Comparison of the resistance to infection of intestinal submucosa arterial autografts versus polytetrafluoroethylene arterial prostheses in a dog model

Purpose: Prosthetic graft infection represents a most challenging complication to the vascular surgeon. Although expanded polytetrafluoroethylene (ePTFE) grafts have an acceptable patency rate, especially in the large-diameter arterial location, bacterial contamination of this material usually requires surgical removal of the graft.Methods: We compared the resistance of large-diameter ePTFE grafts and grafts constructed of small intestinal submucosa (SIS) to deliberate infection with Staphylococcus aureus. Eighteen dogs were divided into two equal groups, and the infrarenal aorta was replaced with either ePTFE or SIS graft material. One hundred million S. aureus organisms were deposited directly on the graft at the time of surgery, and the dogs were observed for 30 days.Results: One dog with an ePTFE graft died of hemorrhage from an anastomosis site at 21 days. Of the remaining eight dogs with ePTFE grafts, four had positive culture results from the removed graft material, and all had histologic evidence for persistent infection. These dogs also had chronic fever, and the average white blood cell count at day 30 was 15,600/mm³. All nine dogs with SIS grafts had patent grafts, were afebrile after the first week, had an average white blood cell count of 11,500/mm³ at 30 days (p value = NS), had negative culture results, and had the histologic appearance of graft remodeling with collagen that was free of active inflammation.Conclusions: We conclude that large-diameter arterial SIS grafts are more resistant to persistent infection with S. aureus than ePTFE grafts in this dog model of deliberate bacterial inoculation. (J VASC SURG 1994;19:465-72.)     

The effect of bacterial contamination on neointimal hyperplasia in vascular grafts

Neointimal hyperplasia (NH) is the most significant contributing factor to long-term vascular graft failure. Inflammation is known to be important in its development; however, the role of bacterial infection is unclear. We examined the effect of contamination with common organisms on the development of NH in expanded polytetrafluoroethylene grafts. Thirty adult pigs were randomized into one of four groups: no infection, contamination with Staphylococcus aureus, mucin-producing Staphylococcus epidermidis, or Pseudomonas aeruginosa. An expanded polytetrafluoroethylene graft (6 mm x 3 cm) was placed as a common iliac artery interposition graft and was inoculated with 1-2 x 10(8) of the selected organism before closure. Grafts were explanted 6 weeks postoperatively. Microbiologic, histological, and morphometric evaluations were performed. All grafts were patent at the time of euthanasia. The mean areas of NH were 5.45 mm(2) in sterile grafts, 8.36 mm(2) in S. aureus, 7.63 mm(2) in S. epidermidis, and 11.52 mm(2) in P. aeruginosa grafts. Comparison of means via analysis of variance showed that P. aeruginosa grafts had significantly higher formation of NH than sterile grafts (P = 0.025). NH production in infected grafts appears to be organism specific and is significantly higher with P. aeruginosa than common Gram-positive organisms. Increased NH from subclinical infection may be a significant factor contributing to late graft failures.     

Small-caliber heparin-coated ePTFE grafts reduce platelet deposition and neointimal hyperplasia in a baboon model

