Anastomotic Intimal Hyperplasia Research Articles

Lower Extremity Bypass for Occlusive Disease: A Brief History

ObjectivesThis is a narrative review that aims to highlight key advancements which led to the current state of lower extremity bypass surgery. It focuses on key contributors during the last century who have driven the standardization of surgical treatment of peripheral arterial occlusive disease. MethodsA narrative review was conducted utilizing available resources in the scientific and historical literature to track landmark achievements in the development of modern lower extremity bypass surgery for occlusive disease, focusing primarily on the last century of advancement. ResultsSeveral critical conceptual, technological, and technical landmarks were identified as critical components of modern lower extremity bypass surgery. This includes fundamental development in the techniques of vascular anastomosis led by Carrel and others, a developing understanding of vascular occlusive disease as a localized and segmental process with broad implementation of the techniques of arteriography, and the development of safe thromboendarterectomy aided by the development and utilization of heparin for anti-coagulation. These factors led to the first femoral to popliteal artery bypass by Jean Kunlin in 1948. From here, advances in vascular prosthetic material pioneered by Voorhees and others, alternative vascular conduits, increasing acceptance of tibial revascularization, and dispelling the myth of diabetic “small vessel” disease broadened revascularization options for patients with complex patterns of occlusive disease and those who have limited conduit availability. ConclusionsModern lower extremity bypass surgery for occlusive disease arose steadily over the course of a century driven by complex problem-solving in the pathophysiological understanding of atherosclerosis, technical developments in vascular anastomosis and arteriography, and evolution in conduit materials and pharmacologic therapy. Future advancements in bypass surgery are targeted on solving the complex problems of anastomotic intimal hyperplasia, expanding technology for alternative vascular conduits, ongoing optimization of risk factors and scrutiny of outcomes to make patient-centered, evidence-based decisions regarding revascularization strategy.

Advancing tissue-engineered vascular grafts via their endothelialization and mechanical conditioning.

Tissue engineering has garnered significant attention for its potential to address the predominant modes of failure of small diameter vascular prostheses, namely mid-graft thrombosis and anastomotic intimal hyperplasia. In this review, we described two main features underpinning the promise of tissue-engineered vascular grafts: the incorporation of an antithrombogenic endothelium, and the generation of a structurally and biomechanically mimetic extracellular matrix. From the early attempts at the in-vitro endothelialization of vascular prostheses in the 1970s through to the ongoing clinical trials of fully tissue-engineered vascular grafts, the historical advancements and unresolved challenges that characterize the current state-of-the-art are summarized in a manner that establishes a guide for the development of an effective vascular prosthesis for small diameter arterial reconstruction. The importance of endothelial cell purity and their arterial specification for the prevention of both diffuse neointimal hyperplasia and the accelerated development of atherosclerotic lesions is delineated. Additionally, the need for an extracellular matrix that recapitulates both the composition and structure of native elastic arteries to facilitate the protracted stability and patency of an engineered vasoactive conduit is described. Finally, the capacity of alternative sources of cells and mechanical conditioning to overcome these technical barriers to the clinical translation of an effective small diameter vascular prosthesis is discussed. In conclusion, this review provides an overview of the historical development of tissue-engineered vascular grafts, highlighting specific areas warranting further research, and commentating on the outlook of a clinically feasible and therapeutically efficacious vascular prosthesis for small diameter arterial reconstruction.

Development of Poly(1,8-octanediol-co-citrate-co-ascorbate) Elastomers with Enhanced Ascorbate Performance for Use as a Graft Coating to Prevent Neointimal Hyperplasia.

