Vascular closure staples reduce intimal hyperplasia in prosthesis implantation

Background: Vascular surgery, like the various other surgical specialities, has seen an increasing demand toward faster and more minimally invasive procedures. One such need is to create a reliable vascular anastomosis that is faster, easier and less damaging to the tissue. The vascular closure staples (VCS*) device provides such characteristics but, to date, no studies have investigated its effectiveness in reducing intimal hyperplasia when used for vascular prosthesis implantation. The present study evaluated its effectiveness compared with suturing of a graft in vascular prosthesis implantation. Methods: Twelve female Merino sheep underwent gelatin sealed Dacron patch graft implantation into the left and right common carotid artery. Grafts were randomly allocated so that one carotid artery and graft was anastomosed using sutures and the other with VCS*. The two techniques were compared for operation time, clip/suture numbers and blood loss during the implantation procedure. After a 4‐week period, the sheep were killed and the grafts were harvested for intimal hyperplasia (IH) assessment. Results: There was a significant reduction in the amount of IH seen in the VCS* group (mean ± SD: 0.278 ± 0.079 mm²/mm) when compared with the sutured group (0.575 ± 0.331 mm²/mm) (P < 0.05). There was also significant reduction in anastomosis time (mean ± SD: 14 ± 4.4 min) and fewer points of contact (23 ± 1.4) using the VCS* compared with suturing (22 ± 3.2 min, P < 0.01; 27 ± 3.3, P < 0.05, respectively). Conclusions: In this model, the VCS* shows several distinct advantages over suturing with significant time saving at operation and, most importantly, the reduction of IH seen at 1 month.     

Colchicine inhibits intimal hyperplasia and leukocyte VEGF expression in dogs

BACKGROUND: Restenosis due to intimal hyperplasia following percutaneous transluminal angioplasty limits its long-term efficacy. We evaluated the effect of colchicine on the development of intimal hyperplasia following balloon angioplasty and on the vascular endothelial growth factor (VEGF) expression in leukocytes. MATERIAL AND METHODS: Adult dogs underwent balloon angioplasty of the right iliofemoral artery. Group 1 served as control, while groups 2 and 3 (six animals per group) received 0.1 and 0.5 mg/kg/d of colchicine p.o., respectively, starting 2 d before angioplasty and continued for 14 d. Before angioplasty and at day 14, blood samples were collected for drug toxicity analysis and the determination of leukocyte expression of VEGF. Animals were euthanized and iliofemoral arteries were perfusion fixed in situ and processed for histological and morphometric analysis. RESULTS: Balloon angioplasty without colchicine resulted in 446% (P < 0.001), 111% (P = 0.7), and 267% (P < 0.001) increase in intimal and medial thickness and intima/media ratio compared with contralateral uninjured iliofemoral arteries. Low-dose and high-dose colchicine resulted in 32% and 58% reduction in intima/media ratio, respectively (both P < 0.001). VEGF expression in leukocytes of control group was up-regulated (40%), but was down-regulated by 12% and 55%, respectively, in low-dose and high-dose colchicine groups at 2 wk after angioplasty compared with preangioplasty expression. The results of complete blood count and serum transaminases and creatinine were within normal range. CONCLUSION: This study demonstrates that oral colchicine for 2 wk significantly reduces intimal hyperplasia following balloon angioplasty in dogs through down-regulation of leukocyte VEGF expression and without apparent toxicity.     

