Arteriovenous Bypass Grafting Research Articles

Cystathionine Gamma Lyase Is Regulated by Flow and Controls Smooth Muscle Migration in Human Saphenous Vein.

The saphenous vein is the conduit of choice for bypass grafting. Unfortunately, the hemodynamic stress associated with the arterial environment of the bypass vein graft leads to the development of intimal hyperplasia (IH), an excessive cellular growth and collagen deposition that results in restenosis and secondary graft occlusion. Hydrogen sulfide (H2S) is a ubiquitous redox-modifying gasotransmitter that inhibits IH. H2S is produced via the reverse trans-sulfuration pathway by three enzymes: cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). However, the expression and regulation of these enzymes in the human vasculature remains unclear. Here, we investigated the expression of CSE, CBS and 3-MST in segments of native human saphenous vein and large arteries. Furthermore, we evaluated the regulation of these enzymes in vein segments cultured under static, venous (7 mmHg pressure) or arterial (100 mmHg pressure) pressure. CSE was expressed in the media, neointima and intima of the vessels and was negatively regulated by arterial shear stress. Adenoviral-mediated CSE overexpression or RNA interference-mediated CSE knock-down revealed that CSE inhibited primary human VSMC migration but not proliferation. We propose that high shear stress in arteriovenous bypass grafts inhibits CSE expression in both the media and endothelium, which may contribute to increased VSMC migration in the context of IH.

Photochemical Tissue Passivation Reduces Vein Graft Intimal Hyperplasia in a Swine Model of Arteriovenous Bypass Grafting.

BackgroundBypass grafting remains the standard of care for coronary artery disease and severe lower extremity ischemia. Efficacy is limited by poor long‐term venous graft patency secondary to intimal hyperplasia (IH) caused by venous injury upon exposure to arterial pressure. We investigate whether photochemical tissue passivation (PTP) treatment of vein grafts modulates smooth muscle cell (SMC) proliferation and migration, and inhibits development of IH.Methods and Results PTP was performed at increasing fluences up to 120 J/cm2 on porcine veins. Tensiometry performed to assess vessel elasticity/stiffness showed increased stiffness with increasing fluence until plateauing at 90 J/cm2 (median, interquartile range [IQR]). At 90 J/cm2, PTP‐treated vessels had a 10‐fold greater Young's modulus than untreated controls (954 [IQR, 2217] vs 99 kPa [IQR, 63]; P=0.03). Each pig received a PTP‐treated and untreated carotid artery venous interposition graft. At 4‐weeks, intimal/medial areas were assessed. PTP reduced the degree of IH by 66% and medial hypertrophy by 49%. Intimal area was 3.91 (IQR, 1.2) and 1.3 mm2 (IQR, 0.97; P≤0.001) in untreated and PTP‐treated grafts, respectively. Medial area was 9.2 (IQR, 3.2) and 4.7 mm2 (IQR, 2.0; P≤0.001) in untreated and PTP‐treated grafts, respectively. Immunohistochemistry was performed to assess alpha‐smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA). Objectively, there were less SMA‐positive cells within the intima/media of PTP‐treated vessels than controls. There was an increase in PCNA‐positive cells within control vein grafts (18% [IQR, 5.3]) versus PTP‐treated vein grafts (5% [IQR, 0.9]; P=0.02).ConclusionsBy strengthening vein grafts, PTP decreases SMC proliferation and migration, thereby reducing IH.

Hemolytic Anemia with Fragmented Red Blood Cells Following Vascular Access Grafting for Hemodialysis in a Patient with Chronic Kidney Disease

A 57-year-old male who had been treated with hemodialysis due to end-stage chronic kidney disease for 3 years received arterio-venous bypass grafting with a polyurethane vascular access graft in his left upper arm. Two months later, he was diagnosed with hemolytic anemia with fragmented red blood cells (RBC). He had never shown clinical symptoms such as fever or neurological abnormalities characteristic of thrombotic thrombocytopenic purpura (TTP). Moreover, neither thrombocytopenia nor coagulation abnormality was found on routine laboratory examination. He received arterial banding to reduce the blood flow entering the artificial vascular access graft, which led to rapid recovery from hemolytic anemia, without recurrence. This was an extremely rare case of angiopathic hemolytic anemia with fragmented RBC caused by unfavorable bypass grafting, successfully treated with simple reoperation to reduce the blood flow entering the vascular access graft.

