Effects of posture on shear rates in human brachial and superficial femoral arteries

Shear rate is significantly lower in the superficial femoral compared with the brachial artery in the supine posture. The relative shear rates in these arteries of subjects in the upright posture (seated and/or standing) are unknown. The purpose of this investigation was to test the hypothesis that upright posture (seated and/or standing) would produce greater shear rates in the superficial femoral compared with the brachial artery. To test this hypothesis, Doppler ultrasound was used to measure mean blood velocity (MBV) and diameter in the brachial and superficial femoral arteries of 21 healthy subjects after being in the supine, seated, and standing postures for 10 min. MBV was significantly higher in the brachial compared with the superficial femoral artery during upright postures. Superficial femoral artery diameter was significantly larger than brachial artery diameter. However, posture had no significant effect on either brachial or superficial femoral artery diameter. The calculated shear rate was significantly greater in the brachial (73 +/- 5, 91 +/- 11, and 97 +/- 13 s(-1)) compared with the superficial femoral (53 +/- 4, 39 +/- 77, and 44 +/- 5 s(-1)) artery in the supine, seated, and standing postures, respectively. Contrary to our hypothesis, our current findings indicate that mean shear rate is lower in the superficial femoral compared with the brachial artery in the supine, seated, and standing postures. These findings of lower shear rates in the superficial femoral artery may be one mechanism for the higher propensity for atherosclerosis in the arteries of the leg than of the arm.     

Murine Model of Femoral Artery Wire Injury with Implantation of a Perivascular Drug Delivery Patch

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. While these therapies lead to the rapid restoration of blood flow, these technologies remain limited by restenosis in the case of bare metal stents and angioplasty, or reduced healing and possibly enhanced risk of thrombosis in the case of drug eluting stents. A key pathophysiological mechanism in the formation of restenosis is intimal hyperplasia caused by the activation of vascular smooth muscle cells and inflammation due to arterial stretch and injury. Surgeries that induce arterial injury in genetically modified mice are useful for the mechanistic study of the vascular response to injury but are often technically challenging to perform in mouse models due to the their small size and lack of appropriate sized devices. We describe two approaches for a surgical technique that induces endothelial denudation and arterial stretch in the femoral artery of mice to produce robust neointimal hyperplasia. The first approach creates an arteriotomy in the muscular branch of the femoral artery to obtain vascular access. Following wire injury this arterial branch is ligated to close the arteriotomy. A second approach creates an arteriotomy in the main femoral artery that is later closed through localized cautery. This method allows for vascular access through a larger vessel and, consequently, provides a less technically demanding procedure that can be used in smaller mice. Following either method of arterial injury, a degradable drug delivery patch can be placed over or around the injured artery to deliver therapeutic agents.     

The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423]

Background

Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery. The process of saphenous vein intimal hyperplasia begins just days after surgical revascularization, setting the stage for graft atherosclerotic disease and its sequalae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following coronary artery bypass surgery.

Methods

Patients undergoing multi-vessel coronary artery bypass grafting and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for a one year duration starting on the day of surgery (as soon as postoperative bleeding has been excluded). At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The trial will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery.

Discussion

This trial is the first prospective human study that will address the question of whether clopidogrel therapy improves outcomes and reduces saphenous vein graft intimal hyperplasia following cardiac surgery. Should the combination of clopidogrel and aspirin reduce the process of vein graft intimal hyperplasia, the results of this study will help redefine modern antiplatelet management of coronary artery bypass patients.     

MCP-1 deficiency is associated with reduced intimal hyperplasia after arterial injury

Monocyte chemoattractant protein (MCP)-1 is abundant in smooth muscle cells (SMC) and macrophages of atherosclerotic plaques and in the injured arterial wall. MCP-1 and its receptor, CCR2, are important mediators of macrophage accumulation and atherosclerotic plaque progression. We have recently reported that CCR2(-/-) mice have a approximately 60% decrease in intimal hyperplasia and medial DNA synthesis in response to femoral arterial injury. We have now examined the response to femoral arterial injury in MCP-1(-/-) mice. MCP-1 deficiency was associated with a approximately 30% reduction in intimal hyperplasia at 4 weeks and was not associated with diminished medial DNA synthesis. Despite inducing tissue factor in SMC culture, MCP-1 deficiency was not associated with a decrease in neointimal tissue factor after injury. These data suggest that MCP-1 and CCR2 deficiencies have distinct effects on arterial injury. The effects of MCP-1 on intimal hyperplasia may be mediated largely through SMC migration.     

