Pro-UK基因抑制静脉移植物细胞增生的实验研究

目的：探讨Ｐｒｏ－ｕｋ基因对静脉桥移植物细胞增生的影响。方法：３００￣３５０ｇ Ｗｉｓｔａｒ大鼠４２只,取下双鼠颈静脉,两端阻断后,用含Ａｄｖ５－ＣＭＶ／Ｐｒｏ－ＵＫ质粒（治疗组,２１只）的溶液扩张静脉,使溶液在静脉 腔内滞留３０分钟降温末然后置于同一大鼠的颈总动脉。术后２８天,取静脉移植物行尿激酶原活性测定,观察Ｐｒｏ－ＵＫ表达（２６５ｉｕ／ｇｔｉｓｓｕｅ）,对照组未测到Ｐｒｏ－ＵＫ活性。虽然两     

Inhibition of subintimal hyperplasia of autologous vein bypass grafts by nimodipine in rats: a placebo-controlled study.

An arterial bypass may be required for the management of neoplastic or cerebrovascular disease. When an arterial graft is not suitable, autologous vein grafts are the most commonly used conduits; however, as many as 20% of the vein grafts used in vascular surgery may occlude as a result of subintimal hyperplasia. Although the mechanism initiating subintimal hyperplasia remains unclear, it is known that subintimal hyperplasia is dependent upon smooth muscle cell proliferation and migration from the media to the intimal layer. The present study focused on the prevention of smooth muscle cell proliferation using a calcium antagonist. Forty rats received an autologous vein bypass graft from the jugular vein to reconstruct the abdominal aorta. They were randomly divided into two groups of 20 rats each. Animals in the treated group received a calcium antagonist (nimodipine), and those in the control group received a placebo. Nine months after grafting, the group receiving the calcium antagonist presented no or only slight sub intimal hyperplasia as compared with the placebo-treated group (P less than 0.001). These data suggest that a calcium antagonist could be used for the prevention of venous graft disease.     

Capillary and venule proliferation in the healing process of Dacron venous grafts in rats.

A woven, noncrimped graft (made of Dacron and coated with an elastomer) that was 1.5 mm in diameter and 15 mm long was capable of replacing the vena cava in rats. The elastomer mixture consisting mainly of silicone rubber was necessary to bond the woven Dacron fibrils of the woven graft to prevent fraying at the anastomoses and bleeding through the interstices of the lightly woven, fairly high porosity (500) conduit. Sequential histologic studies showed that patency was associated with the ingrowth of small venules and the spreading of endothelial cells from each anastomosis toward the center. Small venules appeared in loose connective tissue, forming a pseudointima 12 days after grafting. This process occurred in the midportion of the graft before pannus endothelial growth covered the endothelial surface. Various thicknesses of the external polymer coat were studied for their influence on healing. None of the grafts developed a thrombus in these latter studies, and regardless of the thickness of the external elastomer, endothelial resurfacing was complete at 30 days. However, the graft with the thinnest external elastomer coating had the best-formed vasa vasorum, and the intima at both the anastomoses and midportions of the graft was significantly thinner than intima found in grafts of other composition. We conclude that this woven Dacron polygraft provides a surface resistant to early thrombosis; that healing occurs mainly by pannus ingrowth, but external and interstitial factors are also important; and that properties inherent in the polygraft wall determine the size of the residual lumen.     

Initial histopathology of the autovein graft in late occlusion after arterial reconstruction

Five patients developed local stenosis of autologous vein grafts implanted for femoro-popliteal arterial occlusive lesions. This stenosis occurred in the vein grafts 2 months to 5 years after the initial operation. Histopathologic study revealed that the stenotic segments had a thickened intima with a prominent proliferation of smooth muscle cells associated with fibrous extracellular matrix. There were no findings showing deposition of mural thrombi, as has heretofore been reported. The intimal thickening due to excessive fibromuscular proliferative response of the vein graft may possibly play an important role in the development of late graft occlusion.     