Biological vascular grafts for hemodialysis access

Evaluation of: Tillman BW, Yazdani SK, Neff LP et al. Bioengineered vascular access maintains structural integrity in response to arteriovenous flow and repeated needle puncture. J. Vasc. Surg. 56(3), 783–793 (2012).Alternatives to autogenous arteriovenous hemodialysis (HD) access, such as synthetic arteriovenous bypass grafts and central venous catheters, are associated with a higher rate of complications. The evaluated article assessed the repeated cannulation challenges of HD in tissue-engineered blood vessels implanted in a bovine in vivo model (n = 15). Two groups were studied. A short-term group in which the graft was explanted and histologically examined (n = 7) and a second group in which the graft was left in for 6 months or until outflow venous stenosis occurred (n = 8). Two grafts from each group occluded 1-month postoperatively. Of the 11 remaining, cannulation was well tolerated with adequate hemostasis. Histological analysis demonstrated host cell repopulation of the outer surface in the short-term group (n = 5) and stable wall geometry in the long-term group. The authors concluded that their study proves the concept of using a scaffold-based approach to tissue-engineered blood vessels for HD access.

Inhibitory effect of polydioxanone suture external stent on the vein graft neointima thickening and the possible mechanism

Objective To evaluate the effect of a biodegradable external stent on intimal vein graft thickening in an arteriovenous bypass grafting model, and study its possible mechanism. Methods Twenty-four rabbits underwent carotid interposition bypass via ipsilateral jugular vein. Half received the polydioxanone stent ( PDS group) and half a simple vein graft (controls). Group subsets received external stent removal or sham-control exploration at 4th and 12th week. Each of the specimens was detected for pathological and molecular biological examination. Results At 4th and 12th week the PDS group had significantly less medial and intimal thickening than the control group ( P ＜ 0, 05 ), and there were fewer proliferating smooth muscle cells and extra cellular matrix formation than the control group at every interval. The proliferating cell nuclear antigen (PCNA) and angiotensin Ⅱ type 1 receptor (AT1R) were over-expressed in the tunica media and intima in control group. The transforming growth factor-β1 (TGF-β1) was expressed mostly in adventitia in PDS group. Conclusion An macro-porous nonrestrictive, PDS external stent can effectively inhibit the intimal hyperplasia in vein bypass grafts, which might be contributed to the re-distribution of TGF-β1 and AT1R. Key words: Vein graft; Intimal thickening; TGF-β1 ; AT1R

Prosthetic axillary-axillary arteriovenous straight access (necklace graft) for difficult hemodialysis patients: A prospective single-center experience

It is not uncommon for all usual upper limb autogenous access sites to fail, often in patients for whom neither peritoneal dialysis nor transplantation is an appropriate option. Axillary-axillary arteriovenous bypass grafts could be used as the last option before a thigh autogenous access even in case of unilateral central venous stenosis or obstruction. We describe our experience with this procedure in a series of patients. A consecutive series of 18 patients for whom all possible arm accesses had failed and neither peritoneal dialysis nor transplantation was possible underwent a necklace graft formation over a 2.5-year period. All grafts implanted were 6 mm, internally reinforced prostheses made of expanded polytetrafluoroethylene (PTFE, Gore-Tex Intering Vascular Graft, W. L. Gore and Associates, Inc, Flagstaff, Ariz) anastomosed end to side the axillary artery and contralateral vein, and tunneled straight in the subcutaneous space before the sternum. All patients had bimonthly clinical examinations in which the thrill, bruit, skin, cannulation sites, and dialysis adequacy were reviewed. They also had at the same time a transonic assessment where graft flows and recirculation rates were measured. In case of low flow (<600 mL/min) or drop of 20% between two measurements or recirculation >5% a fistulogram was obtained, and an intervention was performed to restore patency. We operated on 10 males and 8 females; mean age was 55.1 years. The primary patency was 83% and 72.2%, and the secondary patency was 94.4% and 88.9% at 6 months and 1 year, respectively. Five successful surgical revisions were carried out for four clotted grafts and one post dialysis rupture. One surgical revision for thrombosis failed and one local infection lead to thrombosis and was not amenable to surgical revision. Three patients died of causes unrelated to their vascular access during the study period. The reasonable patency and minimal complications associated with these bypasses show that they are a valid option for complex patients. We advocate the use of this bypass in patients with exhaustion of all access possibilities in both arms with a patent superior vena cava, subclavian, and brachiocephalic veins. We also indicate it in case of unilateral central venous stenosis or obstruction with complete exhaustion of all other access possibilities on the contralateral side.