Small-diameter expanded polytetrafluoroethylene (ePTFE) graft surfaces have poor long-term patency due to limited endothelial cell (EC) coverage and anastomotic intimal hyperplasia. Multifunctional elastomers that coat the ePTFE graft surface to promote EC adhesion while simultaneously inhibiting intimal hyperplasia are highly desirable. Poly(diol-co-citrate) (PDC), a thermoset elastomer, is biodegradable, biocompatible, and mimics vascular mechanical properties. Engineering antioxidant components into PDC polymeric structures improves biocompatibility by attenuating oxidative stress yet is limited by bioavailability. Herein, we develop a new ascorbate protection and deprotection strategy (APDS) for loading bioactive ascorbic acid into the structure of PDC elastomers to improve poly(1,8-octanediol-co-citrate-co-ascorbate) (POCA) prepolymer ascorbate activity. Elastomers cured from APDS POCA prepolymers provide twice the active ascorbate sites on the elastomer surface (35.19 ± 1.64 ng mg-1 cm-2) versus unprotected POCA (Un.POCA, 18.31 ± 0.97 ng mg-1 cm-2). APDS POCA elastomers displayed suitable mechanical properties for vascular graft coating [Young's modulus (2.15-2.61 MPa), elongation (189.5-214.6%) and ultimate tensile strength (2.73-3.61 MPa)], and superior surface antioxidant performance through 1,1-diphenyl-2-picrylhydrazyl free radical scavenging and lipid peroxidation inhibition as compared to poly(1,8-octanediol-co-citrate) (POC) and Un.POCA. Hydrolytic degradation of APDS POCA occurred within 12 weeks under physiological conditions with a mass loss of 25.8 ± 3.4% and the degradation product retaining ascorbate activity. APDS POCA elastomer surfaces supported human aortic endothelial cell proliferation while inhibiting human aortic smooth muscle cell proliferation in vitro. APDS POCA elastomer surfaces displayed superior decomposition of S-nitrosothiols compared to POC and Un.POCA. Taken together, these findings indicate the potential of APDS POCA elastomers to serve as bioactive, therapeutic coatings that enhance the long-term patency of small diameter ePTFE grafts.

Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of Heparin-Bonded Polytetrafluoroethylene Propaten Graft in a Chronic Canine Femoral Artery Bypass Model

Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long-term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology in a canine model. Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control nonheparin graft was placed on the contralateral side. The graft patency was assessed at 1, 6, 12, 18, and 24months (n=5 per group) following the bypass. Heparin bioactivity of the graft material was analyzed. The effect of intimal hyperplasia was also assessed. All bypass grafts were patent at 1 month. Significantly greater patency rates were noted in the Propaten group compared to the control group at 12, 18, and 24months, which were 84%, 80%, and 80% vs. 55%, 35%, and 20%, respectively (P<0.02). There was a significant reduction in the anastomotic neointimal area and neointimal cell proliferation in Propaten grafts compared with control grafts at all groups between 6 and 24months (P<0.05). Heparin bioactivity as measured by antithrombin binding assay was demonstrated in the Propaten graft between 1 and 24months. Mean heparin activities on Propaten grafts ranged from 26.3±6.4 pmol/cm2 to 18.4±8.7 pmol/cm2 between 1 and 24months, which were significantly greater than the control group (P<0.001). Differences between mean heparin activities of explanted Propaten graft samples at the various time points were nonsignificant (P>0.05). Heparin-bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten graft confers an advantage in long-term graft patency.

TCTAP C-081 After Recent Coronary Artery Bypass Grafting and Left Internal Mammary Artery Serious Anastomotic Intimal Hyperplasia, Native Left Anterior Descending Branch Was Deal with Drug Eluting Balloon by the Support of Intra-aortic Balloon Pump

### Patient initials or identifier number Hou FX ### Relevant clinical history and physical exam The patient complained of chest pain with exertion one year before, thenwas admitted to Qinghai province hospital, and one drug-eluting stent wasdeployed in LAD after CAG. Half a year later, the stent

Evaluation of a novel vascular graft with a distal bifurcation designed to reduce the development of intimal hyperplasia. Experimental study in a porcine aorta model

