Vascular Bypass Grafts Research Articles

A Reproducible Porcine ePTFE Arterial Bypass Model for Neointimal Hyperplasia

Late failure of prosthetic vascular bypass grafting using expanded polytetrafluoroethylene (ePTFE) is secondary to the development of neointimal hyperplasia, most commonly at the distal anastomosis. To develop therapies that can improve upon current prosthetic vascular bypass grafting, a large animal model of prosthetic bypass grafting that results in reproducible neointimal hyperplasia is necessary. We performed bilateral end-to-side carotid artery bypasses with 6 mm ePTFE in a porcine model (n = 11). We studied graft patency using magnetic resonance angiography (MRA, 3 wk), duplex ultrasonography (4 wk), and digital-subtraction contrast angiography (4 wk). Animals were sacrificed at 4 wk and morphometric analysis was performed. Of the 11 animals that underwent surgery, one pig died from respiratory compromise; of the remaining 10, graft patency was 90% at 4 wk. Peak systolic and end diastolic velocities were established for this model using ultrasonography. MRA, ultrasonography, and angiography confirmed graft patency and were complimentary tools to evaluate the grafts. Development of neointimal hyperplasia was reproducible at 4 wk in both the proximal and distal anastomoses (2.5 to 3 mm(2)) of the ePTFE bypass grafts. We developed a reproducible porcine ePTFE carotid artery bypass model for studying neointimal hyperplasia. Not only does this model allow for the manipulation and evaluation of potential therapies, but patency and neointimal hyperplasia can be easily evaluated by traditional means, such as MRA, ultrasonography, and angiography. This preclinical model is ideal for evaluation of novel therapies in vivo designed to inhibit neointimal hyperplasia following arterial reconstruction with prosthetic bypass grafting.

Recanalization of an Occluded Infrainguinal Vein Graft Complicated by Graft Aneurysm

The technique of subintimal angioplasty has been described for the recanalisation of native vessels after occlusion of infrainguinal vascular bypass grafts. We report a case in which an attempt at such treatment resulted in inadvertent but successful recanalisation of the occluded vein graft instead. This was complicated by graft perforation and subsequent graft aneurysm which was successfully treated with a covered stent.

Forefoot Amputation with Limb Revascularization: The Effects of Amputation, Timing, and Wound Closure on the Peripheral Vascular Bypass Graft Site

Much has been written about the effects of successful arterial bypass on forefoot surgery for ulceration and gangrene. This study examined the effects of the amputation site and timing on the arterial bypass graft site. We reviewed the records of all patients who had successful vascular bypass graft surgery and amputation at our institution, between October, 1995 and May, 2002. Thirty-eight procedures in 35 patients fit the criteria and were included in the study. Thirty-five patients had successful vascular bypass graft surgery and forefoot amputation for gangrene or nonhealing ulceration. Three of these patients developed gangrene on the contralateral side and received similar treatment for that side. All of the wounds eventually healed. Healing time, rate of graft infection, and rate of wound dehiscence did not differ noticeably between patients with amputation immediately after arterial bypass and patients with amputation one or more days after arterial bypass. Infection at the bypass site occurred in two patients; their amputation sites were closed primarily. Wound dehiscence developed at the bypass site in one patient whose amputation site was closed by secondary intention. Although not statistically significant, the median healing time in patients treated with primary closure (37 days) was less than that in patients treated with closure by secondary intention (61 days; p = 0.09), and rates of graft infection and wound dehiscence did not differ between these two groups of patients. Amputation site wound closure may adversely affect the bypass graft, but results were not statistically significant. Treatment requires a closely coordinated team approach between the vascular surgeon and the orthopedic surgeon.

Tissue engineering applications to vascular bypass graft development: The use of adipose-derived stem cells

The burgeoning field of vascular tissue engineering holds promise for the creation of a practical and successful small-diameter arterial bypass graft. Many creative combinations of autologous cells and scaffolds exist along with an equally long list of microenvironmental cues used to create a functional arterial conduit. This review outlines our work using abdominal wall fat as a source of autologous stem cells for vascular tissue engineering, focusing specifically on this stem cell's availability and potency to differentiate into endothelial-like cells. In a series of 49 patients undergoing elective peripheral vascular surgery, an abundant quantity of adult stem cells was harvested from fat obtained by liposuction. The efficacy of the isolation did not appear influenced by advanced age, obesity, renal failure, or vascular disease, although fat from diabetic patients yielded significantly less stem cells. In addition, these adipose-derived stem cells acquired several morphologic and molecular endothelial phenotypes when exposed to growth factors (endothelial cell growth supplement and vascular endothelial growth factor) and physiologic shear stress in vitro. Taken together, these studies suggest that fat appears to be a viable source of autologous stem cells for use in vascular tissue engineering.