Is Basilic Vein Transposition a Real Alternative to an Arteriovenous Bypass Graft? A Prospective Study

Basilic vein transpositions (BVTs) are considered to be superior to arteriovenous bypass grafts (AVGs). However, for the most part studies comparing BVTs to AVGs have been retrospective in design and without a set follow-up protocol. In this analysis, data were prospectively collected from patients with either a BVT or a brachio-axillary AVG. When all other native options were exhausted a BVT was performed if the vein had a diameter of 3 mm. All patients had bimonthly measurements of access inflow and recirculation using ultrasound dilution and were followed up for 2 years. Of 76 patients, 34 had a BVT and 42 an AVG (p > 0.05). BVT group: 12 were male, 22 female, the mean age was 62 and 26% were diabetic. AVG group: 22 were male, 20 female, the mean age was 57 and 56% were diabetic. The maturation delay was higher in the BVT group (6 weeks vs. 2 weeks). For the BVT and AVG groups, at 6, 12 and 24 months, respectively, primary patency was 90% vs. 76% (p < 0.05), 73% vs. 61% and 69% vs. 54% (p > 0.05). Assisted primary patency was 100% vs. 90% (p = 0.1201), 96% vs. 56% and 74% vs. 40% (p < 0.001). Secondary patency was 100% vs. 83%, 93% vs. 70% (p < 0.025) and 85% vs. 62% (p < 0.01). In the BVT group, 18 patients had 32 interventions for a total cost of $127,800, while in the AVG group, 27 patients had 54 interventions for a total cost of $227,300. This is the first prospective study to confirm that BVTs were cost effective and associated with better outcomes when compared with AVGs.

Subnormalization of Left Ventricular Shape after Succesful Coronary Revascularization

It is asumed that the shape and size of the left ventricle could change after successful revascularization and that the shape and size reflect left ventricular function. Echocardiography and Simpson's rule were used for evaluating the endocardial surface area of the left ventricle and elongation of the left ventricle as shape index in 13 patients before coronary arterio-venous bypass grafting (CABG) and 1 year after successful CABG. After successful CABG, the left ventricle becomes bigger and less elongated than before CABG. Results show a change from concentric hypertrophy of the left ventricle before CABG to subnormalization after CABG. We suppose that the subnormalization of left ventricular size and shape is the result of successful CABG and successful rehabilitation. The change of left ventricular size and shape after CABG might depend more on the original state of the left ventricle before surgery.

An endothelin type A receptor antagonist inhibits neointimal hyperplasia and increases luminal area in porcine vein grafts

Abstract Background Neointimal hyperplasia is responsible for the majority of cases of vein graft failure. To date, no pharmacological intervention has proved successful in preventing this process in humans. Endothelin (ET) 1 is a potent vasoconstrictor and promotes the proliferation of vascular smooth muscle cells in vitro. The authors have shown previously that porcine vein grafts contain high levels of ET-1 and ET type A (ETA) receptor subtypes. The aim was to investigate the effect of an ETA receptor antagonist, BSF 302146, on luminal area and graft wall dimensions in a porcine model of arteriovenous bypass grafting. Methods Bilateral saphenous vein–carotid artery interposition grafting was performed in two groups of Large White pigs (26–32 kg; n = 5 per group). BSF 302146 (10 mg kg−1 day−1) was administered orally to animals in group 1; group 2 animals acted as controls. After 4 weeks the grafts were explanted and pressure-fixed ex vivo. Histological sections were obtained and graft dimensions assessed by means of computer-aided planimetry. Results BSF 302146 significantly reduced both neointimal hyperplasia and medial thickening, and increased luminal area by 77 per cent. Conclusion The ETA receptor antagonist BSF 302146 inhibits neointimal hyperplasia and increases luminal area in a porcine model of saphenous vein bypass grafting.

Prevention of venous graft sclerosis with clopidogrel and aspirin combined with a mesh tubing in a dog model of arteriovenous bypass grafting.