Why Do Radial Artery Grafts for Aortocoronary Bypass Fail? A Reappraisal

The reasons for the high failure rate of radial artery grafts for aortocoronary bypass (ACB) are appraised. Each of 11 dogs received four types of grafts: femoral arteries were grafted to carotid arteries, and jugular veins were grafted to femoral arteries bilaterally. One of each pair of grafts was wrapped in a plastic sheet in order to interfere with the regeneration of vasa vasorum. The grafts were examined 2 months later. The results suggest that although operative trauma and intraluminal pressure change play important roles, the thick-walled artery appears to depend more on vasa vasorum for its integrity than does the thin-walled vein. A free radical artery graft, with vasa vasorum disrupted at both ends, cannot regenerate readily from the adjacent tissue, as is the case at the ACB position, and is therefore more vulnerable to subintimal hyperplasia and occlusion than either the vein graft or the internal mammary artery graft; both of these grafts are thinner, and the internal mammary artery graft remains undisrupted at one end.     

Autologous skin graft, human dura mater and polypropylene mesh for the repair of ventral abdominal hernias: an experimental study.

OBJECTIVE: To compare primary repair and grafting with one of two materials (one biological human dura mater, and one synthetic polypropylene mesh) or autologous skin, with primary repair alone in abdominal wall hernias in rats. DESIGN: Randomised experiment. SETTING: Teaching hospital, Turkey. ANIMALS: 72 male Wistar albino rats randomised into 4 groups of 18 rats each. These were further randomly divided into subgroups of 6 each that were killed on days 15, 30,and 45 postoperatively. INTERVENTIONS: Each test material was sutured to the abdominal wall by an onlay technique. MAIN OUTCOME MEASURES: Macroscopic and microscopic appearance, and strength of the abdominal wall. RESULTS: Macroscopically, dura mater grafts lost their original shape, but polypropylene and skin did not. When completely incorporated the skin grafts had developed a new fascia. Dura mater and polypropylene induced a pronounced inflammatory reaction at all three times postoperatively, and there were significantly more fibroblasts in the dura mater group on days 15 and 30, and in the skin graft group on day 45, than in the other groups (p < 0.05). Mechanical resistance and mean breaking strength were significantly greater in the skin graft group than in the other groups at all times tested (p < 0.05). CONCLUSION: Full thickness autologous skin grafts were stronger than both human dura mater and polypropylene mesh when used to reinforce primary repairs of abdominal wall hernias in rats.     

移植损伤对移植静脉影响的实验研究

目的探讨移植静脉再狭窄的机制,明确移植损伤对移植静脉的影响。方法健康新西兰大白兔36只,随机选取一侧将股静脉翻转后移植于同侧股动脉缺损(静-动组),另一侧将同等长度股静脉截取后行原位缝合(静-静组),另取正常股静脉作为对照组(取自静-动组移植前静脉的一部分)。均于术后4周取移植静脉段,行HE染色、弹力纤维的维多利亚蓝染色观察移植静脉管壁组织学变化;增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)免疫组织化学染色观察管壁细胞增殖情况;电镜观察管壁细胞超微结构改变。结果静-静组血管壁中膜平滑肌细胞增殖,但内膜(3.50±0.41μm)、中膜(12.23±1.59μm)厚度无明显变化;静-动组内膜、中膜细胞均增殖,内膜(25.60±3.21μm)、中膜(21.30±2.47μm)厚度较对照组、静-静组均增加,差异有统计学意义(P<0.01)。对照组未见PCNA阳性细胞,静-静组内膜(5.9%±1.3%)、中膜(23.4%±3.4%)PCNA阳性细胞百分比均小于静-动组内膜(16.4%±1.9%)、中膜(36.5%±3.7%),差异有统计学意义(P<0.01)。静-静组透射电镜下可见内皮细胞扁平,游离端有绒毛样突起,细胞排列紧密,中膜平滑肌细胞增殖;静-动组透射电镜下可见内皮细胞增殖明显,增殖的内皮细胞形态不规则,细胞间隙增宽,内膜中可见大量平滑肌细胞,基底膜不完整,中膜平滑肌细胞明显增殖;对照组内皮细胞形态及排列与静-静组相似,只是中膜平滑肌细胞未见增殖。结论静脉移植后可导致血管管壁细胞增殖,如合并血流动力学变化则会发生更严重的细胞增殖和迁移,导致管腔狭窄;减少移植损伤,改善移植静脉的微循环,成为预防移植静脉再狭窄的理论基础之一;静-静移植的动物模型,有助于探寻静脉移植后再狭窄的机制。     