Abnormal haemodynamics is commonly agreed to be a major contributor to the development of distal anastomotic intimal hyperplasia. A new vascular graft design proposed by computational studies was used to demonstrate its surgical feasibility and to compare it with the conventional graft in a porcine model. The device was used in 12 eight-month-old pigs, six received the new graft and six had a conventional graft. The proximal graft end was implanted into the aorta, the distal graft end was implanted into the iliac artery. The host artery was ligated in order to simulate occlusion. At 20 weeks after surgery the pigs were killed and the device was excised for histological and morphometric analysis. In five experimental grafts the reconstruction was occluded due to thrombosis; only one prosthesis was patent showing a minimum of neointimal hyperplasia. In the control group too only three of the six grafts were patent. A histological analysis revealed, as the cause of occlusion, fibrous tissue overgrowth corresponding in structure to neointimal hyperplasia. Differences in the number of obliterations and in occlusion rates between the profiles of the two groups were evaluated using the median test (P<0.05). The results were not statistically significant. Although mathematical modelling had shown significant haemodynamic benefits of a naturally bifurcated graft, our study did not confirm its superiority over conventionally used prostheses.

SiRNA Transfection With Cholesterol Modification From Electrospun PET Facilitates Gene Silencing in Human Aortic Smooth Muscle Cells

Anastomotic intimal hyperplasia (AIH) remains the leading cause for prosthetic arterial graft failure. RNAi is a promising tool to silence genes such as Thrombospondin-2 (TSP-2), previously shown by our group to be upregulated in AIH. The present study is aimed at delivering modified TSP-2 siRNA (3’cholesterol tagged TSP-2 siRNA) from electrospun polyethylene terephthalate (ePET) and therefore knocking down TSP-2 gene and ultimately inhibiting AIH.

Numerical analysis of coronary artery bypass grafts: An over view

Arterial bypass grafts tend to fail after some years due to the development of intimal thickening (restenosis). Non-uniform hemodynamics following a bypass operation contributes to restenosis and bypass failure can occur due to the focal development of anastomotic intimal hyperplasia. Additionally, surgical injury aggravated by compliance mismatch between the graft and artery has been suggested as an initiating factor for progress of wall thickening along the suture line Vascular grafts that are small in diameter tend to occlude rapidly. Computational fluid dynamics (CFD) methods have been effectively used to simulate the physical and geometrical parameters characterizing the hemodynamics of various arteries and bypass configurations. The effects of such changes on the pressure and flow characteristics as well as the wall shear stress during a cardiac cycle can be simulated. Recently, utilization of fluid and structure interactions have been used to determine fluid flow parameters and structure forces including stress and strains relationships under steady and transient conditions. In parallel to this, experimental diagnostics techniques such as Laser Doppler Anemometry, Particle Image Velocimetry, Doppler Guide wire and Magnetic Resonance Imaging have been used to provide essential information and to validate the numerical results. Moreover, clinical imaging techniques such as magnetic resonance or computed tomography have assisted considerably in gaining a detailed patient-specific picture of the blood flow and structure dynamics. This paper gives a review of recent numerical investigations of various configurations of coronary artery bypass grafts (CABG). In addition, the paper ends with a summary of the findings and the future directions.

Supplemental oxygen controls smooth muscle cell proliferation and anastomotic intimal hyperplasia at in arteriovenous fistulas in rabbits

BackgroundThe number of patients with end-stage renal disease (ESRD) continues to rise in the world. About 39% prevalent haemodialysis patients underwent creation of arteriovenous fistulas (AVF) as the primary vascular...