Prevention of late lumen loss after coronary angioplasty by photodynamic therapy: Role of activated neutrophils

Restenosis after coronary angioplasty arises from fibrocellular intimal hyperplasia and possibly failure of the artery to enlarge adequately. Which mechanisms underlie this process is only partly understood. No drugs have been clinically effective in reducing the incidence of restenosis. Since recently, photodynamic therapy (PDT) is being investigated as a possible treatment for intimal hyperplasia. PDT involves the systemic administration of a light-excitable photosensitizer that is takers up rather preferentially by rapidly proliferating cells. During laser irradiation light energy is transferred from the photosensitizer to oxygen generating the highly reactive singlet oxygen. This potent oxidizer can cause severe cellular damage. After PDT of a balloon-injured artery from the rat and rabbit the media remained acellular for several weeks to months, and intimal hyperplasia did not occur. The endothelial lining regenerated by two weeks, but why smooth muscle cells did not repopulated the media is not known.Neutrophils seem to play an important role in the prevention of restenosis after coronary angioplasty, since the activation status of this type of phagocyte is directly related to vessel diameter at late follow-up. Furthermore, it has been observed that neutrophils adhere to the microvascular wall upon PDT in vivo. In vitro findings suggest that the increased neutrophil adherence was not dependent on a decreased release of the anti-adhesive factors NO and prostacyclin by the PDT-treated endothelial cells. Furthermore, PDT did not stimulate the expression of P-selectin by the endothelial cells, one of the adhesion receptors for neutrophils. The endothelial cells only retract upon PDT allowing the adherence of neutrophils by their ₂-integrin adhesion receptors to the subendothelial matrix. On the basis of these findings, we presume that the successful prevention of intimal hyperplasia by PDT partly depends on the presence of the neutrophil at the site of the lesion.     

辛伐他汀干预鼠颈动脉损伤MCP-1的表达

应用鼠颈动脉结扎模型,采用原位杂交、免疫组化技术观察血管单核细胞趋化蛋白-1(monocyte chemoattractant protein-1, MCP-1)的表达及内膜增生情况,探讨辛伐他汀抗内膜增生机制.结果发现损伤血管内膜增生明显,MCP-1的表达增加;辛伐他汀干预可明显抑制血管MCP-1的表达及新生内膜形成.提示血管内膜增生可能与MCP-1表达上调有关,辛伐他汀抑制内膜增生也许通过MCP-1介导.     

RECK基因在兔颈动脉壁损伤后再狭窄过程中的表达

目的:通过建立动物损伤模型,分析RECK基因在兔子颈动脉球囊损伤术后的表达与动脉内膜变化和官腔狭窄的相关性。方法:兔子手术损伤侧的动脉血管设置为实验组,未进行手术操作的一侧动脉作为对照组。建立动脉模型的四个时间点7、14、21、28 d,在麻醉状态下处死模型动物。取得所需长度的损伤动脉血管及对照组动脉血管。将取得的标本进行HE病理染色,通过计算机图像计算软件观察标本动脉内膜随时间的变化;同时通过western-blot方法测定RECK蛋白表达水平、real-time PCR测量RECK基因表达量。结果:血管手术损伤后,血管内膜面积在随着术后日期的增长呈逐渐增厚变化,血管内膜与中层比值逐渐增大,同对照实验组比较,有统计学意义(P0.05)。实验组及对照组的中膜无显著增生。结论:RECK基因在组织中表达变化影响MMPs基因表达。实验论证了在动脉损伤后RECK基因参与了血管再狭窄,为血管再狭窄研究寻得新的研究方向。     

Rotational in vitro compliance measurement of diverse anastomotic configurations: a tool for anastomotic engineering