Intimai hyperplasia following thrombectomy versus thrombolysis in occluded vein grafts

Although the histologic effects of balloon catheter thromboembolectomy in arteries are well described, little is known about its effects on arterialized vein grafts. A chronic canine model was used to compare the intimai hyperplasia that develops following balloon catheter thrombectomy versus thrombolytic therapy when each treatment was used to open experimentally occluded reversed autogenous vein grafts. Eleven of 12 dogs survived to the time of graft thrombosis and treatment. Ten grafts in one group of animals were treated with shear force-controlled balloon catheter thrombectomy, and eleven grafts in another group of animals were treated with infusion of urokinase (average 355, 833 lU/graft). Explantation and histologic evaluation was performed 5 weeks after treatment. Data were evaluated at comparable anatomic locations. These studies demonstrated the development of intimal hyperplasia in both groups with no statistically significant differences in the intimal thickening between the two treatment groups. It is hypothesized that vessel wall damage occurs at the time of thrombosis with the adherence of thrombus to the wall, and that this may be as important in producing intimai hyperplasia as the effects of carefully performed balloon thrombectomy or lytic therapy. (Ann Vasc Surg 1997;11:559-564.)     

Influence of ischemic injury on vein graft remodeling: role of cyclic adenosine monophosphate second messenger pathway in enhanced vein graft preservation

OBJECTIVE: Endothelial injury during the harvest of saphenous vein grafts might play an important role in the development of vein graft disease after coronary artery bypass grafting. Using a murine autologous arterialized vein patch model, we tested whether the initial ischemic insult of vein grafts was linked to the later development of graft neointimal hyperplasia and whether the restoration of the cyclic adenosine monophosphate second messenger pathway would attenuate the development of neointimal hyperplasia. METHODS: A segment of the external jugular vein of a mouse was grafted onto its abdominal aorta. Three weeks after the operation, the degree of neointimal hyperplasia of the implanted graft was compared among (1) grafts without preservation, (2) grafts with 2 hours of preservation (25 degrees C) in heparinized saline, and (3) grafts with 2 hours of preservation in heparinized saline in the presence of a cyclic adenosine monophosphate analog. In addition, cyclic adenosine monophosphate contents of vein grafts and leukocyte adherence to the graft endothelium were assessed. RESULTS: Cyclic adenosine monophosphate contents were significantly decreased after 2 hours of preservation (212 +/- 8 vs 156 +/- 5 pmol/L, P < .01). The grafts preserved for 2 hours showed greater neointimal hyperplasia compared with the grafts without preservation (neointimal expansion, 68.7% +/- 9.6% vs 46.1% +/- 4.8%; P < .01). The addition of a cyclic adenosine monophosphate analog to the preservation solution significantly suppressed neointimal hyperplasia of grafts preserved for 2 hours (44.3% +/- 5.0%). Inhibiting the cyclic adenosine monophosphate-dependent protein kinase by adding Rp-cAMPS abrogated the beneficial effects. Furthermore, grafts preserved for 2 hours had significantly more leukocytes adhering to the graft endothelium 24 hours after the operation compared with nonpreserved grafts, which was significantly reduced by the cyclic adenosine monophosphate treatment. CONCLUSIONS: Ischemic insult during vein graft harvest and preservation is a key factor in the development of vein graft neointimal hyperplasia at least in part caused by the depletion of cyclic adenosine monophosphate. We conclude that stimulation of the cyclic adenosine monophosphate second messenger pathway might be a potential strategy for the prevention of vein graft disease.     