Photodynamic Therapy Reduces Intimal Hyperplasia in Prosthetic Vascular Bypass Grafts in a Pig Model

Bypass surgery has a failing frequency of 30% during the first year, mainly due to intimal hyperplasia (IH). This negative effect is most pronounced in artificial grafts. Photodynamic therapy (PDT) is a technique in which light activates photosensitizer dyes to produce free-radicals resulting in an eradication of cells in the vascular wall. The aim of this study was to determine the effectiveness of PDT to reduce IH in a preclinical porcine PTFE bypass model. Ten pigs were used. After a pilot PDT dosimetry study (n=3) PTFE grafts were bilaterally placed into the circulation as bypasses from the common to the external iliac arteries (n=7). The right sides served as controls (C). Before implantation of the left grafts, the arterial connecting sites of the left distal anastomoses were PDT-treated. The arteries were pressurized at 180 mmHg for 5 minutes with the photosensitizer Methylene Blue (330 microg/ml), and thereafter endoluminally irradiated with laser light (lambda = 660 nm, 100 mW/cm(2), 150 J/cm(2)). After 4 weeks the specimens were retrieved and formalin fixed. Cross sections through the midportions of the distal anastomoses and the grafts were used for histology, immunohistochemistry to identify inflammatory cells and morphometric evaluation (n=7). No systemic side effects and no graft occlusions were noted. PDT-treated anastomoses showed reduced IH in the mid-portions of the anastomoses (Area of IH: microm(2)/microm graft: C: 6970+/-1536, PDT: 2734+/-2560; P<0.005) as well as in the grafts (C: 5391+/-4031, PDT: 777+/-1331; P<0.02). The number of inflammatory cells per microscopic field was increased after PDT (C: 24+/-16, PDT: 37+/-15; P<0.009). Adjuvant PDT, performed in an endovascular fashion, was a safe method to reduce prosthetic graftstenosis in a preclinical setting. This study underscores the clinical potential of PDT to inhibit the development of clinical bypass graftstenosis.

Evidence suggests rigid aortic grafts increase systolic blood pressure: Results of a preliminary study

Abdominal aortic aneurysm (AAA) is a serious complication of the aorta and is treated using vascular bypass grafts. Two main classes of graft are available to treat AAA; grafts implanted by open surgery and stent-grafts implanted using minimally invasive endovascular techniques. Both classes of graft consist of an aortic section which bifurcates into two iliac sections. It has been hypothesized that implantation of aortic grafts and stent-grafts serve to significantly increase abdominal aortic pressures. In this study, an open-loop computer-controlled pumping system was built to produce physiologically realistic pressure and flow-rates. Models of a compliant abdominal aortic aneurysm, a compliant walled graft and a tapered graft were manufactured using an injection moulding technique and fused deposition modelling was used to create a rigid walled graft. A specific transient flow-rate waveform was then applied at the inlet of each model and the resulting pressure waveforms 30 mm upstream from the bifurcation was recorded. Peak pressure measurements were recorded over the course of the pulse for each model. The compliant aneurysm model was found to have a systolic pressure of 107 mmHg while the complaint graft model was 153 mmHg. The rigid graft model had a peak systolic pressure of 199 mmHg. In the tapered graft, the peak pressure dropped to 142 mmHg. The data suggests that implanting a graft model in place of an aneurysm model in an in vitro flow circuit can increase the pressures recorded upstream from the iliac bifurcation and that tapered grafts may alleviate this problem.