A novel mouse model of autologous venous graft intimal hyperplasia

BACKGROUND: To investigate the molecular mechanism of autologous venous graft intimal hyperplasia, a mouse model is needed. Currently only vein to carotid artery mouse models are available and are hampered by a high thrombosis rate. We hypothesized that operating on the aorta would lead to intimal hyperplasia with decreased risk of thrombosis. MATERIALS AND METHODS: In C57BL/6J mice, the left external jugular vein was grafted into the infrarenal abdominal aorta by end-to-end anastomosis with 11-0 Ethilon. Grafts harvested at 1, 2, 4, 8, and 16 weeks postoperatively were subjected to histological and immunohistochemical analysis. RESULTS: Thirty-one of 35 mice survived; 2 mice were sacrificed secondary to thrombosis. The percentage lumen narrowing (+/-SE) was 7.8 +/- 0.3, 16.4 +/- 0.9, 19.2 +/- 0.9, 22.3 +/- 0.8, and 23.9 +/- 1.6% at 1, 2, 4, 8 and 16 weeks, respectively. Nuclear density decreased with each successive time point. The percentage of alpha-smooth-muscle actin-positive cells within the neointima peaked at 16 weeks (53%), and the percentage of cells positive for proliferating cell nuclear antigen peaked at 2 weeks (39%). CONCLUSIONS: We thus report on a novel mouse model of intimal hyperplasia in autologous venous grafts with a low thrombosis rate. Further studies using this model, coupled with genetic and bone marrow transplantation mouse models, should lead to significant enhancement in understanding of the mechanism of intimal hyperplasia.     

Evaluation of platelet deposition and neointimal hyperplasia of heparin-coated small-caliber ePTFE grafts in a canine femoral artery bypass model

INTRODUCTION: Bypass graft failure due to acute thrombosis and intimal hyperplasia remains a major challenge in small-diameter vascular prosthetic graft reconstruction. Heparin has been shown to prevent thrombus formation and inhibit intimal antithrombotic in animal studies. In this study, we evaluated the effect of small-caliber heparin-coated expanded polytetrafluoroethylene (ePTFE) grafts on platelet deposition and intimal hyperplasia in a canine model of femoral artery bypass grafting. METHODS: Nine adult greyhound dogs underwent placement of bilateral femorofemoral artery bypass grafts with ePTFE grafts (4 mm diameter and 7 cm long). In each animal, a heparin-coated ePTFE graft was placed on one side while a noncoated graft was placed on the contralateral side which served as the control. Platelet deposition was measured by autologous (111)indium-labeling and scintillation camera imaging analysis in 24 h. The graft patency was assessed at 4 weeks following the bypass. The effect of intimal hyperplasia was assessed with histological and morphometric analysis. RESULTS: Platelet deposition on the heparin-coated grafts at 24 h was significantly reduced by 72% as compared to controls (P = 0.001). The patency rate was 44% in control grafts and 89% in heparin-coated grafts. There was a significant reduction of graft intimal hyperplasia at both proximal (0.38 +/- 0.21 mm(2)) and distal (0.19 +/- 0.06 mm(2)) anastomoses in the heparin-coated grafts as compared with proximal (1.01 +/- 0.28 mm(2)) and distal (0.42 +/- 0.01 mm(2)) anastomoses in the untreated control grafts, respectively (P < 0.05). Heparin coating significantly reduced graft neointimal hyperplasia at patent graft anastomoses by 55-72% as compared to controls. CONCLUSIONS: These data demonstrate that heparin coating of ePTFE significantly reduced early platelet deposition and inhibited anastomotic neointimal hyperplasia. Moreover, small-caliber heparin-coated ePTFE graft significantly increased graft patency in a canine femoral artery bypass model. This may represent a promising treatment strategy for improving the clinical performance of small-caliber prosthetic vascular grafts.     

Morphometric and histological changes in the vascular wall after external radiation for the prevention of intimal hyperplasia

BACKGROUND: Recent reports describe spontaneous dissections and aneurysms after coronary and peripheral artery irradiation for the prevention of intimal hyperplasia. We investigated histological changes and the vasomotor reaction in the vascular wall after external radiation for the prevention of intimal hyperplasia in rabbits. MATERIALS AND METHODS: The aorta was experimentally injured in 34 rabbits who were then assigned to one of three groups: irradiation with 20 Gy; with 25 Gy; and a control group with no irradiation. Before the arterial injury and 45 days later, vasomotor function was assessed with an intravascular ultrasound catheter. The aorta was resected for morphometric and histological studies. RESULTS: After injury and irradiation, vasomotor responses were significantly lower in the two irradiated groups (P < 0.05). Intimal thickness and the intima/media ratio were significantly lower in irradiated groups. In the irradiated group histological examination showed reduced intimal proliferation with an intact endothelium. In the 20-Gy irradiated group the vascular media contained necrotic areas, and in the 25-Gy irradiated group, severe fibrosis. CONCLUSION: After arterial injury, external irradiation at 20 and 25 Gy effectively reduces aortic intimal and medial thickening. Histological changes include recasting with necrosis and fibrosis causing a decreased vasomotor response. Further investigations are needed to confirm medial necrosis and replacement with fibrosis. Because the irradiation doses in this study match those currently used and also recommended for experimental and clinical use, if confirmed in humans parietal recasting might possibly explain the reported spontaneous dissections and aneurysm formation after irradiation.     