Thrombospondin-2 Gene Silencing in Human Aortic Smooth Muscle Cells Improves Cell Attachment

Despite decades of research, anastomotic intimal hyperplasia remains a major cause of delayed prosthetic arterial graft failure. Previously, we reported profound upregulation of thrombospondin-2 (TSP-2) mRNA in neointimal smooth muscle cells after prosthetic arterial bypass graft placement. TSP-2 is an antiangiogenic matricellular protein with specific functions yet unknown. In this study, we hypothesized that inhibition of TSP-2 in human aortic smooth muscle cells (HAoSMCs) would reduce cell proliferation and migration in vitro, providing a therapeutic target to mitigate intimal hyperplasia. HAoSMCs were transfected with TSP-2 small interfering ribonucleic acid (siRNA) using a commercial transfection reagent. Gene silencing was evaluated using semiquantitative real-time polymerase chain reaction. ELISA was used to measure TSP-2 protein levels in cell culture supernatants. Cell migration and proliferation were assessed using scratch wound assays and alamar blue assays, respectively. Attachment assays were performed to assess the effect of TSP-2 silencing on HAoSMC adhesion to fibronectin. TSP-2 siRNA achieved consistent target gene silencing at 48 hours post-transfection in HAoSMCs. This single transfection allowed suppression of TSP-2 protein expression for more than 30 days. TSP-2 gene silencing did not affect HAoSMC migration or proliferation. MMP-2 levels were also unaffected by changes in TSP-2 protein levels. However, HAoSMC attachment to fibronectin improved significantly in cells treated with TSP-2 siRNA. siRNA-mediated TSP-2 silencing of human aortic HAoSMCs improved cell attachment but had no effect on cell migration or proliferation. The effect on cell attachment was unrelated to changes in MMP activity.

Distal Anastomotic Intimal Hyperplasia: Histocytomorphology, Pathophysiology, Etiology, and Prevention.

The ubiquitous relationship of late graft occlusion, particularly the nonautogenous bypasses and distal anastomotic intimal hyperplasia (DAIH), has been extensively investigated. After having established the specific location of DAIH in human autogenous, biologic and prosthetic late graft occlusion, canine models were designed to elucidate the role of compliance mismatch between graft and the host artery and the configuration of the distal end to side versus end to end anastomosis using autogenous artery. DAIH occurred in all end to side anastomosis but not in side matching end to end anastomosis. Compliance mismatched is not the cause of DAIH development, but it enhances the pathogenesis. Further study using pharmacologic agents to modulate the activities of vascular myoblasts was successful in attenuating DAIH development and progression. Since DAIH occurs through a cascade of events initiated by endothelial lifting of the overlapping processes at the gap junction to allow blood borne elements to enter the subendothelial space, then incites myoblast proliferation and matrix synthesis leading to DAIH formation at the heel and toe where oscillatory flow exists. Control of myoblast activity is needed on a permanent basis to prevent DAIH development and progression. Cessation of treatment allows resurgence of DAIH biogenesis. Direct regulation of vascular myoblast activity preclude the need of inhibiting other source of stimuli that increases as our knowledge of the subject grows. Without the participation of myoblast, there will be no DAIH irrespective of the potency and numbers of enzymatic, hormonal, or mechanical inciting factors. DAIH is a byproduct of oscillatory flow at the heel and the toe which enable blood borne elements to enter subendothelial space via the gap junction subsequent to lifting of endothelial cell overlapping processes. Pharmacologic control aiming at inactivating the myoblast in proliferation and matrix synthesis is a logical mode to control DAIH formation and late graft failure. Our experimental models confirm the success in controlling DAIH using heparin fraction that lack the anticoagulant yet is active in antiproliferative effect on myoblasts.

Comparison of Two Different Arteriovenous Anastomotic Forms By Numerical 3D Simulation of Blood Flow.

Anastomotic intimal hyperplasia caused by unphysiological hemodynamics is generally accepted as a reason for dialysis access graft occlusion. Optimizing the venous anastomosis can improve the patency rate of arteriovenous grafts. The purpose of this study was to examine, evaluate and characterize the local hemodynamics, and in particular, wall shear stresses in conventional venous end-to-side anastomosis and in patch form anastomosis (Venaflotrade mark) by Computational Fluid Dynamics (CFD). The flow simulations were carried out as three-dimensional to extend results of our previous 2D studies. The numerical simulation was done with a finite volume-based algorithm. The anastomotic forms were constructed with usual size and fixed walls. Subdividing the flow domain into multiple control volumes solved the fundamental equations. The boundary conditions were constant for both forms. The velocity profile of the patch form is better than for the conventional form. The region of high static pressure caused on flow stagnation is reduced on the vein floor. The anastomotic wall shear stress is decreased. The results of this study strongly support patch form use to reduce the incidence of intimal hyperplasia and venous anastomotic stenoses.