Anastomotic configurations with a small internal diameter are prone to intimal hyperplasia which can cause occlusion within weeks or months. A link between intimal hyperplasia and inhomogenities of the elastic profile of the anastomosis has been established, making anastomotic engineering directed towards smoothing the compliance profile at the anastomotic site essential. Methods to date restrict the anastomotic compliance measurement to one plane. We present a method by which the anastomotic configurations are rotated, thereby allowing an anastomotic elastic profile assessment in multiple planes. Eight end-to-end anastomoses (ovine common carotid artery) and three end-to-side anastomoses (e-PTFE graft to ovine common carotid artery) were prepared and mounted in an artificial circulation system. Anastomotic circumferential compliance (maximal-minimal diameter/(maximal-minimal pressure.minimal diameter)) was measured by means of a laser-scan-micrometer and a Statham pressure transducer. By rotating end-to-end anastomoses, the compliance was measured in three, and in end-to-side anastomoses in four different planes. Multiplanar compliance variability in areas remote to both end-to-end and end-to-side anastomoses was approximately 9%. At the suture line the variability was approximately 22% in end-to-end anastomoses and 78% in end-to-side anastomoses. These results show that local factors result in different compliance profiles when utilizing a multiplanar technique, particularly in end-to-side anastomoses. The rotational apparatus is a tool which can be used to more accurately engineer a homogeneously compliant anastomosis, with the ultimate goal of prolonging anastomotic patency.     

Involvement of altered arginase activity, arginase I expression and NO production in accelerated intimal hyperplasia following cigarette smoke extract

In the present experiments, we tried to elucidate whether changes in arginase activity, protein expression of arginase-I and -II, and NO production are involved in accelerating the intimal hyperplasia following administration of cigarette smoke extract (CSE). The intimal hyperplasia was caused by removing endothelial cells with the aid of balloon embolectomy catheter in the right carotid artery of the male rabbit. The left carotid artery underwent sham operation and served as control. CSE was prepared by bubbling a stream of cigarette smoke into phosphate buffered saline. Rabbits were given subcutaneously with CSE once a day for 5 weeks from 1 week before to 4 weeks after the surgery. The specimens were assessed histologically and the intima/media ratio (%) was evaluated as an index of the intimal hyperplasia. The accelerated intimal hyperplasia with CSE was accompanied by the augmentation of the impaired cyclic GMP production, enhanced overall arginase activity and up-regulation of arginase-I. Pearson's correlation coefficient analyses revealed the close relationships among the arginase activities in endothelial cells and smooth muscle layer, the intimal/media ratio and cyclic GMP production. These results suggest that the enhanced arginase activity together with facilitated up-regulation of arginase-I with CSE, which was associated with the augmented impairment of NO production, shed a new light on the processes associated with accelerating the intimal hyperplasia in rabbit carotid arteries following CSE.     

Lack of intimal hyperplasia response in an experimental model of non-endothelial vascular wall damage.

The endothelial and medial layers are generally presumed to play an important role in the appearance and development of intimal hyperplasia. We have carried out a short-, media- and long-term study of the morphological changes taking place in the common iliac artery of rats after surgical removal of the adventitial layer. Our aim has been to assess the likely role played by this layer in the development of intimal hyperplasia. Our results show recurrent periods of cellular desquamation and almost complete absence of hyperplastic response during the first two months. After three months three is a slow process of endothelialization which is completed by the 6th month and persists one year after adventitial resection. Thus, adventitial resection seems to cause instability at the subendothelial bed level, not allowing the junction and embedding of endothelial cells nor the development of intimal hyperplasia. This lack of hyperplasia might also result from the fact that the endothelial desquamation process does not involve cellular rupture, which would prevent mitogenic-factor release. After morphological repair of the endothelium, a slow morphofunctional recovery of the artery takes place.     