Inhibitory effect of brachytherapy on intimal hyperplasia in arteriovenous fistula

PURPOSE: To determine whether endovascular radiation can inhibit intimal hyperplasia in a swine model of hemodialysis access. MATERIALS AND METHODS: Polytetrafluoroethylene arteriovenous grafts (6 mm in diameter) were placed between the common carotid artery and the external jugular vein bilaterally in 8 pigs. Two days after the surgery, fistulography was performed. Gamma radiation (12 Gy) was delivered endovascularly to one of the grafts at the venous anastomosis by using an iridium(192) source. Thus, the other graft in each pig served as an untreated control. Fistulas were evaluated with fistulography or venography 6 week after radiation. All grafts were then harvested for histological and immunohistochemical examination. RESULTS: Seven grafts on the treated side and 5 grafts on the control side remained patent for at least 6 weeks. Angiography demonstrated that the percentage stenosis at the venous anastomosis was significantly lower for the treated group (15.9 +/- 14.1 versus 32.6 +/- 16.7%, P = 0.045). Histopathologic analyses revealed that the mean intimal area and maximal intimal thickness were significantly lower with reduced smooth muscle cell proliferation at the venous anastomosis on the treated side compared to the control side (0.68 +/- 0.30 versus 1.06 +/- 0.29 mm(2), P = 0.017, and 0.18 +/- 0.08 versus 0.26 +/- 0.07 mm, P = 0.004, respectively). The residual lumen was significantly greater for the treated group (1.59 +/- 0.42 versus 1.06 +/- 0.37 mm(2), P = 0.031). No significant differences were found in the area, nor maximal thickness in the vein either proximal or distal to the anastomosis between the two groups. CONCLUSIONS: In an animal model of hemodialysis access, brachytherapy with iridium(192) delivered 2 days after graft implantation reduces intimal hyperplasia and stenosis at the venous anastomosis. The reduced smooth-muscle cells found in the radiated veins suggests that brachytherapy may exert its effect on neointimal formation by inhibition of smooth muscle cell proliferation.     

Inhaled carbon monoxide prevents graft-induced intimal hyperplasia in swine

BACKGROUND: Arteriovenous grafts often fail due to stenosis caused by venous anastomotic intimal hyperplasia (IH) and vascular smooth muscle cell (VSMC) proliferation. We examined the effects of inhaled carbon monoxide (CO), a product of heme-oxygenase-1 degradation of heme, on IH in a porcine arteriovenous graft model. MATERIALS AND METHODS: Eighteen Yorkshire pigs were divided into three groups (N = 6/group): (1) CO 100 ppm preoperatively for 1 h; (2) CO 250 ppm preoperatively for 1 h and intraoperatively; and (3) air-treated controls. Animals underwent end-to-side placement of polytetrafluoroethylene grafts connecting the common femoral artery and vein in both groins. Intimal thickness of the venous anastomosis at 30 days was measured blinded. The effect of CO on pig VSMC proliferation was studied in cell culture using [(3)H]thymidine incorporation. RESULTS: Pigs in the group receiving CO 250 ppm showed significantly less IH compared to animals in the group receiving 100 ppm and the air-treated group (267.5 +/- 21.4, 824 +/- 145.8, and 914.8 +/- 133.7 pixels, respectively, P < 0.0001). This effect was not observed when comparing the 100 ppm group to the air-treated group. COHb levels were significantly elevated in the 100 ppm and 250 ppm compared to air-treated pigs (5.8 +/- 0.47, 13.2 +/- 1.0 versus 2.3 +/- 0.11%, respectively, P < 0.001). Oxygen saturation, respiratory rate, and hemodynamics were not significantly different between the groups. CO induced VSMC growth arrest compared to air in vitro (11.9 +/- 4 versus 20.3 +/- 5 10(3) counts/min/well, P < 0.01). CONCLUSION: A single exposure to a low concentration of inhaled CO (250 ppm) confers protection against intimal proliferation of VSMCs when given perioperatively in a clinically relevant model of arteriovenous grafts. These data are the first to suggest, in a clinically relevant model, the potential role for CO in clinical applications.     