Is a Vein Patch Worthwhile for Femoropopliteal Bypass With ePTFE Grafts?

One of the factors contributing to late graft occlusion after peripheral arterial bypass with prosthetic grafts is anastomotic intimal hyperplasia. The purpose of this study was to evaluate, experimentally and clinically, the effect of placing a vein patch over the site of distal anastomosis of a ePTFE graft in peripheral arterial bypass (DAPP). After heparinization, the infrarenal abdominal aorta in 14 beagle dogs was resected, and an ePTFE graft was interposed between the resected ends. The dogs were divided into a control group without DAPP and a DAPP group. These animals were killed 3 months after surgery. A total of 89 femoropopliteal bypasses using ePTFE grafts, 71 patients were divided into two groups for analysis; namely, a direct suture group without DAPP being the DS group (n = 62 limbs) and a DAPP group with DAPP (n = 27 limbs). The mean follow-up period was 1010 days in the DS group and 302 days in the DAPP group. All the grafts were patent in both groups of dogs. The thrombus adhering to the entire intraluminal surface of the graft defined as the mean thrombus-covering ratio, in the DAPP group was significantly less than that in the control group, although there were no significant differences in the length of proximal or distal intimal ingrowth into the ePTFE grafts between the two groups. The maximal intimal thickness did not differ significantly between the control group and the DAPP group, at 541 +/- 349 µm and 353 +/- 76 µm, respectively. The 1- and 3-year cumulative patency rates of femoropopliteal bypasses were 86% and 71%, respectively, in the DS group, whereas they were both 91% in the DAPP group. Although the numbers of subjects in this study was too limited for a final evaluation, the trend was unmistakable. The findings of this study indicate that DAPP may improve the cumulative patency of femoropopliteal bypasses with ePTFE grafts.http://link.springer-ny.com/link/service/journals/00547/bibs/8n4p193.html</hea

Local Hemodynamics and Intimal Hyperplasia at the Venous Side of a Porcine Arteriovenous Shunt

Venous anastomotic intimal hyperplasia (IH) observed in the arteriovenous shunt (AVS) has been associated with disturbed hemodynamics. This study aims to correlate hemodynamics with wall histology and wall mechanics by examining the flow field in AVS with computational fluid dynamics using experimental data taken from in vivo experiments. Input data to the computational model were obtained in vivo one month after AVS creation; adjacent vessels were submitted to histological and mechanical examination. The 3-D shunt geometry was determined using biplane angiography. Ultrasound measurements of flow rates were performed with perivascular flow probes and pressures were recorded through intravascular catheters. These data were considered as boundary conditions for calculation of the unsteady flow field. Numerical findings are suggestive of strong Dean vortices toward both vein flow exits, verified by color Doppler. The high wall shear stresses (WSSs) and their gradients appear to be related to areas of IH and vessel wall stiffening, as evidenced in preliminary histological and mechanical studies of the venous wall. Additionally, suture line hyperplasia seems to be aggravated by the high WSS gradients noted at the transition line from graft to vein.

