• Bulletin of the Korean Chemical Society
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• 제34권6호
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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.

• 대한의용생체공학회:의공학회지
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• 제13권4호
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• pp.339-352
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• 1992

A numerical simulation of the steady and pulsatile flow across the end-to-side anastomosis was performed In order to understand the role of flow dynamics in the preferential bevel opment of distal anastomotic intimal hyperplasla. The finite element technique was employed to solve two-dimensional unsteady pulsatile flow in that region. The results of the steady flow revealed that low shear stresses occur at the proximally occluded host artery and at the recirculation region in the Inner wall just distal to the toe region of the anastomosis. The nor- mal;zed wall shear rate was increased, as was the recirculation zone size in the host artery of the by-pass graft anastomosis, with increased anastomotic junction angle. In order to min imize the size of the low wall shear region which might result in the intimal hyperplasia in the by-pass graft anastomosis, a smaller anastomotic junction angle is recommended. The pulsatile flow simulation revealed flow that regions of low and ascillating mali shear do exist near the anastomosis as In the steady simulation. The shift of stagnation point depends on the pulsation of the flow. As the flow was accelerated at systole, the stagnation point moved downstream, disappered at early diastole and reappeared during late diastole. Low shear stress was also found along both walls of the occluded proximal artery. However, the diastolic flow behavior is quite different from the steady results. The vortex near the occluded artery moved downstream and inwardly during late systole, and disappeared during diastole. Recirculations proximal to the toe and heel regions were significant during diastole. Shear stress oscillation was found along the opposite wall. The results of the present study revealed that tow shear occurs at the proximally occluded host artery aud the recirculation region in the inner wall Just dlstal to the toe region of the anastomosis. The present study suggested that the regions of fluctuated wall shear stress wit flow separation is correlated with the preferential developing regions of anastomosis neointial fibrous hyperplasia.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제16권3호
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• pp.397-418
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• 1994

Microvascular surgery has been widely used in the clinical field of replantation and reconstructive surgery. Since the last 20 years, microsurgical techniques and instruments have been rapidly developed and the success rate is remarkably increased. But thrombotic occlusion of vessels remains the major reason for clinical failure. The change of vessel wall is the most important factor in thrombus formation. If we can reduce the traumatic changes in the vessel walls during surgery, the success rate can be markedly increased. For this study, femoral arteries and veins of 36 Sprague-Dawley rats with average weights of 300gm were used. The author observed the histological changes and healing process in the anastomostic site after 1 hour, 24 hours, 1, 2, 3 and 4 weeks under light microscopy and scanning electron microscopy. The results were as follows : 1. The patency rate was 100% in femoral arteries and 85% in femoral vein. 2. At the early stages after microvascular anastomosis, the loss of endothelial cell in the vessel walls was observed in the wide area including anastomotic site. In scanning electron microscopic finding the anastomotic site was covered with much fibrin, many red blood cells and some platelets. 3. At 1st week, new endothelial cells were formed toward anastomotic site and at 3rd week, the anastomotic site was completely covered by new endothelial cells. At 4th week, the complete endothelialization over the threads was observed. 4. The media extended from the anastomotic site toward the end of the specimen. At later stages, the extent of media necrosis was markedly decreased. But the media necrosis of anastomotic site was not regenerated till 4th week. 5. Intimal hyperplasia appeared at 1st week and increased till 4th week. The layer consisted of endothelialization the most luminal layers and smooth muscle in the deeper layers. But in veins, the response was less pronounced than in arteries. 6. Foreign body granuloma remained during 4 weeks and aneurysm was observed at 3rd week in artery. In aneurismal wall, media necrosis, loss of elastic lamina and intimal hyperplasia were seen.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제22권1호
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• pp.22-32
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• 2000

Purpose : Histopathologic observation was performed in order to determine which type of suture material is superior in microvascular anastomoses. Materials & Methods : The interrupted end to end anastomosis of the transected carotid arteries of 105 Sprague-Dawley rats, weighing 180 to 200g, were performed using 9-0 polypropylene ($Prolene^{TM}$, Ethicon, U.K.), 9-0 polyglactin 910 monofilament($Vicryl^{TM}$, Ethicon, U.K.), and 9-0 polyamide($Ethilon^{TM}$, Ethicon, U.K.) under intramuscular Ketamine and Xylazine anesthesia(5mg/100g). In all cases, 10 to 12 sutures were placed to complete the anastomoses. The specimens were obtained at 1, 2, 3 days, and 1, 2, 4 and 6 weeks after the surgery and prepared with H&E and Van-Gieson stains and investigated the histologic changes in anastomotic sites under light microscope. The histologic changes we were concerned about were followings- thrombus formation, intimal edema, infiltration of inflammatory cells in media and adventitia, proliferation of endothelial cells and subintimal hyperplasia. Results : 1. All of the anastomosed arteries were patent when they were exposed for examination. 2. Thrombus formation and intimal edema were most severe in Vicryl group, followed by Ethilon, Prolene group in order. 3. The inflammatory cells infiltrated to the media and the adventitia most severely in Ethilon group, followed by Vicryl, Prolene group in order. 4. There was little difference in proliferation of endothelial cells in each group. 5. Subintimal hyperplasia was greater in Vicryl group than the others, but there was no significant difference between the Prolene and Ethilon groups. Conclusions : On the basis of these observations, we could conclude that Prolene may be the better suture material for microvascular anastomoses regarding the tissue responses than Ethilon and Vicryl.

• Natural Product Sciences
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• 제26권1호
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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.