Chronological changes in morphometry and histology in the rabbit vascular wall after external radiation for the prevention of intimal hyperplasia

BACKGROUND: Although ionizing radiation has been proposed for the prevention of intimal hyperplasia in coronary and peripheral arteries, information is lacking on how irradiation affects arterial histology and neointimal smooth-muscle cell proliferation-the hallmark of restenosis. We chronologically investigated early histological changes and quantitative changes in arterial wall cell proliferation after arterial injury followed by external radiation for the prevention of intimal hyperplasia in rabbits. MATERIALS AND METHODS: The aorta was experimentally injured in 26 rabbits who were then assigned to two groups: irradiation with 20 Gy and a control group with no irradiation. The aorta was resected for morphometric and histological studies at 3, 7, 15, 30, and 45 days after experimental injury. RESULTS: Intimal thickness was reduced and the intima/media ratio was significantly lower in irradiated groups than in control rabbits. In the irradiated group histological examination showed delayed neointimal proliferation with an intact endothelium. In the 20-Gy irradiated group the vascular media at 7 days contained necrotic areas and delayed fibrosis with calcifications. There was no statistical difference between the number of proliferating cells in the irradiated groups and the control group. Proliferating cells reached maximum numbers later in irradiated groups than in control rabbits (45 days versus 3 days). CONCLUSION: After arterial injury, external irradiation at 20 Gy effectively reduced aortic neointimal thickening. Irradiation-induced histological changes include recasting with rapid necrosis and delayed fibrosis. Radiation-induced parietal recasting with necrosis, fibrosis, and calcifications might worsen in time. Although irradiation after arterial injury leaves proliferative smooth-muscle cells within the arterial wall quantitatively unchanged in the early days after the procedure, it then induces a delayed reaction (observed over 45 days in our study). Whether neointimal hyperplasia is merely delayed or will ultimately develop causing restenosis awaits confirmation from experimental and clinical studies with a long-term follow-up.     

Rapid,arteriovenous graft failure due to intimal hyperplasia: a porcine,bilateral, carotid arteriovenous graft model

BACKGROUND: The loss of patency constitutes the major complication of arteriovenous (AV) polytetrafluoroethylene hemodialysis grafts. In most cases, this graft failure is due to intimal hyperplasia at the venous outflow tract, including proliferation of vascular, smooth muscle cells and fibroblasts with deposition of extracellular matrix proteins. Thus far, procedures developed for improving patency have proven unsuccessful, which can be partly explained by the lack of relevant animal models. For this purpose, we developed a porcine model for AV graft failure that will allow the assessment of promising therapeutic strategies in the near future. MATERIALS AND METHODS: In 14 pigs, AV grafts were created bilaterally between the carotid artery and the jugular vein using expanded polytetrafluoroethylene. Two, 4 or 8 weeks after AV shunting, the grafts and adjacent vessels were excised and underwent histologic analysis. RESULTS: From 2 weeks onwards, a thick neo-intima developed at the venous anastomosis, predominantly consisting of alpha-actin-positive vascular smooth muscle cells (VSMC). Intimal area increased over time, coinciding with a decreased graft flow. Grafts remained patent for at least 4 weeks. At 8 weeks, patency rates declined to less than 50% due to thrombus formation superimposed on progressive neo-intima formation. CONCLUSIONS: Implantation of an AV graft between the carotid artery and jugular vein in pigs causes a rapid neo-intimal response, accompanied by a loss of patency of 50% at 8 weeks after surgery. This model offers a suitable tool to study local interventions aimed at the improvement of AV graft patency rates.     