Achieving the ideal properties for vascular bypass grafts using a tissue engineered approach: a review

The multiple demands placed on small calibre cardiovascular bypass grafts have meant that a synthetic prosthesis with good long-term patency has not been developed. A tissue-engineered graft could fulfil the ideal characteristics present in an artery. However, the great disadvantage of such a conduit is the time necessary for maturation leading to unacceptable delays once the decision to intervene surgically has been made. This maturation process is essential to produce a graft which can withstand haemodynamic stress. Once implanted, the tissue-engineered graft can contract in response to immediate haemodynamic conditions and remodel in the long term. We review the latest tissue engineering approaches used to give the favourable properties of mechanical strength, arterial compliance, low thrombogenicity, long-term resistance towards biodegradation as well as technological advances which shorten the time required for production of an implantable graft.

Development of Tissue Engineered Vascular Grafts

Vascular bypass grafting is a commonly performed procedure for ischemic heart disease and peripheral vascular disease. However, approximately one in fourteen patients do not have suitable autologous arteries or veins available for grafting. Synthetic vascular grafts were introduced in the 1960s to overcome these problems, but while they perform adequately in high-flow, large-diameter vessel settings they are generally not suited to low-flow, small-diameter vessels. Tissue engineering is a relatively new discipline that offers the potential to create replacement structures from autologous cells and biodegradable polymer scaffolds. Because tissue engineering constructs contain living cells, they may have the potential to grow, self-repair, and self-remodel. Therefore, recently there has been much interest in the use of this technique to produce low-flow small-diameter arteries. The latest and most exciting developments in this area involve the use of multipotent stem cells as a cell source for tissue engineering of vascular grafts (both in vivo and in vitro).

New vessels: Vascular tissue engineering

The use of vascular bypass grafts in patients is not new. The high prevalence of atherosclerosis has seen them being used in the treatment of some of the 800 000 cases of myocardial infarction in the UK. So, is there a need for tissue-engineered blood vessels if there is a functional prosthetic alternative? While this may hold true for vessels with high-blood-flow rates1, the patency rates of poly(ethylene terephthalate) (Dacron®) and expanded polytetrafluoroethylene (ePTFE) grafts are less satisfactory at lower flow rates. Given the limitations with synthetic materials alone, a biological or bio-hybrid vascular prosthesis could provide us with the ideal blood-vessel substitute.

FDG-PET and FDG-PET/CT for Diagnosing Infection in Patients with Multiple Vascular Bypass Grafts: A Report of Two Cases

2-Deoxy-2-[ 18 F]fluoro- d -glucose (FDG) positron emission tomography (PET) is an established imaging modality in the fields of clinical oncology, cardiology and neurology, and could be useful for the diagnosis of vascular prosthetic graft infection. The technology of combining FDG-PET and computed tomography (CT) images, acquired in a single session, is gaining popularity. Several reports proposed the application of both FDG-PET and FDG-PET/CT in the diagnosis and management of vascular prosthetic graft infection. This case report highlights the usefulness of FDG-PET and FDG-PET/CT as noninvasive diagnostic modalities for patients with multiple vascular prosthetic bypass grafts susceptible for infection.

FDG-PET and FDG-PET/CT for Diagnosing Infection in Patients with Multiple Vascular Bypass Grafts: A Report of Two Cases

FDG-PET and FDG-PET/CT for Diagnosing Infection in Patients with Multiple Vascular Bypass Grafts: A Report of Two Cases

The use of commercially available antibodies in the study of vascular disease using a porcine model

The long-term success of vascular bypass graft surgery is greatly compromised by the formation of intimal hyperplasia. An established porcine model was used to investigate the pathology and mechanism resulting in intimal hyperplasia. The aim of this study was to test the specificity of several commercially available antibodies to characterise intimal hyperplasia morphology and its immunological aspects within a porcine model. After bilateral jugular vein graft into the carotid arteries in 12 pigs, vein grafts were harvested at specific time points post-surgery and fixed in 10% neutral buffered formal saline before being embedded in paraffin wax. Five-micrometer sections were cut and subjected to routine histological and immunohistochemical techniques using the ABC method. The following antibodies were tested: von Willebrand factor (vWF), CD31 markers, smooth muscle actin (α-SMC), tissue factor (TF), CD3, two CD45 markers, CD133, NFκ-β and CD68. Results showed that labelled cells were observed with vWF, α-smooth muscle actin, TF, one CD45 marker, CD3 and CD68 within the porcine model. Sections labelled with CD133 were observed in test tissue but not within the intimal hyperplasia. No positivity was observed with either CD31 markers, one vWF or one CD45 marker. In conclusion, although commercially available antibodies may not necessarily be listed as porcine specific, by using different antigen retrieval techniques, satisfactory results can be achieved.