Development of a method to prevent degenerative changes of the vein graft for arterial reconstruction]

Autologous vein graft is frequently used for arterial reconstruction in vascular surgery. Its' long-term patency rate, however, is low because of the degenerative changes of the vein wall. Of the basis of our hypothesis that the degenerative changes are mainly caused by an over-distension of vein wall in arterial system, in this study, autologous vein grafts of rabbit (N = 56) were implanted in the carotid arteries. To prevent overdistension, some of the grafts were covered with prosthesis which was made of microporous, compliant biodegradable polyurethane and were compared with those without prosthesis. The integrity of the architecture of the vein wall covered with prosthesis was well preserved at 6 weeks after implantation, where the biodegradation of prosthesis induced an optimal arterialization of the vein grafts. The results indicate that this method may prevent the degenerative changes of vein wall such as fibrosis and intimal hyperplasia, which would cause poor long-term patency of vein graft used for arterial reconstruction.     

An immunocytochemical analysis of rapidly progressive atherosclerosis in human vein grafts.

Aortocoronary vein grafts are known to develop atherosclerotic plaques usually superimposed on intimal hyperplasia. The cellular characteristics of these lesions have been studied with immune cytochemical techniques and compared with those in native coronary arteries. Fifteen stenosed grafts showed concentric intimal hyperplasia characterized by massive proliferation of smooth muscle cells (HHF-35+). The subendothelial layer contained numerous T lymphocytes (UCHL-1+, MT-1+) and to a lesser extent macrophages (HAM-56+). Eleven grafts had superimposed atherosclerotic plaques characterized by atheroma but otherwise showing the same cellular constituents. The atherosclerotic plaques in the venous grafts resembled those in the coronary arteries, the main difference being the occurrence of multiple atheromas (up to 4 in a single section), the high number of T lymphocytes and macrophages related to these sites and the presence of atheromas bordering directly onto the luminal surface. It thus appears that the development of atherosclerotic plaques in vein grafts is accompanied by a similar immune inflammatory reaction as in native coronary atherosclerosis, presumably in a more aggravated form. The latter phenomenon could relate to the more enhanced and rapidly progressive nature of vein graft atherosclerosis.     

The histology of seeded PTFE grafts in humans

To define the histology of PTFE femoral-popliteal grafts seeded with enzymatically-derived endothelium, we examined light level and selected scanning electron micrographs of 20 graft biopsies. Thirteen grafts were chronically occluded and the midgraft samples had a thin lining of fibrin with scattered erythrocytes and leukocytes. One anastomotic sample showed a similar pattern, while three others had neointimal fibrous hyperplasia. Six of the seven remaining midgraft samples demonstrated confluent endothelial healing over parts of the flow surface. The cells were commonly distributed along one side of the graft as viewed in cross-section. Distribution patterns were not improved by changing from a single inoculum with two graft rotation-incubation periods to a sequential inoculation separated by a graft rotation. Circumferential distribution was achieved in one instance in which inoculation was characterized by a relatively high cell density. No luminal endothelium was seen when inoculation cell densities were very low. Smooth muscle cells and fibroblasts were not seen in the subendothelial "inner capsules" of the midgrafts. We conclude that endothelialization occurs in a high proportion of seeded PTFE grafts in humans, that the donor vein surface area should measure at least 5.25% of the inoculated graft surface, that further modifications in the seeding technique will be required to achieve consistent circumferential endothelial distribution, that subendothelial smooth muscle cell invasion is uncommon in the midgraft, but that anastomotic neointimal fibrous hyperplasia probably contributed to some graft failures.     