Biomechanical, morphological and zero-stress state characterization of jugular vein remodeling in arteriovenous fistulas for hemodialysis

While the role of hemodynamic variables on the development of intimal hyperplasia in arteriovenous fistulas for hemodialysis has been examined, less is known about the intramural biomechanical factors. In this study, arteriovenous fistulas were created by implantation of e-PTFE grafts between carotid artery and jugular vein in healthy pigs. In vivo recordings exhibited a three-fold pressure and flow elevation in grafted veins after fistula creation, remaining so until sacrifice. The chief morphological observation in grafted vessels was wall thickening at two weeks, serving to restore intramural stresses to homeostatic levels, and a less marked internal diameter enlargement, gradually normalizing intimal shear after four weeks. The residual strains and opening angle, specifying the zero-stress configuration, increased with differences reaching significance at twelve weeks. Association with histomorphological findings on intima, media and adventitia growth disclosed a correlation between intimal hyperplasia and opening angle increase. Elastin and cellular contents diminished opposite to collagen content, most differences occurring within the first four weeks after grafting. Inflation/extension testing showed that post-fistula the vein wall became progressively thicker and stiffer, lacking restoration of compliance to baseline levels. The present data may further our understanding of the dynamics of venous biomechanical remodeling under pressure and flow-overload conditions.     

Hydroxyapatite electret accelerates reendothelialization and attenuates intimal hyperplasia occurring after endothelial removal of the rabbit carotid artery

The present experiments were designed to investigate whether electrically polarized hydroxyapatite (HA electret) modifies reendothelialization and intimal hyperplasia occurring after endothelial removal of the rabbit carotid artery. Both HA electret and non-polarized HA, which served as a control, had been powdered and mixed with agarose gel. One of the two was applied around the external surface of the carotid artery. Histological analyses revealed that HA electret but not control HA significantly inhibited intimal hyperplasia. The number of Ki67-positive cells detectable in the intimal layer was significantly fewer in the HA electret group. In the HA electret group, abundant TUNEL-positive cells were detected in the media. The number of CD31-positive cells detected on the luminal surface was significantly higher in the HA electret group. Endothelium- and nitric oxide (NO)-dependent relaxation in response to carbachol was significantly improved only in the HA electret group. In conclusion, this is the first report demonstrating that HA electret significantly improved intimal hyperplasia by accelerating the regeneration of functioning endothelial cells and enhancing the apoptosis of medial smooth muscle cells.     

Human-derived nanoparticles and vascular response to injury in rabbit carotid arteries: proof of principle

Self-calcifying, self-replicating nanoparticles have been isolated from calcified human tissues. However, it is unclear if these nanoparticles participate in disease processes. Therefore, this study was designed to preliminarily test the hypothesis that human-derived nanoparticles are causal to arterial disease processes. One carotid artery of 3 kg male rabbits was denuded of endothelium; the contralateral artery remained unoperated as a control. Each rabbit was injected intravenously with either saline, calcified, or decalcified nanoparticles cultured from calcified human arteries or kidney stones. After 35 days, both injured and control arteries were removed for histological examination. Injured arteries from rabbits injected with saline showed minimal, eccentric intimal hyperplasia. Injured arteries from rabbits injected with calcified kidney stone- and arterial-derived nanoparticles occluded, sometimes with canalization. The calcified kidney stone-derived nanoparticles caused calcifications within the occlusion. Responses to injury in rabbits injected with decalcified kidney stone-derived nanoparticles were similar to those observed in saline-injected animals. However, decalcified arterial-derived nanoparticles produced intimal hyperplasia that varied from moderate to occlusion with canalization and calcification. This study offers the first evidence that there may be a causal relationship between human-derived nanoparticles and response to injury including calcification in arteries with damaged endothelium.     