吡格列酮对静脉旁路血管内膜增生的影响

目的 探讨吡格列酮(PIO)对静脉旁路血管内膜增生的影响及可能机制.方法 将32只SD大鼠随机分为2组,分别予(3mg·kg-1·d-1)的PIO或盐水灌胃,1周后行自体右颈外静脉-颈总动脉移植术,术后持续给药2、4周后取静脉旁路血管.应用图像分析软件计算内膜增厚情况,westernbolt检测ERK1/2激活情况.体外培养人大隐静脉平滑肌细胞,采用CCK-8法检测细胞增殖,TUNEL法检测细胞凋亡.结果 与同期对照组相比,PIO明显减少术后2周[(8.56±1.64)μm对(25.44±0.89) μm,P＜0.01]和4周[(10.51 ±1.47) μm对(35.69±1.07) μm,P＜0.01]静脉旁路血管内膜厚度,抑制ERK1/2活性.PIO显著抑制PDGF-BB诱导的细胞增殖并促进细胞凋亡.结论 PIO能有效抑制静脉旁路血管术后内膜增生,可能与其下调ERK1/2活性,抑制血管平滑肌细胞增殖并促进凋亡密切相关.     

Intimal hyperplasia: The permeation of serum-derived substance into the arterial autovein graft under abnormal blood flow

The etiology of intimal hyperplasia in autogenous vein grafts used for arterial replacement was experimentally studied in dogs. We previously developed an experimental model, which mimicked a human extremity with poor run-off of peripheral arteries. This model characterized the abnormal flow by a weak fluctuation of wall shear stress at the site adjacent to the vessel wall. In this model we found that an autogenous vein implanted into the femoral artery under such abnormal flow conditions exhibited remarkable intimal thickening; 200–400 μm at 1 month and 300–500μm at 6 months. A fluorescence microscopic study revealed that Evans blue-albumin complex entered the inner wall of vein grafts transplanted in abnormal flow conditions until about 2 weeks after implantation, after which further permeation was no longer observed. A similar observation was made in the fibrinogen distribution of subendothelial tissue. These results showed that abnormal flow conditions enhance the permeation of certain substances into immaturely repaired intimal tissues of autovein grafts. This phenomenon is thought to be responsible for the proliferation of smooth muscle cells, leading to hyperplasia of autovein grafts.     

The biologic fate of Dacron double velour vascular prostheses —A clinicopathological study—

Thirty-one Dacron double velour prostheses removed from 16 patients were studied microscopically in order to elucidate the changes they underwent following implantation. The process of incorporation was divided into three phases. In the initial phase, immediately following the implantation, the prostheses became surrounded by a fibrin meshwork. In the organizing phase, which sets in 10 weeks after the implantation, there was an external fibrous capsular formation around the initially fibrin-infiltrated grafts. There was also fibroblastic ingrowth and granulation formation among the interstices and the prostheses showed firm adhesion to the surrounding tissues. One year following the implantation, after most of the luminal surfaces had been covered with collagen tissues, the cellular infiltration subsided and the graft passed into the stable phase. Foreign body giant cells and lymphocytes were seen throughout the study period. These prostheses were then compared with other prostheses which do not have velour structures. The nonvelour grafts showed less adhesion to the surrounding tissues. Microscopically, cellular reaction and collagenous ingrowth were also less. The velour surface thus seems to stimulate granulation ingrowth and to contribute to the firm adhesion of the graft to the surrounding tissues. This firm adhesion enhances resistance to infection and is considered safer in case of suture aneurysm formation.     