Infrainguinal aneurysm formation in arterialized autologous saphenous vein grafts

True aneurysm formation in arterialized autologous veins is an unusual complication. We studied a patient with 2 aneurysms occurring in the mid and distal portion of an in situ femoropopliteal bypass. The first aneurysm led to graft occlusion 4 years after the primary intervention, requiring replacement of the ectatic graft segment. The graft was still patent when the patient was examined 7 years after the primary intervention and 3 years after the first aneurysm. In the mid portion of the graft, a true aneurysm measuring 5 by 8 cm had developed. The aneurysm was replaced by a reversed segment of the contralateral greater saphenous vein. Recovery was uneventful. Advanced atherosclerotic changes with extensive intimal fibroplasia, subendothelial cholesterol deposits, and ulcerations were revealed by means of histopathology of the aneurysm wall. Atherosclerosis is considered to be the main cause of aneurysm formation in vein grafts, but a review of the literature suggests the additional etiopathogenic factors should be further investigated. (J Vasc Surg 1998;28:944-8.)     

Perivenous support reduces early changes in human vein grafts: studies in whole blood perfused human vein segments

BACKGROUND: Patency of vein grafts in coronary artery bypass grafting procedures is generally less favorable than those of selected arterial grafts. However, vein grafts still are needed in cardiac operations. It would be desirable to find measures to improve the patency of vein grafts next to antithrombotic regimens. Animal studies demonstrated that arterial pressure induces overdistention of the thin-walled vein grafts and that prevention of this overdistention with extravascular support ameliorates the arterialization process with, subsequently, more favorable patency. To evaluate whether perivenous stenting of the rather muscular human vein grafts is also beneficial, we designed an in vitro model to study the early effects of perivenous support in human vein grafts. METHODS: Seven paired segments of human vein graft obtained during coronary artery bypass grafting procedures were placed in a perfusion circuit and perfused simultaneously with autologous whole blood, with a pressure of 60 mm Hg (nonpulsatile flow). After 30 minutes of perfusion, one segment, and after 60 minutes of perfusion, the remaining segment were taken for histologic and immunohistochemical examination. In the next experiments 7 segments of human vein graft were placed in the circuit and supported with a polytetrafluoroethylene graft to prevent overdistention with 7 unstented segments as controls. RESULTS: In unsupported vein grafts perfused with autologous blood under a pressure of 60 mm Hg, a complete de-endothelialization was shown after 1 hour of perfusion. In the study vein grafts, with a perivenous polytetrafluoroethylene graft preventing overdistention (n = 7), the endothelium remained intact. Electron microscopic investigation of the media showed severe damage in the circular smooth muscle layer in the unstented group, whereas in the stented group almost no injury was found. CONCLUSION: In our in vitro closed-loop model, reproducible vessel wall changes were observed in all human vein graft specimens studied. The beneficial effect of perivenous support could also be established for the human greater saphenous vein, providing a basis for clinical application.     

Reduction of intimal and medial thickening in sheathed vein grafts.

BACKGROUND: Arterial pressures are described as an important factor in the development of graft degeneration and in reduced patency rate in vein bypass grafts. Sheathing of the graft with a pressure resistant mesh tubing might slow down this development. METHODS: Saphenous vein grafts were implanted into the carotid arteries of five pigs in order to evaluate the influence on myointimal hyperplasia of a compliant Phynox mesh tubing (a wrought Cobalt-Chromium-Nickel-Molybdenum-Iron Alloy), which surrounded autologous vein grafts that were exposed to arterial pressure. Each pig was operated on using a sheathed vein graft (biocompound-graft, a hybrid vascular prosthesis) on one side and an untreated saphenous vein on the other. RESULTS: After 4 weeks intimal hyperplastic changes were found in all histological sections. The wall thickness (medial and intimal layer) varied from 351 microm to 432 microm in the biocompound-graft and from 391 microm to 1196 microm in the native vein grafts (p < 0.05, n = 5). Severe myocytial and fibroblast proliferation was only found in the control grafts. Cellularity of the medial layer differed at sites of maximal cellular density and ranged from 11 to 12 cells in the biocompound-graft and from 17 to 18 cells per counting field in the native vein grafts (p < 0.05, n = 5). CONCLUSIONS: External support of vein grafts reduces intimal and medial layer proliferation. The findings of this study are in accordance with the results reported by other research groups.     

Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased anastomotic neointimal hyperplasia in a porcine model

OBJECTIVE: We tested the hypothesis that rapamycin coated onto, and eluted from, expanded polytetrafluoroethylene (ePTFE) grafts would diminish neointimal hyperplasia in a porcine model. METHODS: Rapamycin (also called sirolimus) was coated onto the luminal surface of 6-mm-internal-diameter thin-walled ePTFE grafts by using an adhesive polymer that allows timed release of the drug. An adhesive polymer that allows timed release of rapamycin from ePTFE was developed with commercially available chemicals and applied on 6-mm ePTFE grafts. Graft integrity was characterized by scanning electron microscopy, and rapamycin levels were quantified by using high-performance liquid chromatography. Twenty-two mongrel pigs were randomized into three groups: untreated ePTFE (n = 6), adhesive-only coated ePTFE (n = 6), or adhesive- and rapamycin-coated ePTFE (n = 10). End-to-side unilateral aortoiliac bypasses were performed by using 6-mm-internal-diameter ePTFE grafts and standardized anastomotic lengths. Unilateral end-to-side aortoiliac ePTFE grafts (6-mm internal diameter) were inserted by using polypropylene sutures, 6-0 proximally and 7-0 distally; all anastomoses were 12 mm long. All animals received aspirin (325 mg orally) daily. All animals were given oral aspirin (325 mg) daily beginning on the day before surgery. At 28 days, the animals were killed, and the grafts were explanted in continuity with the adjacent aortic cuff and the outflow iliac artery. Variables compared between groups included graft patency, distal anastomotic length and cross-sectional narrowing, and intimal thickness at the arterial-graft junction indexed to the adjacent graft thickness. Microscopic analysis was performed with hematoxylin and eosin and Masson trichrome stains on paraffin sections. A pathologist blinded to experimental groups graded sections for collagen deposition, neointima formation, inflammatory cellular infiltrates, medial necrosis, and aneurysmal degeneration. RESULTS: All animals survived until they were killed without clinical evidence of limb ischemia or graft infection. Preplanned t tests in the context of one-way analysis of variance showed no difference in outcome measures between the untreated ePTFE and adhesive-only coated ePTFE groups; therefore, they were combined in further comparisons with the adhesive- and rapamycin-coated ePTFE group. The Rapamycine eluting expanded polytetrafluoroethylene group had longer anastomoses (85.6% vs 60.6% of the initial anastomotic length maintained; P < .0001) and less cross-sectional narrowing in the outflow graft (16.2% vs 28.5%; P = .0007) when compared with the other two groups by using two-tailed Student t tests. There was no evidence of medial necrosis or aneurysmal degeneration. All patent grafts had complete endothelialization on hematoxylin and eosin sections. Rapamycin was detectable and quantifiable in the arterial wall at 28 days after implantation. CONCLUSIONS: Rapamycin can be coated onto and eluted from ePTFE by using a nonionic polymer and a simple coating technique. At 4 weeks after implantation, the rapamycin-eluting ePTFE grafts demonstrate gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with non-drug-eluting ePTFE. Four weeks after implantation in a porcine model, rapamycin-eluting ePTFE grafts demonstrated gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with untreated and adhesive-only coated ePTFE grafts. CLINICAL RELEVANCE: Rapamycin-eluting ePTFE grafts decrease neointimal hyperplasia in a porcine model. Further studies are needed to evaluate whether patency will be improved. Rapamycin-eluting ePTFE grafts may allow the use of prosthetic grafts in situations in which autologous vein is unavailable and in which neointimal hyperplasia is pronounced, such as in small-diameter (<6-mm) vessels typical of infrapopliteal interventions.     

Vein to artery grafts. A quantitative study of revascularization by vasa vasorum and its relationship to intimal hyperplasia.