to investigate the effect of clopidogrel combined with aspirin or aspirin alone on fibromyointimal hyperplasia (FIMH) in a bypass model with native vein grafts (NVG) and biocompound grafts (BCG). twelve Beagle dogs were randomised into two equal groups. In each animal NVG and a BCG were interposed in the common carotid arteries. Postoperatively, Group 1 received clopidogrel (200 mg/d) and aspirin (100 mg/d) and Group 2 received aspirin (100 mg/d) alone. the BCG was constructed by sheathing the ipsilateral jugular vein with highly flexible metal mesh tubing. After 30 days the grafts were harvested and pressure fixed. FIMH was determined by morphometry. the average wall thickness of the BCG was significantly lower than that of the NVG in both groups (0.26 (SD)0.02 mm vs 0.47 (SD)0.15 mm, p = 0.04 and 0.28 (SD)0.05 mm vs 0.70 (SD)0.29 mm, p = 0.01, respectively). For BCG treated with aspirin, the wall cross section area was lower (5.0 (SD)0.6 mm(2)vs 9.1 (SD)3.3 mm(2), p = 0.02) and the lumen larger (25.2 (SD)5.9 mm(2)vs 9.7 (SD)3.4 mm(2), p < 0.01) than for the NVG. There was also a difference in the lumen cross section area of the NVG, which was larger after combined therapy with clopidogrel and aspirin (17.9 (SD)7.8 mm(2)vs 9.7 (SD)3.4 mm(2), p = 0.04). in this dog model the sheathing of vein grafts effectively prevents FIMH following bypass surgery. Clopidogrel is effective in NVG.

External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting.

Bypass of stenotic coronary arteries with autologous saphenous vein is an established treatment for ischemic heart disease. However, its long-term clinical success is limited. Late vein graft failure is the result of medial and intimal thickening consequent upon medial vascular smooth muscle cell migration, proliferation and extracellular matrix deposition, followed later by superimposed atherosclerosis. These changes directly compromise graft blood flow and provoke thrombosis. Vein graft wall thickening may represent an adaptation imposed by arterial hemodynamic factors, and these factors have been shown to promote vascular smooth muscle cell migration and proliferation through activation of key mediators including platelet-derived growth factor (PDGF). Many pharmacological interventions aimed at preventing these long-term changes have proven unsuccessful in clinical evaluation. We recently demonstrated in a pig saphenous vein graft model that application of an external polyester stent to the outside of carotid interposition vein grafts reduced intimal hyperplasia and total wall thickness 1 month after implantation. However, it is not known whether the benefits of the stent are maintained in the longer term or what mechanisms underlie its effect. The present study therefore compared morphological changes and PDGF expression in stented grafts and contralateral unstented grafts in the same pigs, 6 months after graft implantation. Reduced medial thickening, neointima formation, and cell proliferation were sustained in externally stented grafts, and these effects were associated with a significant reduction in PDGF expression.

Influence of external stent size on early medial and neointimal thickening in a pig model of saphenous vein bypass grafting.

Late saphenous vein graft failure results from intimal and medial thickening due to migration and proliferation of vascular smooth muscle cells and superimposed atheroma. These changes may represent an adaptation by the vein to its insertion into the arterial system. Using a porcine model of arteriovenous bypass grafting, we recently demonstrated that supporting the graft with a nonrestrictive external Dacron velour stent significantly reduced intimal hyperplasia and total wall thickness. In the present study, we investigated the influence of different external stent sizes on graft wall dimensions and cell proliferation. Three stent sizes were tested: mildly restrictive, nonrestrictive, and oversized (5, 6, and 8 mm in diameter, respectively). Four weeks after grafting, total wall thickness was decreased 40% by 5-mm stents (P = .02), 66% by 6-mm stents (P = .0004), and 81% by 8-mm stents (P = .02 versus unstented grafts). Neointimal thickness was reduced almost 62% by 6-mm and 72% by 8-mm stents (both P = .01) but not by 5-mm stents. As a result, the encroachment of the intima into the lumen was reduced approximately 70% by 6- or 8-mm stents (P = .02 and P = .01 versus unstented grafts, respectively). Both neointimal and medial cell proliferation were significantly reduced by all three stents compared with unstented grafts. External stenting of saphenous vein bypass grafts reduces early intimal and medial hyperplasia. Oversized stents give equally profound suppression of intimal thickening, obviating the need for precise size matching with the graft and greatly simplifying the surgical procedure.

External stenting reduces early medial and neointimal thickening in a pig model of arteriovenous bypass grafting

The long-term clinical success of coronary artery bypass grafting with autologous saphenous vein is limited by progressive medial and neointimal thickening in the graft and superimposed atherosclerosis. We sought to reduce wall thickening by applying an external stent to experimental grafts in pigs. The diameter of the stent was designed to allow unrestricted initial expansion of the vein in response to arterial pressure and the stent material was highly porous so as to minimize advential disruption. Four weeks after graft implantation, stented grafts had a larger lumen (11.2 ± 6.2 [standard deviation] mm 2 versus 7.6 ± 3.4 mm 2, p < 0.05, n = 9) and an almost fourfold thinner media (0.14 ± 0.08 versus 0.49 ± 0.22, p < 0.001) and neointima (0.10 ± 0.07 versus 0.35 ± 0.24, p < 0.001) than paired unstented grafts in the same animals. Cell proliferation was also greatly reduced by stenting in the neointimal and medial layers. The stenting procedure devised here is readily applicable to clinical coronary bypass grafts. (J T horac C ardiovasc S urg 1996;112:79-84)