CT Angiography of Lower Extremity Vascular Bypass Grafts

Over the past several years computed tomography (CT) technology has advanced to such a degree that CT angiography (CTA) has become the study of choice at our institution for imaging lower extremity vascular bypass grafts. CTA quickly provides anatomic information about the state of the graft and identifies virtually all forms of bypass graft failure and related complications. Furthermore, detailed vascular anatomy is seen beyond the graft and affords sufficient anatomic detail for surgical revision without the need for other angiographic studies. Although catheter angiography, duplex-ultrasound, magnetic resonance angiography, and nuclear medicine studies all continue to play some role in the evaluation of vascular grafts, they are more often used as problem solving modalities when CTA findings are equivocal. Whereas it was once essential to catheterize directly through a failing bypass graft or pass catheters into the graft from a distant arterial puncture to obtain an angiogram of a failing bypass graft, CTA produces arteriograms with only intravenous contrast administration, a brief visit to the CT scanner, and return to daily activities without catheterization, discomfort, or risk to the bypass conduit.

Heparin-PF4 Antibodies Are Frequent after Vascular Surgery, but Not a Frequent Cause of Graft Thrombosis or Thrombocytopenia.

Surgical intervention for atherosclerotic disease of the aortoiliac and femoral-popliteal arteries has significantly reduced the incidence and complications of peripheral ischemia. However, surgical correction of obstructive arterial lesions can be complicated by either early graft failure due to acute thrombosis or late stenosis of the vascular bypass graft. Despite improvements in surgical technique, early graft failure is still observed in up to 10% of patients and up to 30 % can subsequently develop a graft stenosis. The etiology of early graft closure is less clearly understood. Anatomic or structural defects in the new graft may result in early thrombosis. Underlying prothrombotic conditions have also been suggested as contributing factors to early graft thrombosis. Recently, we have observed recurrent thrombotic events occurring in vascular grafts in two patients who were subsequently diagnosed with the syndrome of Heparin-Induced Thrombocytopenia. Because of these events we undertook an IRB approved, prospective evaluation of HIT antibodies in patients undergoing vascular surgery. Patients undergoing infra-inguinal bypass surgery for atherosclerotic vascular disease were enrolled after informed consent. Blood samples were obtained the day before surgery, day of hospital discharge, at days 14 and 28 after surgery. Platelet counts were obtained on the day of discharge and on post-surgery day 14. Plasma samples were assayed for PFA-heparin antibodies by ELISA (Stago Diagnostica) and platelet activating antibodies by platelet aggregometry. All assays were performed in duplicate.Seventy-nine patients were enrolled. Six (7.7%) patients provided only the pre-surgical blood specimen and only 68 (86%) patients provided all four blood specimens. All but 5 patients reported previous heparin exposure. Of the 73 patients in which post-surgical blood samples were taken, 28 (38%) became ELISA positive for PF4-Heparin antibodies. When tested for platelet activating antibodies, 7 (10%) were positive. All patients who developed a positive ELISA had antibody detected by day 14. Four patients tested positive by ELISA prior to surgery, with 3/4 having positive aggregation assays. One ELISA negative patient developed early graft closure. No patient developed thrombocytopenia or a 50% or greater decrease in platelet count. Patients undergoing vascular surgery frequently develop PF4-Heparin antibodies of which up to 10% patients have platelet activating antibodies. However, both thrombocytopenia and vascular graft thrombosis due to HIT is a rare event.

Extracranial-intracranial bypass for the treatment of cavernous sinus aneurysms

The optimal management of symptomatic cavernous sinus aneurysms remains controversial. Carotid occlusion is a simple procedure, but carries an ongoing risk of early and late stroke. Cerebral revascularisation is technically demanding and carries a risk of morbidity and mortality of around 10%. Eight patients treated with an extracranial-intracranial vascular bypass graft over a period of 44 months for symptomatic cavernous sinus aneurysms are reviewed. At a mean follow-up of 20 months, seven patients (87.5%) had an excellent outcome (Glasgow Outcome Score 5) while one patient suffered a perioperative stroke. In only one case, where the radial artery had been used, the graft became occluded. The results of this series seem to indicate that cerebral revascularisation is an effective treatment for patients with symptomatic cavernous sinus aneurysms.