Iliolumbar vein to iliac artery grafts were placed in 40 rats by microsurgical technique. Groups of animals were perfused with fixative at eight intervals between one and 20 weeks after operation, and sections of the graft and control arteries (the opposite iliacs) were analyzed microscopically. The revascularization of the graft by capillaries commenced within the first postoperative week. The level of vascularity (capillaries per cross-sectional mm2) increased during the first four weeks, maintained a constant level and declined after week 16. The grafts of the 17--20 week group were substantially less vascular than the earlier groups. Intimal thickening commenced at three to four weeks after operation, i.e. during the period of increasing graft vascularity. The mean intimal proportion of the graft was 14% at four to five weeks and at 17--20 weeks was 35% of the cross-sectional area of the graft wall. However, the actual thickness of the intima did not increase significantly with time, rather the whole graft wall tended to become thinner. At 17--20 weeks grafts which showed a high degree of intimal thickening had significantly fewer capillaries within their walls. Quantitative evidence is presented to suggest that the continued growth of the graft intima may not be supported by a similar increase in the number of vasa vasorum. Therefore, it is suggested that the reduced level of vascularity in grafts with hyperplastic intimae may form an ischemic basis for degenerative changes which are known to take place in some long-term grafts.     

Saratin,an inhibitor of collagen-platelet interaction,decreases venous anastomotic intimal hyperplasia in a canine dialysis access model

Prosthetic dialysis access thrombosis and/or stenosis is the most common cause of graft impairment or loss and is primarily attributed to venous outflow stenosis due to intimal hyperplasia. Intimal hyperplasia is thought to result from interactions between areas of exposed subendothelial collagen in an injured vessel and platelets, resulting in platelet adhesion. Saratin, an inhibitor of the vWF-dependent binding of platelet to collagen interaction, has been shown in vitro to reduce the adhesion of platelets to collagen. In the current study, the authors investigated the effects of topical saratin administration in a canine dialysis access model in regard to intimal hyperplasia development at the venous anastomosis. Fourteen female mongrel dogs underwent placement of a femoral polytetrafluoroethylene (PTFE) dialysis access graft and were placed into 1 of 2 groups: 1) control or 2) experimental with topical saratin application. The experimental group had 600 microg of saratin (1 microg/microL) applied for 5 minutes directly onto the venous anastomosis before restoration of blood flow;control groups received vehicle control. At 4 weeks postoperative, a portion of the graft was removed along with a segment of the outflow vein. Veins were subsequently processed, sectioned, and analyzed along the length of the excised segment and divided into blocks that included the area of the graft toe, midanastomotic region and heel, and blocks A-E. Intimal hyperplasia was assessed by a computer-assisted morphometric analysis. Platelet counts and bleeding times were also measured. Vein segments in the control group (n=7) showed pronounced intimal hyperplasia in blocks B, C, and D as compared to the saratin group (n=6). Distribution of intimal hyperplasia by blocks between control and saratin groups were as follows: block [A] 8.6 +/- 1.9 vs 9.7 +/- 3.0% (p=NS), [B] 32.7 +/- 6.3 vs 10.7 +/- 3.5% (p=0.01), [C] 44.8 +/- 6.2% vs 10.3 +/- 1.5% (p=0.0004), [D] 40.8 +/- 11.0 vs 9.1 +/- 4.2% (p=0.02), [E] 7.5 +/- 5.5 vs 2.7 +/- 0.4% (p=NS). Intimal hyperplasia normalized to vein wall thickness also showed a significant reduction with saratin application. Bleeding times and platelet counts obtained at different time points during the experiment showed no difference between control and saratin groups. In a canine dialysis access model using PTFE grafts, topical application of saratin at the venous anastomosis decreased intimal hyperplasia development by as much as 77% when compared with control animals. Saratin provides for a method of substantially reducing intimal hyperplasia by direct local application without systemic side effects.     