• Journal of Mechanical Science and Technology
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• 제19권3호
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• pp.905-912
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• 2005

A computational investigation of blood flow in a coronary artery grafted by artificial bypass was performed to determine such geometric parameters as the curvature of radius, approach length, and angle of end-to-side anastomosis. Transient flow features in the host artery were computed using FVM and SIMPLE algorithms. We compared flow distributions and wall shear stresses in two simple models, planar and non-planar, and confirmed that the non-planar bypass model was more conducive to suppressing intimal hyperplasia. Our non-planar model with $60^{\circ}$ of anastomosis and a 1.0 diameter approach length and radius of curvature predicts a relatively small, spatially-extended high-OSI (>0.01) zone, as well as an increased average wall shear stress on this zone.

• 한국전산유체공학회지
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• 제18권3호
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• pp.14-19
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• 2013

Renal failure patients have to operate arteriovenous graft for hemodialysis. Blood flow characteristics influence the patency rate of arteriovenous graft. Numerical investigation is performed with the arteriovenous graft according to injection of blood. As a result, when the injection is not applied to venous graft, the low wall shear stress region appears at venous anastomosis. It may cause intimal hyperplasia at venous anastomosis.

• 대한의용생체공학회:의공학회지
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• 제20권5호
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• pp.593-599
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• 1999

수축절정기에 0.2mm, 0.4mm 두께의 소구경 인조혈관의 내경3.2mm의 동맥에 문합한 단단문합 주위의 유동과 구조해석을 동시에 수행하였다. 유동해석 결과 속도분포 및 벽단전률은 타 연구결과와 매우 유사하며 이론해와 매우 유사함을 보였다. 유동에 의해서 문합부 주위에 작용하는 응력은 문합부에 집중되며 이는 수십만 pa에 달했다. 또한 인조혈관과 동맥에 작용하는 원주방향의 응력을 이론해와 비교한 결과 서로 유사함을 보였으며 두께가 얇은 인조혈관을 사용하는 경우 문합부의 compliance mismatch 는 개선되나 반대로 응력은 더 많이 받음을 알 수 있었다. 본 연구를 통해서 유체에 의하여 혈관이 영향을 받는 심혈관계 현상을 연구하는데 있어서 이와 같은 유체-구조 상호작용을 고려하여 동시에 해결 하는 방법은 매우 유용할 것으로 생각된다.

• Molecules and Cells
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• 제43권8호
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• pp.749-762
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• 2020

The migration, dedifferentiation, and proliferation of vascular smooth muscle cells (VSMCs) are responsible for intimal hyperplasia, but the mechanism of this process has not been elucidated. WD repeat domain 1 (WDR1) promotes actin-depolymerizing factor (ADF)/cofilin-mediated depolymerization of actin filaments (F-actin). The role of WDR1 in neointima formation and progression is still unknown. A model of intimal thickening was constructed by ligating the left common carotid artery in Wdr1 deletion mice, and H&E staining showed that Wdr1 deficiency significantly inhibits neointima formation. We also report that STAT3 promotes the proliferation and migration of VSMCs by directly promoting WDR1 transcription. Mechanistically, we clarified that WDR1 promotes the proliferation and migration of VSMCs and neointima formation is regulated by the activation of the JAK2/STAT3/WDR1 axis.

• Journal of Chest Surgery
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• 제42권2호
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• pp.135-140
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• 2009

배경: 동종이형의 심장이식 후에 나타나는 만성 거부반응은 수술 후 약 6개월이 지나 나타나며, 이로 인해 이식된 심장의 관상동맥의 동맥 경화 소견과 심장의 손상을 일으키는 혈관병증이 나타나는 바, 대혈관인 대동맥에서도 이러한 소견을 보이는 지를 확인하고자 하였다. 대상 및 방법: $200{\sim}300gm$의 백서(Spraque-Dawley Rat)에서 이소성의 동종이형의 심장이식(heterotopic heart alto-transplantation)을 Ono-Lindsey method로 시행한 후 사이클로스포린(cyclosporin A 10mg/kg/day, 종근당 제공)을 투여하여 3개월 이상 생존한 군에서 동물을 희생시킨 후 자가 상행 대동맥과 이식된 심장의 대동맥에서 각각 조직 절편을 얻어 조직 검사를 시행하여 비교하였다. 자가 상행 대동맥의 조직 검사(N=9, native ascending aorta)와 동종 이형의 이식된 심장의 대동맥(N=13, alto-transplanted aorta)의 조직 검사를 동종이형의 심장이식 후의 만성 거부 반응의 특징적인 조직 검사 소견인 1) 내막 비후(intimal thickening), 2) 중층 비후(medial hyperplasia), 3) 중층 석회화(medial calcification), 4) 중층 염증(medial inflammation), 5) 연골 화생(chondroid metaplasia)에 대하여 한 명의 병리의에 의해 대조군과 이식군에서 각각 심한 정도를 통계처리(Mann-Whitney Test, SPSS version 12.0 Windows)하여 비교하였다. 결과: 중층 비후 외(p=0.36)에 내막 비후(p<0.0001), 중층 석회화(p=0.045), 중층 염증(p<0.0001), 연골 화생(p=0.045)에 있어 이식된 심장의 대동맥에서 의미 있는 변화를 보였다. 결론: 동종 이형의 심장 이식 후에 만성 거부 반응에 의한 혈관병증(cardiac allograft vasculopathy)은 관상 동맥을 침범하여 심근의 손상을 가져오며, 이와 같은 만성 거부 반응에 의한 혈관 병증의 변화는 대혈관인 이식된 대동맥에서도 상기의 결과와 같이 나타나 대동맥에서도 만성적인 거부 반응이 진행되고 있음을 확인할 수 있었다.