A nitinol "U-Clip" versus sutured arteriovenous anastomosis: local tissue response and intimal hyperplasia development in a sheep model.

OBJECTIVES: This study sought to compare the local tissue response and subsequent volume of intimal hyperplasia (IH) that develops throughout the maturation of an arteriovenous fistula created using continuous/interrupted polypropylene with that of a novel, metal-alloy, penetrating anastomotic clip device. MATERIALS AND METHODS: Forty-six fistulae were created in 23 sheep under a paired design using the nitinol U-Clip (n = 23) in one hind limb and continuous (n = 20) or interrupted (n = 3) polypropylene suture for the other. Animals were killed at 4 (n = 3), 14 (n = 3), 28 (n = 10), 42 (n = 3), and 180 (n = 4) days. Histological sections were evaluated for quantitative histology and immunohistochemistry. RESULTS: Compared with continuous polypropylene, U-Clip specimens demonstrated less intima-media area per unit length (IMA/L), proliferating cells, and tissue necrosis at all time points (MANOVA, F = 9.8-24.1, all p ≤ .005; observed power >82%). Specifically, values of IMA/L were reduced by 5% (p = .97), 37% (p = .02), 33% (p < .01), 9% (p = .42), and 14% (p = .22) at the time points of 4, 14, 28, 42, and 180 days respectively. Proliferating cells were reduced by 75% (p < .01), 72% (p = .03), 76% (p = .03), 27% (p = .31), and 60% (p = .01) and tissue necrosis by 67% (p < .01), 58% (p = .02), 40% (p = .33), 21% (p = .43), 77% (p = .11). In a 28-day comparison between U-Clip and interrupted polypropylene the U-Clip group demonstrated a 4% (p = .65) reduction in IMA/L, 74% (p < .01) in proliferating cells and 49% (p < .05) in tissue necrosis. CONCLUSIONS: These results provide evidence of reduced local tissue necrosis, proliferating cells, and IH, favouring arteriovenous fistulae created using the U-Clip anastomotic device over conventional polypropylene suture techniques most evident over the first 4 weeks.

Current and evolving strategies for the treatment of atherosclerotic disease of the popliteal artery.

The popliteal artery (PA) may well be the most challenging of all infra-inguinal vessels to treat. Not only is it anatomically unique but it's also exposed to some of the most brutal forces seen in the lower limb, during normal knee flexion. Management may be challenging and with few randomized trials dedicated to answering questions of technical success and durability the correct approach remains contentious. Herein we seek to describe and evaluate the growing number of options for treatment in this vascular territory.

Drug eluting stents in the treatment of below the knee arterial occlusive disease.

The use of endovascular techniques for the treatment of occlusive arterial disease below the knee has gained widespread acceptance and is considered by many as the first line treatment for patients with critical limb ischaemia. Tibial angioplasty and stenting have a high rate of technical success and are relatively low risk procedures, which has widened their applicability to include treatment for the elderly and those with comorbidities unsuitable for open bypass surgery. Despite these advantages the durability of the percutaneous revascularisation remains inferior to that of open surgery for diffusely diseased arteries. In the search to improve their long term performance we have sought to investigate the role of coronary drug eluting stents (DES) in the tibial vasculature in the hope that they may reduce recurrent stenosis, the leading threat to interventional patency. Ample data now exists in the form of registries and randomised trials designed to evaluate the use of DES in the crural arteries below the knee. This article reviews this body of research, explores the use of these devices in more complex lesions, speculates on their future development and examines their cost-effectiveness.

Re-entry device use in the endovascular treatment of aorto-iliac occlusive disease.

The treatment of peripheral arterial occlusive disease with endovascular therapy is rapidly becoming the standard of care. Akin to the movement towards percutaneous coronary interventions that occurred with gusto throughout the 1980s and 1990 s, treatment for the peripheral vasculature has undergone its own paradigm shift. Such that many feel that a first-line catheter-based approach is justified for the majority of patients in 2012. Extensive occlusive disease of the aorto-iliac segment is an area where open surgery has historically been preferred over endovascular therapy. This is partly because the open surgical standard of aorto-bi-femoral bypass has durability unrivalled by other forms of peripheral revascularisation surgery. Furthermore, some have avoided endovascular interventions in this region because of fears of perforation, bleeding and limited technical success in an area where the blood vessels carry a heavy burden of disease and a large thrombotic load. Throughout surgical history we have seen advances in technology emerge to provide a medium through which the proceduralist may extend their indications for treatment. A number of re-entry devices which provide a reliable method of wire passage beyond chronic occlusions of the aorta and iliac arteries have emerged and for the first time are safely facilitating high technical success rates in the treatment of aorto-iliac occlusive disease (AIOD). What follows is a summary of both open and endovascular treatment options for AIOD. Moreover, this review will provide an evidence based description of the emerging litany of devices which aid in wire passage through this most challenging of vascular territories.