CORMs protect endothelial cells during cold preservation,resulting in inhibition of intimal hyperplasia after aorta transplantation in rats

Allograft vasculopathy is the leading cause for chronic transplant loss. We investigated if the addition of carbon monoxide releasing molecules (CORMs) to the preservation solution would protect the endothelium from cold preservation injury in an aortic transplantation model. In particular, we tested if CORM preserve vascular functioning and limit neo‐intima formation following cold preservation (Cp). Abdominal aortas from Lewis or Fisher rats were subjected to Cp in University of Wisconsin (UW) solution to which 50 μm of CORM‐3 was added or not. Hereafter, whole mount staining, acetylcholine mediated vasorelaxation (AMV) and aortic transplantation was performed. In vitro CORM‐3 protected human umbilical vein endothelial cells from Cp injury and prevented denudation and intercellular gap formation in aortic grafts. Cp resulted in loss of AMV of aorta segments. By contrast, AMV was preserved after the addition of CORM‐3 during Cp. Two months after transplantation Cp of aorta grafts resulted in an increased adventitial remodelling and neo‐intima formation. This was significantly blunted by CORM‐3 in syngeneic recipients. Our study demonstrates that addition of CORM‐3 to UW solution prevents endothelial damage, thereby maintaining vascular function directly after cold preservation. Hence, our findings might offer a novel strategy to prevent vascular damage during CP.     

Microscopic and immunohistological studies on intimal hyperplasia of the arterially implanted autovein graft and its anastomosis in dogs

The fate of intimal hyperplasia of arterially implanted autovein bypass grafts and their distal end-to-side ananstomoses in dogs was studied microscopically and immunohistologically. The bypass grafting was done under conditions of abnormal blood flow and high peripheral resistance. Intimal hyperplasia of the graft first became evident 7 days after implantation and the thickness increased to about 500 m 3 months or more after the implantation. The intimal hyperplasia was related to an active proliferation of smooth muscle cells which proved positive for alpha-smooth muscle actin staining. Moreover, it was more dominant at the toe and heel of the anastomosis and moderately apparent on the floor of the host artery. The constituent elements of the hyperplastic intima at the anastomosis were fibroblast-like cells and extracellular collagen fibers which were negative for alpha smooth muscle actin staining. This study revealed that the features of intimal hyperplasia at the distal anastomosis in autovein bypass grafting differed from those of the implanted autovein graft itself; the former being related to excessive proliferation of fibroblasts and collagen fibers while the latter displayed an active proliferation of smooth muscle cells.     

The effects of Batroxobin on the intimal hyperplasia of graft veins

Background

To investigate the effects of Batroxobin (BX) on the intimal hyperplasia of graft veins.

Methods

Twenty dogs were evenly divided into 2 groups. The femoral veins were grafted into the femoral artery by microsurgery, and the experimental group was treated with BX (0.1 BU/kg/48 hours). The serum level of endothelin-1 (ET-1) was detected 2 weeks after operation. Computer image analysis system was performed to calculate the cross-sectional area of neointima and media in the vein grafts 8 weeks after operation. Immunohistochemistry method was performed to identify proliferating cell nuclear antigen (PCNA) and c-Myc.

Results

The experimental group had a lower level of serum ET-1 than the control group (P < .01), and both intimal hyperplasia and media thickness of graft veins were reduced by BX in comparison with the control group (P < .05). C-Myc expression was higher in the control group than in the experimental group (P < .01). The PCNA expression in the experimental group was significantly lower than the control group (P < .05).

Conclusions

These findings suggested that BX could inhibit intimal hyperplasia through suppressing cell proliferation activity.     

Ionizing radiation to prevent arterial intimal hyperplasia at the edges of the stent: induces necrosis and fibrosis

BACKGROUND: Although ionizing radiation has been proposed for the prevention of intimal hyperplasia in coronary and peripheral arteries in multicenter clinical trials, information is lacking on how irradiation affects arterial histology after stenting and especially how it affects the edges of the stent. We investigated intimal hyperplasia recasting with histological changes in arterial wall at the edges of the stent after arterial stenting followed by adequate external radiation for the prevention of intimal hyperplasia in pigs. MATERIALS AND METHODS: The aorta was experimentally stented in 30 pigs who were then assigned to two groups: irradiation with 20 Gy and a control group with no irradiation. The aorta was resected for morphometric and histological studies 6 weeks after procedure. RESULTS: Intimal thickness was reduced and the intima/media ratio was significantly lower in irradiated groups than in control pigs. In the irradiated group histological examination at the edges of the stent showed thin neointimal proliferation with an intact endothelium. In all sections analyzed in the 20-Gy irradiated group the vascular media at 45 days contained necrotic areas and fibrosis with calcifications. CONCLUSIONS: After arterial injury, adequate ionizing radiation effectively reduces neointimal thickening. Irradiation-induced histological changes include previously undetected recasting with necrosis and fibrosis at the arterial edges of the stent. The parietal recasting we observed in animal arteries irradiated at high doses is unclear and a cause of concern especially after clinical spontaneous dissection was recently reported. The use of ionizing radiation for the prevention of arterial restenosis awaits confirmation with a long-term follow-up including specific experimental histological analyses.     