Effects of external stenting on wall thickening in arteriovenous bypass grafts

Late occlusion of the saphenous vein graft appears to result in part from wall thickening as an adaptation to increased mean wall stress. Using an established pig model of arteriovenous bypass grafting, the effect of reducing wall stress with an external porous polytetrafluoroethylene stent was investigated. Segments of autologous saphenous vein were implanted by end-to-end anastomoses into both carotid arteries, with one graft supported by a stent 4 mm in diameter. Increases in graft wall dimensions were quantified 4 weeks later by computer-aided planimetry of transverse histological sections. The contribution of hyperplasia (i.e., cell proliferation) to the changes observed was further clarified by measurements of DNA concentration. All grafts showed an increase in external size, but this was restricted by stenting. All grafts also showed an increase in crosssectional area of the tunica media and tunica intima that was only partly accounted for by an increase in DNA concentration, which indicated that both hyperplasia and hypertrophy had occurred. Stented grafts showed less enlargement of the media but greater enlargement of the intima. Overall wall size was therefore similar in stented and unstented grafts. Stented grafts showed less increase in DNA concentration than unstented grafts. In stented grafts, the residual luminal cross-sectional area was significantly less than in unstented grafts. The data show that external stenting reduces medial enlargement and hyperplasia but increases encroachment of the intima into the lumen. Because final luminal size is thought to be of paramount importance in maintaining long-term patency, external stenting is unlikely to be of benefit.

Subcutaneous heparin and myointimal proliferation in arteriovenous bypass grafts

Subcutaneous heparin and myointimal proliferation in arteriovenous bypass grafts

Distention promotes platelet and leukocyte adhesion and reduces short-term patency in pig arteriovenous bypass grafts

A pig model of autologous saphenous vein to common carotid artery bypass grafting was developed. An end-to-end anastomotic technique led to lower middle graft and distal turbulence. Saphenous veins were surgically prepared with or without distention at 600 mm Hg, implanted into the arterial circulation, and removed 2 hours later. Medial integrity was then assessed by adenosine triphosphate/adenosine diphosphate concentration ratio, and endothelial integrity, leukocyte and platelet adhesion by scanning electron microscopy. In grafts made with undistended vein adenosine triphosphate/adenosine diphosphate concentration ratio was not significantly lower (3.0 +/- 0.1, n = 32) than in freshly isolated vein (3.3 +/- 0.1, n = 26), endothelial cover was 98% +/- 1%, n = 6, and there was little platelet or leukocyte adhesion. In distended grafts adenosine triphosphate/adenosine diphosphate concentration ratio was reduced to 2.2 +/- 0.2 (n = 7, p less than 0.005), endothelial cover was reduced to 38% +/- 14% (n = 6, p less than 0.001), and there was extensive platelet and leukocyte adhesion to exposed subendothelium. In separate experiments graft patency measured at 1 to 5 weeks was significantly greater (96%, n = 25) when undistended vein was used than when distended vein was used (64%, n = 25, p less than 0.005). The data show that distention leads to medial and endothelial damage and that this is associated with increased platelet and leukocyte adhesion and with reduced early patency.

Intimal changes in arteriovenous bypass grafts: Effects of varying the angle of implantation at the proximal anastomosis and of producing stenosis in the distal runoff artery

Autologous arteriovenous bypass grafts were constructed between external iliac arteries in 20 mongrel dogs to determine the development of intimal fibromuscular hyperplasia. Animals received grafts at 55, 90 or 120 degree angles relative to the proximal anastomosis. Five animals with 90 degree angle grafts were also subjected to 80% stenosis in the runoff artery. All grafts showed the development of a fibromuscular tunica intima. Qualitative or quantitative intimal differences were not observed among grafts placed at 90 degree angles, 90 degree angles with runoff artery stenosis, or 120 degree angles. Grafts placed at 55 degree angles relative to the proximal anastomosis developed a consistently thicker fibromuscular layer in the tunica intima when compared to the other groups. These changes which were segmental in nature, occurred in the proximal and distal grafts and over the distal anastomosis.