Critical parameter of burst pressure measurement in development of bypass grafts is highly dependent on methodology used

Because of the low patency rate of currently available vascular bypass grafts, researchers are working towards the development of alternative bypass grafts, ranging from synthetic prostheses to wholly biologic living grafts. The philosophy of measurement required by regulatory agencies such as the United States Food and Drug Administration (FDA) as well as to gain the Conformité Européene (CE) mark is to test above and beyond the limits that would be expected physiologically. The critical parameter of burst pressure is needed for Conformité Européene (CE) mark or United States Food and Drug Administration (FDA) approval before clinical trials can proceed. An accurate measurement of burst pressure in potential porous vascular bypass grafts is, therefore, of utmost importance to ensure adequate strength on implantation in animals and subsequent clinical use. A wide range of methods to measure burst pressure have been used. We tested the burst pressure of a new polyurethane-based nanocomposite vascular prosthesis by using different methods to assess whether the method used affected the results. Water was infused at flow rates of 0.2, 50, and 100 mL/min through a syringe pump into latex sleeve-lined porous prostheses manufactured from a poly(carbonate-urea)urethane nanocomposite incorporating silsesquioxane. At the lowest infusion rate, the inflation was done with and without a nonporous inner lining sleeve. A pressure transducer was used to record the peak pressure achieved. Using a nonporous sleeve resulted in a higher burst pressure (428 mm Hg vs 341 mm Hg) at a flow rate of 0.2 mL/min. A lower infusion rate (0.2 mL/min) produced a lower burst pressure than 50 mL/min (428 mm Hg vs 451 mm Hg). No significant difference was found in burst pressure using infusion rates of 50 mL/min and 100 mL/min. The use of a nonporous sleeve removes the potential weakness presented by the pores themselves. A continuous high infusion rate consistently overestimates burst pressure. These methods may not reflect the physiologic state. Care needs to be taken in interpretation of methodology for burst pressure measurement, and the rate of infusion should be stated in any description of the method. The poor patency of small-caliber vascular bypass prostheses has stimulated a large body of research into alternative graft materials. This includes synthetic and, more recently, tissue-engineered hybrid products. Acceptance for international standards requires demonstration of a rigorous mechanical testing regimen, including graft strength, which has on the whole involved burst strength measurement. However, the methods used to measure burst strength have varied with respect to apparatus used and rate of graft inflation. We show that these variables lead to markedly different results. In particular, fast infusion rates may overestimate the actual burst pressure, leading to a false sense of security.

Incorporation of a lauric acid‐conjugated GRGDS peptide directly into the matrix of a poly(carbonate‐urea)urethane polymer for use in cardiovascular bypass graft applications

Gly-Arg-Gly-Asp-Ser (GRGDS) was modified by conjugation to lauric acid (LA) to facilitate incorporation into the matrix of a poly(carbonate-urea)urethane (PCU) used in vascular bypass grafts. GRGDS and LA-GRGDS were synthesized using solid phase Fmoc chemistry and characterized by high performance liquid chromatography and Fourier transform infrared spectroscopy. LA-GRGDS was passively coated and incorporated as nanoparticle dispersion on the PCU films. Biocompatibility of the modified surfaces was investigated. Endothelial cells seeded on LA-GRGDS coated and incorporated PCU showed after 48 h and 72 h a significant (p < 0.05) increase in metabolism compared with unmodified PCU. The platelet adhesion and hemolysis studies showed that the modification of PCU had no adverse effect. In conclusion, LA-conjugated RGD derivatives, such as LA-GRGDS, that permit solubility into solvents used in solvent casting methodologies should have wide applicability in polymer development for use in coronary, vascular, and dialysis bypass grafts, and furthermore scaffolds utilized for tissue regeneration and tissue engineering.