PURPOSE: Intimal hyperplasia and graft thrombosis are major causes of graft failure. Heparin prolongs graft patency and inhibits neointimal hyperplasia in animal models. The purpose of this study was to evaluate the effect of a heparin-coated expanded polytetrafluoroethylene (ePTFE) graft on platelet deposition and anastomotic neointimal hyperplasia after aortoiliac bypass grafting in a baboon model. METHODS: Heparin-coated ePTFE grafts (4-mm diameter) were incorporated into exteriorized femoral arteriovenous shunts placed in five baboons. Platelet deposition was analyzed by measuring the accumulation of indium 111-labeled platelets on the grafts, with dynamic scintillation camera imaging. Eight adult male baboons (mean weight, 9.3 kg) underwent bilateral aortoiliac bypass grafting with ePTFE grafts (4-mm internal diameter). In each animal a heparin-coated ePTFE graft was placed in one aortoiliac artery, and an uncoated graft, which served as the control, was placed in the contralateral aortoiliac artery. All grafts were harvested at 4 weeks, and were analyzed quantitatively for neointimal hyperplasia at graft-vessel anastomoses. RESULTS: Early platelet deposition on heparin-coated grafts after 1 to 4 hours of ex vivo circuitry was significantly reduced. All the harvested aortoiliac grafts were patent at 4 weeks. There was a significant reduction in neointimal area at both proximal (0.26 +/- 0.11 mm(2)) and distal (0.29 +/- 0.14 mm(2)) anastomoses in the heparin-coated grafts, compared with proximal (0.56 +/- 0.18 mm(2)) and distal (0.63 +/- 0.21 mm(2)) anastomoses in the untreated control grafts (P <.05). In addition, neointimal cell proliferation assayed with bromodeoxyuridine (BrdU) incorporation was reduced in the graft neointima (3.47% +/- 0.43%) in heparin-coated grafts compared with the graft neointima (6.21% +/- 0.59%) in untreated control grafts (P <.05). CONCLUSIONS: Small-caliber heparin-coated ePTFE grafts significantly reduce platelet deposition and anastomotic neointimal hyperplasia and cell proliferation, without measurable side effects, in baboons. Surface coating with heparin in small-caliber ePTFE grafts is useful for improving prosthetic bypass graft patency. Clinical relevance: An autologous vein graft is the ideal bypass conduit in peripheral arterial reconstruction; however, many patients who undergo bypass grafting do not have adequate or available autologous vein graft. As a result surgeons often must rely on prosthetic grafts as an alternative conduit in arterial bypass procedures. Clinical outcomes with prosthetic grafts in peripheral arterial reconstruction are generally inferior to those with autologous vein bypass grafts, in part because of anastomotic neointimal hyperplasia. This study evaluated the effect of small-caliber heparin-coated expandable polytetrafluoroethylene (ePTFE) grafts in aortoiliac reconstruction in a baboon model. The study found that heparin-coated ePTFE grafts resulted in less intimal hyperplasia and less platelet deposition after implantation, compared with noncoated control ePTFE grafts.     

Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased anastomotic neointimal hyperplasia in a porcine model

OBJECTIVE: We tested the hypothesis that rapamycin coated onto, and eluted from, expanded polytetrafluoroethylene (ePTFE) grafts would diminish neointimal hyperplasia in a porcine model. METHODS: Rapamycin (also called sirolimus) was coated onto the luminal surface of 6-mm-internal-diameter thin-walled ePTFE grafts by using an adhesive polymer that allows timed release of the drug. An adhesive polymer that allows timed release of rapamycin from ePTFE was developed with commercially available chemicals and applied on 6-mm ePTFE grafts. Graft integrity was characterized by scanning electron microscopy, and rapamycin levels were quantified by using high-performance liquid chromatography. Twenty-two mongrel pigs were randomized into three groups: untreated ePTFE (n = 6), adhesive-only coated ePTFE (n = 6), or adhesive- and rapamycin-coated ePTFE (n = 10). End-to-side unilateral aortoiliac bypasses were performed by using 6-mm-internal-diameter ePTFE grafts and standardized anastomotic lengths. Unilateral end-to-side aortoiliac ePTFE grafts (6-mm internal diameter) were inserted by using polypropylene sutures, 6-0 proximally and 7-0 distally; all anastomoses were 12 mm long. All animals received aspirin (325 mg orally) daily. All animals were given oral aspirin (325 mg) daily beginning on the day before surgery. At 28 days, the animals were killed, and the grafts were explanted in continuity with the adjacent aortic cuff and the outflow iliac artery. Variables compared between groups included graft patency, distal anastomotic length and cross-sectional narrowing, and intimal thickness at the arterial-graft junction indexed to the adjacent graft thickness. Microscopic analysis was performed with hematoxylin and eosin and Masson trichrome stains on paraffin sections. A pathologist blinded to experimental groups graded sections for collagen deposition, neointima formation, inflammatory cellular infiltrates, medial necrosis, and aneurysmal degeneration. RESULTS: All animals survived until they were killed without clinical evidence of limb ischemia or graft infection. Preplanned t tests in the context of one-way analysis of variance showed no difference in outcome measures between the untreated ePTFE and adhesive-only coated ePTFE groups; therefore, they were combined in further comparisons with the adhesive- and rapamycin-coated ePTFE group. The Rapamycine eluting expanded polytetrafluoroethylene group had longer anastomoses (85.6% vs 60.6% of the initial anastomotic length maintained; P < .0001) and less cross-sectional narrowing in the outflow graft (16.2% vs 28.5%; P = .0007) when compared with the other two groups by using two-tailed Student t tests. There was no evidence of medial necrosis or aneurysmal degeneration. All patent grafts had complete endothelialization on hematoxylin and eosin sections. Rapamycin was detectable and quantifiable in the arterial wall at 28 days after implantation. CONCLUSIONS: Rapamycin can be coated onto and eluted from ePTFE by using a nonionic polymer and a simple coating technique. At 4 weeks after implantation, the rapamycin-eluting ePTFE grafts demonstrate gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with non-drug-eluting ePTFE. Four weeks after implantation in a porcine model, rapamycin-eluting ePTFE grafts demonstrated gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with untreated and adhesive-only coated ePTFE grafts. CLINICAL RELEVANCE: Rapamycin-eluting ePTFE grafts decrease neointimal hyperplasia in a porcine model. Further studies are needed to evaluate whether patency will be improved. Rapamycin-eluting ePTFE grafts may allow the use of prosthetic grafts in situations in which autologous vein is unavailable and in which neointimal hyperplasia is pronounced, such as in small-diameter (<6-mm) vessels typical of infrapopliteal interventions.     

