Objective To study the mechanism of restenosis of the vein graft and the effect of the grafting injury to the vein graft. Methods One side of the 36 healthy rabbits was randomly chosen as the V-A group, and on the side a 1.5cmlong femoral vein was obtained, and an 0.5-cm-long segment of the obtained femoral vein was separated as the control group. The remaining 1-cm-long femoral vein was inverted and was autogenously implanted into the femoral artery on the same side of the rabbit. The other side of the rabbits was chosen as the V-V group, and on this side a 1-cm-long femoral vein was obtained ex vivo and then was sutured in situ. The vein grafts on both sides were harvested 4 weeks after operation. The specimens from the harvested vein grafts were stained with HE and theelastic fiber Victoria blue for an observation on the histological changes in the walls of the vein grafts, and the specimens were also stained by the immunohistochemistry of the proliferating cell nuclear antigen (PCNA) for an observation on the wall cell proliferation of the vein grafts. The changes in the ultrastructure of the proliferated wall cells of the vein grafts were observed under electron microscope. The two sides of the rabbits were compared. Results The smooth muscle cells of the media developed hyperplasia, but theintima and the media remained unchanged in their thickness (3.50±0.41 μm, 12.23±1.59 μm) in the V-V group, with no difference when compared with the control group (3.40±0.37 μm, 12.14±1.62 μm); however, when compared with the V-A group (25.60±3.21 μm, 21.30±2.47 μm),there was a significant difference in the thickness (Plt;0.01). There were no cells positive for PCNA by the immunohistochemistry examination in the control group. The cells positive for PCNA were found in the intima and the media in both the V-V group and the V-A group; however, the percentageof the cells positive for PCNA in the intima and the media was significantly greater in the V-A group than in the V-V group (16.4%±1.9% and 36.5%±3.7% vs 5.9%±1.3% and 23.4%±3.4%, Plt;0.01). In the V-V group, the endothelial cell could be observed under transmis-sion electron microscope, which was flat and had a processlike villus at its free end, and the endothelial cells were closely arranged andhad hyperplasia of the smooth muscle cells in the media. But in the V-A group,the endothelial cells had an obvious hyperplasia with an irregular shape and a widened space between the cells, and in the intima a great amount of the smooth muscle cells could be observed, which had a broken basement membrane. The smooth muscle cells also had an obvious hyperplasia in the media. The shape and alignment of the endothelial cells in the control group were similar to those in the V-V group, but the hyperplasia of the smooth muscle cells was not observed in the media. Conclusion The grafting injury can cause hyperplasia ofthe vascular wall cells, and if the hemodynamics is changed simultaneously, more serious hyperplasia and cell migration can be observed from the media to the intima, resultingin restenosis of the blood vessels. So, if we can reduce the grafting injury and improve the microcirculation of the vein graft, we may find out the methods ofpreventing restenosis of the vein graft. The animal model of the V-V graftcan help to understand the mechanism of restenosis of the vein graft.