An arteriovenous fistula model of intimal hyperplasia for evaluation of a nitinol U-Clip anastomosis.

OBJECTIVES: The aim of this study was to create an ovine arteriovenous fistula (AVF) model which would closely replicate a human forearm fistula and use this to quantify the degree of intimal hyperplasia in those created with the U-Clip compared to a conventional sutured anastomosis. MATERIALS AND METHODS: Twenty AVFs were created in 10 Border Leicester-Merino sheep between the superficial femoral artery and vein of each hind limb. On one side the U-Clip and on the other a continuous polypropylene suture was used to perform the anastomosis. The animals were sacrificed at 2 (n = 3), 4 (n = 4), 6 (n = 3) weeks and histological slices were taken of each AVF in cross section to determine the intimal media area per unit length (IMA/L). RESULTS: Intimal hyperplasia (IH) was observed at all time points with one AVF found occluded with thrombus at the time of harvest. The IMA/L was significantly lower in the U-Clip groups by 24% at 2 weeks, 32% at 4 weeks and 23% at 6 weeks (Two-way ANOVA, p = 0.019, observed power = 0.825, time or side p ≥ 0.766, type p = 0.001; Paired t-test, p < 0.001 between matched anastomotic types). Time taken to perform the anastomosis was similar between the two anastomotic techniques (Polypropylene 14(8-18) vs. U-Clip 15.3(11-23) min; p = 0.47). CONCLUSION: This ovine AVF model results in IH similar to that seen in a human AVF. The IH that occurs with the U-Clip is less than that of continuous polypropylene suture.

Arm vein as a last autogenous option for infrainguinal bypass surgery: it is worth the effort.

OBJECTIVES: Considerable evidence exists for the use of arm vein conduit in lower limb bypass surgery. The use of arm vein in preference to synthetic conduit as a last autogenous option was assessed for patency and limb salvage outcomes. MATERIALS AND METHODS: A prospective database was interrogated and checked against TQEH operating theatre database to detect all infrainguinal arm vein bypasses performed between 1997 and 2005. Patency, limb salvage and survival data for 37 arm vein bypasses was calculated using the Kaplan-Meier survival estimate method. RESULTS: There were no perioperative deaths. 30 day patency rates were 89% primary, 95% secondary and 95% limb salvage. 12 month patency rates were 56% primary, 79% secondary and 91% limb salvage. 5 year patency rates were 37% primary, 76% secondary and 91% limb salvage. There was no significant patency advantage for primary vs. "redo" grafts (p=0.54), single vessel vs. spliced conduits (p=0.33) or popliteal vs tibial outflow (p=0.80). Patient survival rate was 92% and 65% at 1 and 5 years respectively. CONCLUSION: Lower limb bypasses using arm vein can be performed with favourable patency and limb salvage compared to synthetic conduits. However, secondary interventions are frequently required to maintain patency. We recommend a vigilant surveillance program for early identification of patency threatening disease.

The role of the fibrocyte in intimal hyperplasia.

BACKGROUND: Experimental animal studies have shown that the intimal hyperplasia (IH) responsible for occlusion after successful revascularization procedures may be partially caused by a bone marrow-derived cell that migrates to the site of vascular injury. Concurrent studies have demonstrated an extensive role in wound healing for the circulating fibrocyte. OBJECTIVES: We aimed to trace the path of the circulating cell that contributes to IH and determine if it is the fibrocyte. METHODS AND RESULTS: We established an in vitro model whereby purified monocytes from six healthy human volunteers were cultured into fibrocytes. These cells were morphometrically similar to the vascular smooth muscle cell (VSMC) found in IH and expressed alpha-smooth muscle actin (alpha-SMA) as well as CD34, CD45 and Collagen I (Col I), markers indicative of the fibrocyte. In an in vivo ovine carotid artery synthetic patch graft model, carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeled circulating leukocytes were observed throughout the graft as well as in the neointima in 18 sheep. These cells were shown to produce collagen and alpha-SMA at 1, 2 and 4 weeks. These cells then underwent immunohistochemical analysis and were found to express a set of markers unique to the fibrocyte (CD34, CD45, Vimentin and alpha-SMA) and also to double stain for CD34 and alpha-SMA. CONCLUSIONS: IH in an ovine carotid artery patch graft model is partially derived from a hematopoietic circulating progenitor cell that acquires mesenchymal features as it matures at the site of injury.