Sex hormones and aortic wall remodeling in an arteriovenous fistula

Background: An arteriovenous fistula (AVF) creates high blood flow through the artery and fistula. With this high flow, there is flow-induced remodeling and an increase in diameter, but no intimal hyperplasia. Estrogen has been shown to modify vascular remodeling, decreasing intimal hyperplasia after endothelial injury.Objective: These experiments tested the hypothesis that estrogen administration would decrease wall thickness in an AVE model. Because estrogen may decrease wall thickness, we also tested the hypothesis that testosterone would increase wall thickness.Methods: A fistula was created between the abdominal aorta and the inferior vena cava in Sprague-Dawley rats to generate high blood flow conditions in the aorta. Four groups of female animals were examined: sham, control with AVE ovariectomized (OVX) with AVE and OVX plus testosterone with AVE Four groups of male animals were also examined: sham, control with AVE castrated with AVE and castrated plus estrogen with AVE Five weeks after creation of the AVF, the aortas were collected and fixed; wall thickness was measured both proximal and distal to the AVEResults: Ovariectomy resulted in a significant decrease in estrogen levels (P < 0.01). Testosterone administration tended to increase testosterone levels in the OVX females, but values did not approach levels observed in the control males. No difference was noted in the proximal wall thickness between the control and the OVX animals. The OVX females receiving testosterone exhibited a significant increase in both proximal and distal wall thickness compared with control females (P < 0.001). In the male animals, there was no significant change in aortic wall thickness in the castrated rats compared with the controls. Estrogen administration in the castrated males resulted in a significant decrease in wall thickness in the proximal and distal aorta (P < 0.05).Conclusion: These studies suggest that, in a model of vascular remodeling, estrogen administration decreases wall thickness, and testosterone administration increases wall thickness.     

Simulation of Flow through a Miller Cuff Bypass Graft

Unnatural temporal and spatial distributions of wall shear stress in the anastomosis of distal bypass grafts have been identified as possible factors in the development of anastomotic intimal hyperplasia in these grafts. Distal bypass graft anastomoses with an autologus vein cuff (a Miller cuff) interposed between the graft and artery have been shown to alleviate the effects of intimal hyperplasia. In this study, pulsatile flow through models of a standard end-to-side anastomosis and a Miller cuff anastomosis are computed and the resulting wall shear stress and pressure distributions analysed. The results are inconclusive, and could be taken to suggest that the unnatural distributions of shear stress that do occur along the anastomosis floor may not be particularly important in the development of intimal hyperplasia. However, it seems more likely that the positive effects of the biological and material properties of the vein cuff, which are not considered in this study, somehow outweigh the negative effects of the shear stress distributions predicted to occur on the floor of the Miller-cuff graft.     

Measurement in vitro of pulsatile arterial diameter using a helium-neon laser

A noncontacting in vitro measurement of pulsatile arterial diameter using a scanning optical micrometer is described. The major component of this system is a He-Ne laser whose beam scans the pulsating artery to be measured. The laser micrometer was integrated into a pulsatile perfusion apparatus that imposed various hemodynamic conditions on excised canine vessels. The laser system reliably tracked the pulsating arterial diameter at a particular longitudinal site as well as at various increments in the presence of an experimentally created stenosis. The He-Ne laser measured the radial motion of canine arteries and various vascular substitutes anastomosed in an end-to-end fashion. From these novel measurements, calculations were made of arterial compliance and bending stress, two biomechanical parameters that are implicated as potential causes of anastomotic intimal hyperplasia and graft failure. Although this device is inherently limited to in vitro use, it is a potentially useful instrument for vascular physiology and biophysics.     

Do P2X purinergic receptors regulate skeletal muscle blood flow during exercise?

Although there is evidence that sympathetic nerves release ATP as a neurotransmitter to produce vasoconstriction via P2X purinergic receptors, the role of these receptors in the regulation of blood flow to exercising skeletal muscle has yet to be determined. We hypothesized that there is tonic P2X receptor-mediated vasoconstriction in exercising skeletal muscle. To test this hypothesis, the effect of P2X receptor blockade on skeletal muscle blood flow was examined in six exercising mongrel dogs. P2X receptor antagonism was accomplished with pyridoxal-phosphate-6-azophenyl-2'4'-disulfonic acid (PPADs). Animals were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. PPADs (40 mg) was infused as a bolus into the femoral artery catheter during steady-state exercise at 6 miles/h. Intra-arterial infusion of PPADs increased iliac blood flow from 542 +/- 55 to 677 +/- 69 ml/min (P < 0.05) and iliac vascular conductance from 5.17 +/- 0.62 to 6.53 +/- 0.80 ml.min(-1).mmHg(-1). The PPADs infusion did not affect blood flow in the contralateral iliac artery. These data support the hypothesis that P2X purinergic receptors produce vasoconstriction in exercising skeletal muscle.     