Cigarette smoke increases intimal hyperplasia and homocysteine in a rat carotid endarterectomy

BACKGROUND: Homocysteine and smoking are independent risks for CVD; however their importance in post-CEA intimal hyperplasia is unclear. We performed a CEA in rats exposed to cigarette smoke with the hypothesis that smoking would increase intimal hyperplasia that may be associated with an elevated serum homocysteine. Folic acid (FA) and the homocysteine metabolic enzymes MTHFR and CBS were used to test for the significance of homocysteine elevation. MATERIALS AND METHODS: Rats underwent an open CEA. N = 13 rats received smoke exposure 2 weeks prior, and 2 weeks post-CEA and N = 12 received no smoke. Each group was divided into either control or an FA-added diet resulting in four groups. Rats were sacrificed at 2 weeks post-CEA; liver, urine, blood, and carotid arteries samples were obtained. RESULTS: Smoked rats had increased urinary peak and trough cotinine levels versus non-smoke rats, which decreased with FA. Smoke exposure increased intimal hyperplasia versus non-smoke controls by nearly 120% (57.8 +/- 6.2 versus 26.8 +/- 5.4% luminal stenosis, P = 0.005). Smoke-exposed rats had an increased serum homocysteine versus non-smoke controls (8.3 +/- 0.8 versus 5.7 +/- 0.8 microm, P = 0.014). Smoked rats given FA had decreased serum homocysteine compared to the smoke group. Along with reductions in homocysteine, FA eliminated the increase in intimal hyperplasia seen with smoke exposure (33.5 +/- 6.1 versus 57.8 +/- 6.2% luminal stenosis, P = 0.03). CBS activity decreased in smoked rats by nearly 20% versus non-smoke rats. FA supplementation in smoked rats both (1) increased CBS activity and (2) decreased MTHFR compared to control non-smoke-exposure levels. CONCLUSION: Smoking increases plasma homocysteine and post-CEA intimal hyperplasia. This suggests homocysteine has an etiological role in the intimal hyperplasia increase observed with smoking, since both were negated with FA.     

An appropriately sized soft polyester external stent prevents enlargement and neointimal hyperplasia of a saphenous vein graft in a canine model

Although the efficacy of external stents for vein grafts in coronary artery bypass grafting has been recognized, the ideal diameter and material of the stent remain controversial. We created a new external stent made of soft polyester mesh and performed an animal experiment using canines. Bilateral saphenous vein grafts were interposed in the bilateral common carotid artery of 10 beagles. The grafts in the left carotid artery were designated as the control group, and those in the right rolled by a soft polyester mesh external stent were designated as mesh group. Two of the 10 animals were sacrificed due to severe wound infection. The other eight were observed by echography for 6 months, and then grafts were extracted and thickness of the neointima of the grafts was measured. The control group showed 146% ± 26% postoperative enlargement of the internal diameter of the vein grafts after 6 months, whereas the mesh group showed only 115% ± 15% after the same duration (P = 0.0003). The median thickness of the neointima in the mesh group (170 µm [range: 150–190]) was significantly thinner than that in the control group (260 µm [range: 220–310], P < 0.0001). Some degree of correlation between the thickness of neointima and proportion of enlargement was noted (r = 0.518, P = 0.0024). A soft polyester mesh external stent for vein grafts successfully suppressed the enlargement of the vein grafts and thickness of the neointima after 6 months.