TIMP-2 modulates neointimal formation in experimental ePTFE arterial grafts

BACKGROUND: In vascular reconstructive surgery, myointimal hyperplasia contributes to the adverse outcome of synthetic grafts. This phenomenon is because of unregulated extracellular matrix degradation and remodeling, and excessive smooth muscle cell proliferation and migration. Matrix metallopreoteinase 2 (MMP-2) is known as an important contributor to these events. The aims of our study was to investigate the effects of selective MMP-2 inhibitor (TIMP-2) in endothelialization rate, SMC proliferation, and myointimal hyperplasia in experimental ePTFE arterial grafts. METHODS: In 20 male Lewis rats, a 1-cm long ePTFE graft has been inserted at the level of the abdominal aorta. Animals were randomized in two groups (10 animals each): group A received six subcutaneous inoculations of TIMP-2 (2.5 microg) after surgery, group B received only the vehicle of TIMP-2. RESULTS: Neointimal thickness, as well as SMC density, were augmented in group B, whereas endothelial cells density was augmented in group A, and these findings were statistically significant. In group A SMC were better organized, just like SMC of thoracic aorta. In group B SMC were no organized. Furthermore, anti-TIMP-2 and anti-MMP-2 coloration revealed higher levels of TIMP-2 and lower levels of MMP-2 in group A versus group-B. CONCLUSIONS: Use of TIMP-2 affects the neointimal formation of experimental e-PTFE arterial grafts, leading to a better-organized neointima, with improved endothelialization.     

Improved Healing of Small-Caliber,Long-Fibril Expanded Polytetrafluoroethylene Vascular Grafts by Covalent Bonding of Fibronectin

Purpose To evaluate the intermediate performance of small-caliber, long-fibril expanded polytetrafluoroethylene (ePTFE) vascular grafts pretreated with covalent bonding of fibronectin in dogs.Methods Small-caliber (4mm), long-fibril (60µm), ePTFE vascular grafts, 10cm in length, were pretreated by covalent bonding of fibronectin. Bilateral iliac grafting was done in dogs using a fibronectin-bonded graft on one side and a nonbonded control graft on the other side. The grafts were retrieved 12 weeks after implantation, and subjected to histomorphometric analysis.Results Although the patency rates of the fibronectin-bonded and control grafts were the same (3/7, 43%), the fibronectin-bonded grafts showed almost complete neointimal healing, whereas the nonbonded control grafts showed only partial neointimal healing, proximally and distally.Conclusions Small-caliber, long-fibril ePTFE vascular grafts with covalent bonding of fibronectin achieved almost complete neointimal healing by the time of retrieval at 12 weeks. This indicates that, with further modifications, our new technique for covalent bonding of fibronectin has great potential in the development of small-caliber arterial prosthetic grafts.     