Comparison of processed bovine internal mammary arteries and autologous veins as arterial femoral substitutes in dogs: blood compatibility and pathological characteristics

This study was undertaken to compare the chemically processed internal mammary artery (BIMA) and the autologous femoral vein as arterial grafts. The BIMA prosthesis was implanted as a left femoral artery bypass and the femoral vein as a right femoral artery bypass graft in 27 dogs. In groups of three dogs the grafts were implanted for predetermined durations: 4, 24 and 48 hours (short term), 1, 2 and 4 weeks (medium term) and 3, 6 and 9 months (long term). All autologous veins were patent when the dogs were killed. The patency rates of the BIMA grafts were 100% in the short-term group, 67% in the medium-term group and 29% in the long-term group. The deposition of labelled fibrinogen and platelets on flow surfaces, the structural preservation of the wall of the BIMA prosthesis and accumulation of thrombi during the period of implantation were studied.     

Small-caliber heparin-coated ePTFE grafts reduce platelet deposition and neointimal hyperplasia in a baboon model

PURPOSE: Intimal hyperplasia and graft thrombosis are major causes of graft failure. Heparin prolongs graft patency and inhibits neointimal hyperplasia in animal models. The purpose of this study was to evaluate the effect of a heparin-coated expanded polytetrafluoroethylene (ePTFE) graft on platelet deposition and anastomotic neointimal hyperplasia after aortoiliac bypass grafting in a baboon model. METHODS: Heparin-coated ePTFE grafts (4-mm diameter) were incorporated into exteriorized femoral arteriovenous shunts placed in five baboons. Platelet deposition was analyzed by measuring the accumulation of indium 111-labeled platelets on the grafts, with dynamic scintillation camera imaging. Eight adult male baboons (mean weight, 9.3 kg) underwent bilateral aortoiliac bypass grafting with ePTFE grafts (4-mm internal diameter). In each animal a heparin-coated ePTFE graft was placed in one aortoiliac artery, and an uncoated graft, which served as the control, was placed in the contralateral aortoiliac artery. All grafts were harvested at 4 weeks, and were analyzed quantitatively for neointimal hyperplasia at graft-vessel anastomoses. RESULTS: Early platelet deposition on heparin-coated grafts after 1 to 4 hours of ex vivo circuitry was significantly reduced. All the harvested aortoiliac grafts were patent at 4 weeks. There was a significant reduction in neointimal area at both proximal (0.26 +/- 0.11 mm(2)) and distal (0.29 +/- 0.14 mm(2)) anastomoses in the heparin-coated grafts, compared with proximal (0.56 +/- 0.18 mm(2)) and distal (0.63 +/- 0.21 mm(2)) anastomoses in the untreated control grafts (P <.05). In addition, neointimal cell proliferation assayed with bromodeoxyuridine (BrdU) incorporation was reduced in the graft neointima (3.47% +/- 0.43%) in heparin-coated grafts compared with the graft neointima (6.21% +/- 0.59%) in untreated control grafts (P <.05). CONCLUSIONS: Small-caliber heparin-coated ePTFE grafts significantly reduce platelet deposition and anastomotic neointimal hyperplasia and cell proliferation, without measurable side effects, in baboons. Surface coating with heparin in small-caliber ePTFE grafts is useful for improving prosthetic bypass graft patency. Clinical relevance: An autologous vein graft is the ideal bypass conduit in peripheral arterial reconstruction; however, many patients who undergo bypass grafting do not have adequate or available autologous vein graft. As a result surgeons often must rely on prosthetic grafts as an alternative conduit in arterial bypass procedures. Clinical outcomes with prosthetic grafts in peripheral arterial reconstruction are generally inferior to those with autologous vein bypass grafts, in part because of anastomotic neointimal hyperplasia. This study evaluated the effect of small-caliber heparin-coated expandable polytetrafluoroethylene (ePTFE) grafts in aortoiliac reconstruction in a baboon model. The study found that heparin-coated ePTFE grafts resulted in less intimal hyperplasia and less platelet deposition after implantation, compared with noncoated control ePTFE grafts.