Tissue engineering of blood vessels

Tissue engineering techniques have been employed successfully in the management of wounds, burns and cartilage repair. Current prosthetic alternatives to autologous vascular bypass grafts remain poor in terms of patency and infection risk. Growing biological blood vessels has been proposed as an alternative. This review is based on a literature search using Medline, PubMed, ISIS and CAS of original articles and reviews, and unpublished material and abstracts. Complete incorporation into host tissues and the maintenance of a viable and self-renewing endothelial layer are the fundamental goals to be achieved when developing a tissue-engineered blood vessel. Sourcing of cells and modulating their interaction with extracellular matrix and supporting scaffold have been the focus of intense research. Although the use of tissue-engineered blood vessels in humans is so far limited, advances in our knowledge of stem cell precursors and the development of new biomaterials should enable this technology to reach routine clinical practice within a decade.

Internal Arteriovenous Fistula Within a Radial Forearm Flap – A Novel Technique to Increase Femorodistal Bypass Graft Flow to the Diabetic Foot and Flap Covering Ischaemic Tissue Loss

Background The fascio-cutaneous radial forearm flap is especially suitable to rebuild the contour of the foot, but because of low natural low flow this flap lacks the beneficial effect of large muscle flaps on bypass graft flow. The aim of this study was to introduce a novel technique of flap coverage combined to vascular bypass: an internal av-fistula was created within a radial forearm flap. Methods Nine critically ischaemic limbs were treated with a modified radial forearm flap in the Department of Plastic and Vascular Surgery, Helsinki University Central Hospital 1998–2003. All the patients were candidates for a major amputation unless this combined operation was attempted. A two-team approach was used: the vascular surgeon performed the distal bypass and the radial forearm flap was raised by the plastic surgeon. In eight cases a femorodistal bypass was performed and in the ninth the vein graft supplied the flap directly. The internal fistula within the flap was created between the distal end of the radial artery and either the cephalic vein or the concomitant vein of the radial artery. Flow was measured during surgery. Results Vein graft flow increased significantly after the radial forearm flap anastomosis (76 vs 44 ml/min, p=0.016). The flow of both the bypass graft and the flap artery were higher with the av-fistula patent ( p=0.016 and p=0.004). Graft patency was 89% at 2 years. Infection was a major cause of amputation, 1- and 2-year limb salvages being 67 and 53%. Conclusion In a group of diabetic patients increased flow in a vascular bypass graft was achieved by an internal av-fistula within a radial forearm flap. This method is useful in selected cases with poor run off and large ischaemic lesions.

The Clinical Use and Immunologic Impact of Thrombin in Surgery

Thrombin is a naturally derived enzyme that has been widely characterized for its roles in hemostasis, inflammation, and cell signaling. Thrombin has been purified from numerous sources and used as a clinical aid for topical hemostasis for more than 60 years. Due to both its ease of use and apparent effectiveness, thrombin has become used routinely as an aid for topical hemostasis in nearly all types of surgical procedures, including but not limited to cardiovascular, orthopedic, neurologic, general, gynecologic, and dental procedures. Due to the widespread acceptance of thrombin in the surgical setting, it is conservatively estimated that at least 1 million patients in the United States are treated with topical applications of thrombin each year. Although the U.S. Food and Drug Administration (FDA) has approved a wide array of topical and biologic products to stop surgical bleeding, the only thrombin that is currently FDA approved as a stand-alone hemostatic product in the United States is derived from bovine sources. Bovine-derived thrombin has potent biologic activity in its ability to convert fibrinogen to fibrin, activate platelets, and induce vascular contraction. However, it has also been shown to induce a robust immune response following human exposure. Numerous reports have documented an array of clinical events that follow bovine thrombin exposure, which include the development of antibodies against thrombin, prothrombin, factor V, and cardiolipin. In some well-described cases, these antibodies have led to clinical syndromes that range from severe postoperative bleeding to high rates of vascular bypass graft thrombosis. Furthermore, experimental applications of bovine thrombin to various strains of mice have induced a postexposure autoimmune syndrome that was pathologically identical to lupus. Thrombin-derived products are well accepted by the surgical community for use as an aid for hemostasis, but the bovine-derived products have an unacceptably high and unnecessary association with immunologic side effects. If a nonimmunologic and effective thrombin were developed, one would expect it to be rapidly adopted by the clinical community.