate in patients with intracoronary stent implantation has been attributed to the preventive effect of stent itself for this negative remodeling. In addition to these mochanisms for restenosis, intraluminal or intra-plaque thrombus formation, reendothelialization and apoptosis theories have been introduced and confirmed at least in part.

• Journal of Biomedical Engineering Research
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• v.13 no.4
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• pp.313-322
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• 1992

A finite analytic(FA) numerical study was performed to determin'e flow dynamics in the vicinity of an end-to-end anastomosis. Experimental data of instantaneous lumen cross-section were used to simulate steady flow through an end-to-end anastomosis In order to solve the governing axisymmetric Wavier-Stokes equations. Wall shear stresses increased proximal to the anastomosis In flow from the Penrose tubing to the PTFE graft. In flow the PTFE graft to the Penrose tubing, low wall shear stresses were observed distal to the anastomosis. The present study suggests a correlation betweerl regions of low wall shear stress and the do velopment of pnastomotic neointimal fibrous hyperplasia(ANFH ) in end-to-end anastomoses.

• Journal of Biomedical Engineering Research
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• v.6 no.2
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• pp.9-12
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• 1985

The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses.

• Proceedings of the KSME Conference
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• 2003.04a
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• pp.1919-1922
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• 2003

Bypass anastomosis are frequently adopted for surgical treatments. After the bypass grafting, the bypass artery is often occluded due to restenosis and/or anastomotic neointimal fibrous hyperplasia phenomena. Optimal coronary bypass anastomosis should be investigated to improve the patency for the arterial bypass techniques. The objective of this study is to investigate the influence of bypass with sequential bypass effects in the stenosed coronary artery. Numerical analyses are focused on the understanding of the flow patterns for different sequential anastomosis techniques. Blood flow field is treated as two-dimensional incompressible laminar flow. The finite volume method is adopted for discretization of the governing equations. The Carreau model is employed as the constitutive equation for blood. To find the optimal sequential bypass anastomotic configurations, the mass flow rates at the outlet of different models are compared quantitatively.

• Journal of Biomedical Engineering Research
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• v.13 no.3
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• pp.253-262
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• 1992

The wall shear stress in the vicinity of end-to end anastomoses under steady flow condi- tions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experi- mental measurements were in good agreement lith numerical results except In flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compli- ance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia (ANFH) in end-to-end anastomoses.

• Proceedings of the KOSOMBE Conference
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• v.1996 no.11
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• pp.254-257
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• 1996

An aorto-coronary bypass graft is frequently adopted for the interventional therapy of the diseased atherosclerotic coronary artery grafting. The bypass artery is often occluded due to restenosis and/or anastomotic neointimal fibrous hyperplasia after bypass graft. The optimal aorto-coronary bypass procedure must be studied in order to improve patency rate for the arterial bypass techniques. The objective of this study is to investigate the influences of geometric dimensions of bypass on the hemodynamics around the anastomosis in the stenosed coronary artery with aorto-coronary bypass.