Antioxidant therapy reverses impaired graft healing in hypercholesterolemic rabbits

Limited endothelial cell (EC) coverage and anastomotic intimal hyperplasia contribute to thrombosis and failure of prosthetic grafts. Lipid accumulation and lipid oxidation are associated with decreased EC migration and intimal hyperplasia. The goal of this study was to assess the ability of antioxidants to improve graft healing in hypercholesterolemic animals. Rabbits were placed in one of four groups: chow plus N-acetylcysteine (NAC), chow plus probucol, chow with 1% cholesterol plus NAC, or chow with 1% cholesterol plus probucol. After 2 weeks, expanded polytetrafluoroethylene grafts (12 cm long x 4-mm internal diameter) were implanted in the abdominal aorta. Grafts were removed after 6 weeks and analyzed for cholesterol content, EC coverage, anastomotic intimal thickness, and the cellular composition of the neointima. Plasma samples were obtained to assess systemic oxidative stress. The data were compared with previously reported data from animals fed diets of chow and chow with 1% cholesterol. Prosthetic grafts from rabbits fed chow with 1% cholesterol had significantly greater anastomotic intimal thickening and lower EC coverage than grafts from rabbits fed a regular chow diet. In hypercholesterolemic rabbits, antioxidant therapy decreased global oxidative stress as evidenced by a 40% decrease in plasma thiobarbituric acid reactive substances. In rabbits fed the chow with 1% cholesterol diet, NAC decreased intimal hyperplasia at the proximal anastomosis by 29% and significantly increased graft EC coverage from 46% to 71% (P = .03). Following a similar pattern, probucol decreased intimal hyperplasia by 43% and increased graft EC coverage to 53% in hypercholesterolemic rabbits. Global oxidative stress and anastomotic intimal hyperplasia are increased, and endothelialization of prosthetic grafts is significantly reduced in rabbits fed a high-cholesterol diet. Antioxidant treatment improves EC coverage and decreases intimal hyperplasia. Reducing oxidative stress may promote healing of prosthetic grafts.

Sustained local drug delivery from a novel polymeric ring to inhibit intimal hyperplasia

The long-term clinical success of autologous vein and synthetic vascular grafts are limited because of the development of anastomotic intimal hyperplasia (IH). We have previously published data suggesting that cyclosporine (CyA) may reduce the development of IH in a canine model (Hirko et al., J Vasc Surg 1993;17:877-887). However, systemic administration of CyA could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of CyA from a polymeric vascular wrap would prevent the development of IH. To test this hypothesis, we developed a controlled release polymeric ring that could be placed around anastomotic sites to deliver therapeutic drugs locally. The ring is a composite polymeric device consisting of poly(DL-lactide-co-glycolide) (PLGA) microspheres embedded in a poly(ethylene glycol) hydrogel. Several in vitro studies were conducted to evaluate the effects of different sterilization procedures on the properties of the device. It was determined that gamma sterilization was the preferred sterilization method of choice for this device. In vivo studies were conducted on a swine model to evaluate the biocompatibility of the ring. The histological findings of the ring implants at 2 and 4 weeks demonstrate the biocompatibility of this device.

Effects of Batroxobin on distal anastomotic intimal hyperplasia after expanded polytetrafluoroethylene bypass grafting in dog common carotid artery

To study the morphological behavior, the expression of MCP-1 and PDGF-B of distal anastomotic neointima after expanded polytetrafluoroethylene (ePTFE) bypass grafting. And to identify the effects of Batroxobin (BX) on distal anastomotic intimal hyperplasia. 12 adult mongrel dogs underwent end to side bypass grafting in left common carotid artery using ePTFE vascular graft (6mm in diameter, 5cm in length) were divided randomly into two groups. All 12 bypass grafts were removed 28 days after grafting and distal anastomotic parts were obtained. Using HE, Masson, IHC, RT-PCR and western blot, we analyzed the thickness, relative content of ECM, SMC PCNA index, expression of MCP-1 and PDGF-B in distal anastomotic neointima. And we compared the differences between the two groups. 28 day after grafting, the neointima was formed by SMC and ECM and was covered by epithelial cells. After using BX, the thickness of neointima was reduced [( 381.3 +/- 144.7) microm versus (213.8 +/- 29.0) microm, P < 0.05] and the relative content of ECM were significantly decreased (P = 0.006). The PCNA index (P = 0.109) and PDGF-B level (P = 0.055 by RT-PCR and P = 0.337 by WB) between the two groups had no significant difference. MCP-1 level was markedly decreased (P = 0.025 by RT-PCR and P = 0.016 by WB). Using BX after ePTFE grafting could effectively reduce the relative content of ECM, reduce the expression of MCP-1 and decrease the thickness of neointima in the early time.