Small intestinal submucosa for vascular reconstruction in the presence of gastrointestinal contamination

INTRODUCTION: Surgical options for vascular reconstruction in a contaminated field are limited and include prosthetic reconstruction or ligation with extra-anatomic bypass. With prosthetic insertion, rates of graft infection and failures (pseudoaneurysms and thrombosis) are high. In the emergent situations, extra-anatomic bypass is time-consuming and complex, and it produces marginal long-term results. Small intestinal submucosa (SIS) is a cell-free collagen matrix derived from porcine small intestine. Preliminary studies have demonstrated its ability to be remodeled into host tissue. In this study, we compared SIS to polytetrafluoroethylene (PTFE) as a vascular patch for arterial repair in the presence of massive gastrointestinal contamination to evaluate graft patency, incorporation, infection, and aneurysm formation. METHODS: Adult mongrel pigs underwent general anesthesia with Isoflurane and were then randomized to 1 of 3 groups: control, contamination (colon puncture with stool contamination of the pelvis), or shock + contamination (40% blood volume for 1 hour, then resuscitation with shed blood and crystalloid, plus contamination). All groups then underwent a left common iliac arteriotomy and further randomized to a 1 x 3-cm patch angioplasty with either SIS or PTFE. All received cefotetan for 24 hours. All animals were sacrificed between 2 and 4 weeks, and necropsy was performed. Grafts were cultured, and microscopic analysis with hematoxylin and eosin and trichrome was performed. Outcomes included pulse quality (normal or diminished) compared with opposite side, graft infection, and pseudoaneurysm; all were determined by a blinded investigator. RESULTS: Forty animals were randomized, and 1 died of abdominal sepsis. All control animals had normal distal pulses, no pseudoaneurysms, and no patch infections. The pseudoaneurysm rate for the contaminated PTFE patches was 25% compared with 0% in the SIS group (P = 0.09). Patch infection occurred in 73% of all PTFE patches compared with 8% of SIS patches (P < 0.03). Organisms present in the infected grafts included Escherichia coli, Bacteroides species, and other Gram-negative enterics. Histopathology demonstrated the presence of neointima in both SIS and PTFE. Only SIS was completely incorporated, with infiltration of collagen fibrils and lymphocytes. CONCLUSIONS: SIS was associated with improved graft patency, less infection, complete incorporation, and no false aneurysm formation when compared with PTFE. This may be due to its ability to provide a durable scaffold for cellularization and tissue remodeling. This material may offer a superior alternative to more complex vascular reconstruction techniques in contaminated fields.     

Evaluation of platelet deposition and neointimal hyperplasia of heparin-coated small-caliber ePTFE grafts in a canine femoral artery bypass model

INTRODUCTION: Bypass graft failure due to acute thrombosis and intimal hyperplasia remains a major challenge in small-diameter vascular prosthetic graft reconstruction. Heparin has been shown to prevent thrombus formation and inhibit intimal antithrombotic in animal studies. In this study, we evaluated the effect of small-caliber heparin-coated expanded polytetrafluoroethylene (ePTFE) grafts on platelet deposition and intimal hyperplasia in a canine model of femoral artery bypass grafting. METHODS: Nine adult greyhound dogs underwent placement of bilateral femorofemoral artery bypass grafts with ePTFE grafts (4 mm diameter and 7 cm long). In each animal, a heparin-coated ePTFE graft was placed on one side while a noncoated graft was placed on the contralateral side which served as the control. Platelet deposition was measured by autologous (111)indium-labeling and scintillation camera imaging analysis in 24 h. The graft patency was assessed at 4 weeks following the bypass. The effect of intimal hyperplasia was assessed with histological and morphometric analysis. RESULTS: Platelet deposition on the heparin-coated grafts at 24 h was significantly reduced by 72% as compared to controls (P = 0.001). The patency rate was 44% in control grafts and 89% in heparin-coated grafts. There was a significant reduction of graft intimal hyperplasia at both proximal (0.38 +/- 0.21 mm(2)) and distal (0.19 +/- 0.06 mm(2)) anastomoses in the heparin-coated grafts as compared with proximal (1.01 +/- 0.28 mm(2)) and distal (0.42 +/- 0.01 mm(2)) anastomoses in the untreated control grafts, respectively (P < 0.05). Heparin coating significantly reduced graft neointimal hyperplasia at patent graft anastomoses by 55-72% as compared to controls. CONCLUSIONS: These data demonstrate that heparin coating of ePTFE significantly reduced early platelet deposition and inhibited anastomotic neointimal hyperplasia. Moreover, small-caliber heparin-coated ePTFE graft significantly increased graft patency in a canine femoral artery bypass model. This may represent a promising treatment strategy for improving the clinical performance of small-caliber prosthetic vascular grafts.     