Objective To observe the inhibitory effects of local co-transfection of tissuetype plasminogen activator(tPA) gene and proliferating cell nuclear antigen antisense oligodeoxynucleotides(PCNA-ASODN) on the intima proliferation and restenosis of autograft artery in rabbits. Methods One hundred and twenty male Zelanian rabbits were randomly divided into four groups(n=30, in each group): control group, PCNA-ASODN group, tPA group and tPA+PCNAASODN group. The left and right external iliac arteries (length 1.0 cm) were transplanted reciprocally. The transplanted arteries were respectively soaked in lipofection, PCNAASODN, pBudCE4.1/tPA and pBudCE4.1/tPA+PCNA-ASODN solution about 15 minutes. The transplanted arteries were sutured with 9-0 sutures soaked in PCNA-ASODN and pBudCE4.1/tPA solution. Each group were divided into five subgroups(n=6, in each subgroup) according to the sacrifice time (3 d, 7 d, 14 d, 28 d and 56 d after operation). On every sacrifice time point, the vascular specimens were harvested. The thrombocyte assembling and thrombus forming lining vessel wall were observed by scanning electron microscope. The pathological morphology of transplanted arteries were observed under microscope(HE). The intimal areas and stenosis ratio(%) of transplanted arteries were calculate and analyzed statistically among groups by computer system. The mRNA expression of tPA gene in transplanted ressel wall was detected with vevere transcriptionPCR(RT-PCR). The number of PCNA positive cells in transplanted vessel wall was counted by SP immunochemisty.Results The mRNA expression of tPA gene in the transplanted vessel wall in tPA and tPA+PCNA-ASODN groups was higher than that of the other two groups(P＜0.01).The number of PCNA positive cells in the transplanted arteries in PCNAASODN, tPA and tPA+PCNAASODN groups were significantly lower than that of control group(P＜0.05，P＜0.01). The intimal areas and degrees of luminal stenosis of PCNAASODN, tPA and tPA+PCNAASODN groups were lower than those of control group(P＜0.05，P＜0.01), and those of tPA＋ PCNA-ASODN group were lower than those of PCNA-ASODN and tPA groups(P＜0.05). Scanning electron microscopy showed that there were a few thrombocytes lining the vessel wall of tPA group and tPA+PCNAASODN group and no thrombus, whereas there were abundant thrombocytes and thrombi lining the vessel wall of the control group. Conclusion Co-transfection of tPA gene and PCNA-ASODN can effectively inhibit the proliferation of VSMC, hyperplasia of intima and restenosis of transplanted artery.
Abstract: Coronary artery bypass grafting (CABG) is one of the conventional treatments of coronary artery disease. Though the artery grafts have its own superiority, autologous great saphenous vein is still commonly used. Ten years after operation, half of the vein grafts will be occluded and half of the remainder will often undergo severe pathological conditions. The poor long term patency of vein grafts has become the bottleneck of the efficiency of CABG. The restenosis of vein grafts resulting from neointima and atherosclerosis has become an urgent problem waiting to be resolved. As the study on the molecular mechanism and pathophysiology of the vein grafts disease develops, many therapeutic schedules have been made, including drug therapy, external stent, expanding solution and gene therapy. By contrast, gene therapy has a broader prospect. This article will have a review on the prevention of restenosis of the vein grafts after CABG.
ObjectiveTo investigate the effectiveness of epidermal growth factor receptor antagonist (AG-1478) on chronic proliferative cholangitis (CPC), so as to investigate new treatment approach for hepatolithiasis associated with CPC. MethodsForty-six SD rats were divided into 5 groups: CPC model group (n=10), only made models. AG-1478 treatment group (divided into 3 mg/kg， 6 mg/kg， and 12 mg/kg groups, n=10 per group), the common bile ducts in CPC animal model received an intralumenal administration of AG-1478 at the meantime of modeling, followed by intraperitoneal AG-1478 injection of 1.5 mg/(kg·d) for 7 days. Sham operation group (SO group, n=6). Subsequently, histopathological observation, immunohistochemistry, real time PCR， and Western blot were used to evaluate the mRNA expression and influence of AG-1478 on the hyperplasia （EGFR， ki-67， BrdU， collagen Ⅰ protein） and lithogenic potential (Mucin 5AC) of CPC. ResultsCompared with CPC model group, the expressions of EGFR, ki-67， and BrdU were obviously decreased in the AG-1478 treatment group. Also, the inhibition of hyperplasia of biliary epithelium and collagen fibers were confirmed by histopathological observation. Additionally, the expressions of Mucin 5AC mRNA and collagen Ⅰ protein remarkable decreased in the AG-1478 treatment group (Plt;0.05). Conclusions EGFR inhibitor (AG-1478) could shows inhibitory effectivenss on the CPC-mediated hyperplasia and lithogenic potential, and therefore holds promise as the new treatment approach for CPC.