Blood vessel replacement: 50 years of development and tissue engineering paradigms in vascular surgery

The gold standard material in bypass surgery of blood vessels remains the patient's own artery or vein. However, this material may be unavailable, or may suffer vein graft disease. Currently available vascular prostheses, namely polyethylene terephthalate (PET, Dacron) and expanded polytetrafluoroethylene (ePTFE), perform well as large-caliber replacements, but their long-term patency is discouraging in small-caliber applications (<6 mm), such as in coronary, crural or microvessel surgery. This failure is mainly a result of an unfavorable healing process with surface thrombogenicity, due to lack of endothelial cells and anastomotic intimal hyperplasia caused by hemodynamic disturbances. An ideal small-diameter vascular graft has become a major focus of research. Novel biomaterials have been manufactured, and tissue-biomaterial interactions have been optimized. Tissue engineering technology has proven that the concept of partially or totally living blood vessels is feasible. The purpose of this review is to outline the vascular graft materials that are currently being implanted, taking into account cell-biomaterial physiology, tissue engineering approaches and the collective achievements of the authors.

Technical Notes and Tips: Non-Ligation of the Distal Cephalic Vein Maintains Patency of Median Cubital Vein Arteriovenous Fistulae

The utilisation of the median cubital vein is a recognised technique for upper arm arteriovenous fistula formation. In our experience, when the median cubital vein is suitable for arteriovenous fistula formation, the distal cephalic vein should not be ligated and divided. By preserving the continuity of the cephalic vein, venous drainage from the forearm will maintain patency of the cephalic vein in the arm in the event of median cubital vein occlusion secondary to anastomotic intimal hyperplasia. Furthermore, if the fistula is ligated following transplantation, cephalic vein drainage is preserved allowing the future formation of a brachiocephalic fistula. Figure 1 (A) Pre-operative anatomy. (B) Postoperative anatomy, cephalic vein left in continuity. (C) Postoperative anatomy, cephalic vein ligated.

Inhibition of anastomotic intimal hyperplasia using a chimeric decoy strategy against NF B and E2F in a rabbit model

Neointimal formation remains a major limitation after arterial reconstruction. To overcome this problem, we focused on two important transcription factors, nuclear factor-kappaB (NFkappaB) and E2F. The purpose of this study was to determine the effects of simultaneous inhibition of these transcription factors on the formation of neointimal hyperplasia. We employed chimeric decoy oligodeoxynucleotides (ODN) to inhibit both NFkappaB and E2F simultaneously, and examined the effects of chimeric decoy ODN on the proliferation and migration of cultured vascular cells and on the formation of neointimal hyperplasia using prosthetic graft placement in a rabbit hypercholesterolemia model. Our in vitro study demonstrated that transfection of chimeric decoy ODN inhibited platelet-derived growth factor (PDGF)-induced proliferation and migration of vascular smooth muscle cells, whereas endothelial cell proliferation was not inhibited. In an in vivo study, treatment with chimeric decoy ODN significantly inhibited proximal and distal anastomotic intimal hyperplasia, and accelerated re-endothelialization. alpha-Smooth muscle actin (alpha-SMA)-positive cell proliferation was inhibited at the anastomotic sites. Expression of PDGF-BB and PDGF receptor-beta was also suppressed by chimeric decoy ODN, resulting in a reduction of alpha-SMA-positive cell accumulation. In addition, chimeric decoy ODN treatment inhibited macrophage accumulation, which was accompanied by a reduction of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 gene expression. The present study demonstrates the feasibility of chimeric decoy ODN treatment for preventing neointimal formation. This strategy might be useful to improve the clinical outcome after arterial reconstruction.