Studies in thoracic aortic graft infections: the development of a porcine model and a comparison of collagen-impregnated dacron grafts and cryopreserved allografts.

OBJECTIVE: A porcine model of thoracic aortic graft infection was created, and various anatomic sites and the timing of inoculation of the graft to induce infection were investigated. Ultimately, the ability of cryopreserved allograft to resist infection was compared with that of collagen-impregnated Dacron graft. METHODS: Yorkshire pigs (n = 16) underwent placement of an expanded polytetrafluoroethylene patch graft in the ascending aorta and the left atrial appendage (phase I). Eight animals were immediately given a 50-mL bolus (1 x 10(8) cfu/mL) of Staphylococcus aureus whereas the other 8 received the infusion 24 hours later. Animals were put to death 8 weeks later and the grafts were sterilely explanted and analyzed via microbiologic culture and standard histologic procedures for evidence of infection. The results displayed that the aortic graft and a delay of induced bacteremia of 24 hours were more reliable methods of producing infection. During phase II, 13 pigs were randomized to receive either a collagen-impregnated Dacron graft (n = 6) or a cryopreserved allograft (n = 7) in the ascending aortic position only and infusion of S aureus 24 hours after the operation. The experiment then proceeded to completion. RESULTS: Phase I results displayed that use of an aortic graft and induced bacteremia 24 hours after the operation was a more reliable and reproducible method of producing infection. In phase II, graft infection was present in 38.5% (5/13) of animals, with only 16.7% (1/6) in the collagen-impregnated Dacron graft group and 57.2% (4/7) in the cryopreserved allograft group becoming infected. There was no significant difference between the collagen-impregnated Dacron graft and cryopreserved allograft groups in the incidences of thoracic aortic graft infections (P =.27, Fisher exact test). CONCLUSIONS: This novel porcine model of thoracic aortic graft infection is a reproducible method for the investigation of thoracic aortic graft infections. The phase I study investigated the timing of the induced bacteremia and the most susceptible position of a graft. Phase II demonstrated that collagen-impregnated Dacron grafts are equivalent, if not superior, to cryopreserved allografts in resisting central vascular graft infections in the ascending aorta.     

Dual role of VEGF in pretreated experimental ePTFE arterial grafts

BACKGROUND: Lack of endothelialization and abnormal smooth muscle cell (SMC) growth adversely affect the outcome of vascular synthetic grafts. The aims of our study were to investigate how a coating of extracellular matrix (ECM) and vascular endothelial growth factor (VEGF) might affect the endothelialization rate, smooth muscle cells (SMC) proliferation, and myointimal hyperplasia in experimental arterial ePTFE grafts. METHODS: In each of 30 male Lewis rats, a 1-cm-long ePTFE graft was inserted at the level of the abdominal aorta. Animals were randomized in five groups (six animals each): groups A and A1 received ePTFE grafts coated with a synthetic extracellular matrix (growth factor-reduced matrigel) containing VEGF; groups B and B1 received ePTFE grafts coated with synthetic ECM; and group C received ePTFE grafts alone. The grafts were explanted at 30 days from surgery for immunohistochemical analysis. RESULTS: Both endothelialization rate and myointimal hyperplasia were augmented in group A versus groups B and C, and these findings were statistically significant. SMC density resulted significantly higher in group A versus groups B and C, and this was associated with an altered expression of bFGF and TGFbeta. CONCLUSIONS: Pretreating ePTFE grafts with synthetic ECM and VEGF results in better endothelialization, but also in undesired higher SMC density and myointimal hyperplasia.     