Objective To find out the follow-up results of early in-stent restenosis (ISRS) and develop effective way to improve clinical treatment and precaution of restenosis. Methods The data from a registry of 51 consecutive patients who underwent elective carotid artery angioplasty and stenting （CAS） at our institution between Jan. 2003 and Sept. 2005 were retrospectively reviewed. Complete data for 37 of these patients were available. All patients underwent duplex ultrasound scanning in follow-up period, which was used to determine the degree of restenosis. Results CAS was performed in 37 patients， 8.1% (3/37) were women. Mean age was (70.5±5.9) years. Mean time of follow-up was (12.2±7.7) months. Sixteen (43.2%) caces of ISRS （gt;30%） were found by color duplex ultrasound scanning， but only 1 (2.7%) ISRS was found gt;50%; 3 female patients had minor ISRS. Among all factors, female patients had higher incidence of ISRS than male (P=0.038); balloon-expanding after stenting and accompanying with other artherosclerosis of periphery vessel had correlation about ISRS （P=0.037, P=0.016）. Conclusion The severe restenosis rate is acceptable. Female patients were more likely to have ISRS. Balloon-expanding maybe have effect on reducing incidence of ISRS and controlling artherosclerosis was helpful.
【Abstract】Objective To investigate the irradiating effect of low intensive microwave (LIM) on pathological process of blood vessel restenosis(RS) and assess the probability of LIM irradiation to prevent was used RS.Methods Fortyfour male healthy New Zealand rabbits were randomly divided into 2 groups. Fogarty catheter traumatize to the tunica intima of iliac artery so as to establish RS models. Two thousand four hundred and fifty MHz microwave with different power of 2 ,5 and 10 mW/cm2 was used, locally to irradiate EIA in irradiating group (1 h/d). Specimens were obtained at different time of 3,7,14 and 28 d after operation. Morphological changes of tissues were observed with HE and EF staining and the area of tunica intima, tunica media and the rate of cavity stenosis were analyzed with image analysis system; apoptosis was detected with TUNEL; phenotype and microstructure of VSMC were observed with TEM. Results After microwave irradiating, inflammatory reaction in early period was suppressed, mural thrombus decreased, the proliferation and migration of VSMC depressed, the area of tunica intima and the rate of cavity stenosis obviously reduced comparing with the control group (P＜0.01). The rate of apoptosis cells showed that there were no obvious differences among each group on 3 d after operation (Pgt;0.05). At other different time, however, the rate of apoptosis cells in irradiating groups obviously increased than that of the control group (P＜0.01), particularly in the one with power of 5 mW/cm2 .The number of synthesis form VSMC in the control group occupied (93.50±3.45)% of the total number of VSMC on 14 d after operation. Most of VSMC appear contractile in irradiating group in which a lot of morphological changes of apoptosis in fibroblast and VSMC existed.Conclusion LIM irradiation could obviously prevented from pathologic procedure of RS. After LIM irradiating, inflammatory reaction in early period is suppressed, the proliferation and migration of VSMC depressed. LIM irradiation promotes cell apoptosis, effectively prohibites the occurring and development of RS. LIM irradiation has had relationship between quantity and effect, power span to effectively prohibit RS, particularly in the one with power of 5 mW/cm2.
Abstract: Objective To investigate the effect of keeping implanted vein graft from restenosis by local application of paclitaxel. Methods Ninetysix New Zealand rabbits were randomly divided into three groups, control group (n=32), group Ⅰ(n=32), group Ⅱ(n=32). The vein graft stenosis model was made in all rabbits. In group Ⅰand group Ⅱ, 1μg and 8μg of paclitaxel was applied locally in pluronic gelatin respectively. There were no local treatment in control group. Grafts were harvested at 1, 2, 4, and 6 weeks and underwent morphological analysis as well as immunohistochemical analysis. Results The intimal thickness in group Ⅱ were significantly decreased compared to those in control group at 1,2,4, and 6 weeks after operation (30.10±4.50μm vs. 48.20±9.16μm, 40.70±6.91μm vs. 54.20±8.67μm, 54.70±7.11μm vs. 68.60±13.72μm, and 68.70±8.24μm vs. 76.40±12.98μm, Plt;0.05). The CD8 positive cells and metallothionein positive cells in group Ⅰand group Ⅱ were significantly decreased compared to those in control group (Plt;0.05). Conclusion The results suggest that perivascular application of paclitaxel inhibits neointimal hyperplasia of vein grafts in a rabbit model, and paclitaxel may have a therapeutic potential for the treatment of vein graft disease.