A functional model of microvascular thrombosis

A new model of microvascular thrombosis is presented, with the evaluation of single-dose heparin in the prevention of microvascular thrombosis. The technique, which involves arterial crushing and an arteriotomy with intimal abrasion, was performed on the superficial femoral artery of the rat. The model was applied to a series of 30 consecutive rat superficial femoral arteries. A 100 percent thrombosis rate was seen immediately and at 24 hours in 10 nonheparinized animals. An operator control group of 10 vessels without intimal abrasion had a patency rate of 100 percent immediately and at 24 hours. Ten vessels following single-dose heparin and intimal abrasion were all patent initially, with 7 remaining patent at 24 hours. Reproducibility of the model was documented by a second operator with similar results. Utilizing this model, single-dose heparin was effective in maintaining vessel patency.     

Simulation of flow through a Miller cuff bypass graft

Unnatural temporal and spatial distributions of wall shear stress in the anastomosis of distal bypass grafts have been identified as possible factors in the development of anastomotic intimal hyperplasia in these grafts. Distal bypass graft anastomoses with an autologus vein cuff (a Miller cuff) interposed between the graft and artery have been shown to alleviate the effects of intimal hyperplasia. In this study, pulsatile flow through models of a standard end-to-side anastomosis and a Miller cuff anastomosis are computed and the resulting wall shear stress and pressure distributions analysed. The results are inconclusive, and could be taken to suggest that the unnatural distributions of shear stress that do occur along the anastomosis floor may not be particularly important in the development of intimal hyperplasia. However, it seems more likely that the positive effects of the biological and material properties of the vein cuff, which are not considered in this study, somehow outweigh the negative effects of the shear stress distributions predicted to occur on the floor of the Miller-cuff graft.     

Intimal hyperplasia and wall shear in arterial bypass graft distal anastomoses: an in vivo model study

The observation of intimal hyperplasia at bypass graft anastomoses has suggested a potential interaction between local hemodynamics and vascular wall response. Wall shear has been particularly implicated because of its known effects upon the endothelium of normal vessels and, thus, was examined as to its possible role in the development of intimal hyperplasia in arterial bypass graft distal anastomoses. Tapered (4-7 mm I.D.) e-PTFE synthetic grafts 6 cm long were placed as bilateral carotid artery bypasses in six adult, mongrel dogs weighing between 25 and 30 kg with distal anastomotic graft-to-artery diameter ratios (DR) of either 1.0 or 1.5. Immediately following implantation, simultaneous axial velocity measurements were made in the toe and artery floor regions in the plane of the anastomosis at radial increments of 0.35 mm, 0.70 mm, and 1.05 mm using a specially designed 20 MHz triple crystal ultrasonic wall shear rate transducer Mean, peak, and pulse amplitude wall shear rates (WSRs), their absolute values, the spatial and temporal wall shear stress gradients (WSSG), and the oscillatory shear index (OSI) were computed from these velocity measurements. All grafts were harvested after 12 weeks implantation and measurements of the degree of intimal hyperplasia (IH) were made along the toe region and the artery floor of the host artery in 1 mm increments. While some IH occurred along the toe region (8.35+/-23.1 microm) and was significantly different between DR groups (p<0.003), the greatest amount occurred along the artery floor (81.6+/-106.5 microm, mean +/- S.D.) (p < 0.001) although no significant differences were found between DR groups. Linear regressions were performed on the paired IH and mean, peak, and pulse amplitude WSR data as well as the absolute mean, peak, and pulse amplitude WSR data from all grafts. The mean and absolute mean WSRs showed a modest correlation with IH (r = -0.406 and -0.370, respectively) with further improvements seen (r = -0.482 and -0.445, respectively) when using an exponential relationship. The overall best correlation was seen against an exponential function of the OSI (r = 0.600). Although these correlation coefficients were not high, they were found to be statistically significant as evidenced by the large F-statistic obtained. Finally, it was observed that over 75 percent of the IH occurred at or below a mean WSR value of 100 s(-1) while approximately 92 percent of the IH occurred at or below a mean WSR equal to one-half that of the native artery. Therefore, while not being the only factor involved, wall shear (and in particular, oscillators wall shear) appears to provide a stimulus for the development of anastomotic intimal hyperplasia.