ObjectiveTo investigate the risk factor for restenosis of esophageal anastomosis stricture after esophageal cancer operation. MethodsWe retrospectively analyzed the clinical data of 83 patients including 61males and 22 females at age of 58.9(41-81) years with esophageal anastomoic stricture after esophageal cancer operation between January 2002 and December 2013. According to whether the patients developed to restenosis or not, the statistical test and logistic regression was conducted to analyze the risk factors for restenosis. ResultsIn the 83 patients with esophageal anastomoic stricture after esophageal cancer surgery, 35 patients (42.2%) experienced restenosis within the following-up of 1 year. The result of logistic regression analysis indicated that restenosis appeared in 3 months (Wald value=23.3, P < 0.001), the interval between two subsequent sessions of more than 4 weeks at each esophagus dilatation(Wald value=4.8, P=0.029) and the stricture diameter of less than 12 mm after dilation (Wald value=5.8, P=0.016) are the independent risk factors for restenosis in esophageal anastomotic stricture. ConclusionFor the patients with esophageal anastomoic stricture after esophageal cancer operation, we believe that it's conducive to reduce esophageal restenosis if the interval between dilations is within 4 weeks and the diameter of stricture after dilation can reach above 12 mm.
Abstract:Objective To evaluate the effect of external stents on preventing vein graft neointima formation and medial thickening with non-restrictive macro porous polyester stent around porcine vein grafts. Methods Studies were performed by using ＂white race＂ pigs （n= 10） weight 25-30 kg. All the animals underwent bilateral saphenous vein into carotid artery bypass grafting. In each animal, a maeroporous stent was placed around a graft on one side and a control （unstented） graft on the opposite side. The polyester stent was shaped to cover both anastomoses completely. The size of the stem allowed unrestricted expansion of the graft in initial response to arterial pressure. After 35 days of surgery,all animals were taken to remove the grafts. Graft wall dimensions, platelet- derived growth factor （PDGF） expression and cell proliferation using proliferating cell nuclear antigen （PCNA） were measured on histological sections. Results Stents significantly reduced neointimal thickening （0. 4872 ± 0. 0706 mm vs. 0. 2259± 0. 0553mm,P〈0. 01）and medial thickening （0. 6246±0. 0859mm vs. 0. 4201±0. 0615mm,P〈0. 01）. Stents significantly reduced the percentage of cells expressing PDGF and PCNA. Media, intimal PCNA index was reduced from 7. 980/00± 4. 060/00 to 3.35±0.95%（P〈0.01）, PDGF index was reduced from 9.47%±5.35% to 2.67%± 0.97% （P 〈0. 01）. Conclusion External non-restrictive polyester stent can significantly inhibit neointimal formation and medial thickening, and may prevent late vein grafts restenosis.
ObjectiveTo evaluate the effect of low power red laser illumination on the intimal proliferative response in vein graft models.MethodsAutogenous vein graft models were established in 80 rats by transplanting jugular vein to carotid artery by end to end anastomosis, and were randomized into two groups: control group (graft nonilluminated), laser illumination group (0.9 J/cm2).The grafted veins were harvested at 3,7,14 or 28 day respectively after operation. IH (intimal hyperplasia) and SMC (smooth muscle cell) proliferations were pathologically and immunohistochemically observed and analyzed by computer digitizing system. ResultsThere were no significant differences in the intimal average thickness and the areas of lumen between two groups for 3 day. Laser group was significantly lower than the control in both the intimal average thickness and the stenosis of lumen at 7 day,14 day and 28 day (P＜0.05).Immunohistochemical analysis of PCNA indicate the decreased positive cell in laser group compared with the control group (P＜0.01).ConclusionThese preliminary results demonstrate that a certain density of low power red laser illumination in vein graft inhibits SMC proliferation and neointimal hyperplasia in rat.