The prophylactic efficacy of rifampicin-soaked graft in combination with systemic vancomycin in the prevention of prosthetic vascular graft infection: an experimental study

OBJECTIVE: To investigate the prophylactic efficacy of systemic, topical, or combined antibiotic usage in the prevention of late prosthetic vascular graft infection caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and the differential adherence of S. epidermidis to Dacron and ePTFE grafts in a rat model. MATERIALS AND METHODS: Graft infections were established in the back subcutaneous tissue of 120 adult male Wistar rats by implantation of 1-cm(2) Dacron/ePTFE prosthesis followed by topical inoculation with 2 x 10(7) CFU of clinical isolate of MRSE. Each of the series included one group with no graft contamination and no antibiotic prophylaxis (uncontaminated control), one contaminated group that did not receive any antibiotic prophylaxis (untreated control), one contaminated group in which perioperative intraperitoneal prophylaxis with vancomycin (10 mg/kg) was administered, two contaminated groups that received rifampicin-soaked (5 mg/1 ml) or vancomycin-soaked (1 mg/1 ml) grafts, and one contaminated group that received a combination of rifampicin-soaked (5 mg/1 ml) graft with perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg). The grafts were removed sterilely 7 days after implantation and evaluated by using sonication and quantitative blood agar culture. RESULTS: MRSE had significantly greater adherence to Dacron than ePTFE grafts in the untreated contaminated groups (P < 0.001). Rifampicin had better efficacy than vancomycin in topical application, but the difference was not statistically significant (P > 0.05). Intraperitoneal vancomycin showed a significantly higher efficacy than topical vancomycin or rifampicin (P < 0.001). The best results were provided by a combination of intraperitoneal vancomycin in rifampicin-soaked graft groups (P < 0.001). CONCLUSIONS: The combination of rifampicin and intraperitoneal vancomycin seems to be the best choice for the prophylaxis of late prosthetic vascular graft infections caused by MRSE.     

Multicenter evaluation of a polytetrafluoroethylene vascular access graft as compared with the expanded polytetrafluoroethylene vascular access graft in hemodialysis applications

OBJECTIVES: The purpose of this study was to compare in a randomized, prospective, and controlled study, the performance of a multilayered, self-sealing polyurethane vascular access graft (PVAG) and expanded polytetrafluoroethylene (ePTFE) vascular access grafts in hemodialysis applications. Performance measures included graft survival, complications, time to early cannulation, and hemostasis times after cannulation.Study Design: A total of 142 patients were randomized equally to receive one of the two grafts after meeting all eligibility requirements. All patients were followed up prospectively to 12 months or to the end of secondary patency. Specifically, this study documented the performance of the PVAG and ePTFE grafts by determining the patencies and complications for both grafts. RESULTS: Patient characteristics between the two groups were similar with respect to risk factors and demographic characteristics (P >.05). Life-table patencies from the date of first dialysis were primary patency: PVAG 55% versus ePTFE 47% (6 months) and PVAG 44% versus ePTFE 36% (12 months) and secondary patency: PVAG 87% versus ePTFE 90% (6 months) and PVAG 78% versus ePTFE 80% (12 months). None of these differences were significant (P >.05). Both primary and secondary patencies were also not significantly different when the date of implantation was the starting point. Adverse events and complications were similar for the two groups, except the PVAG group had a higher incidence of technical complications manifested by graft kinking when compared with the control cohort (P <.05). Additionally, there was no significant difference in complication rates between these two groups with regard to infection and bleeding. When the time to hemostasis after cannulation was compared at 5minutes or less, there were more PVAG cannulation sites that achieved hemostasis compared with ePTFE sites, and this difference was significant (P <.0001). When time to first dialysis access was compared between the two grafts, 53.9% of all PVAG grafts were cannulated before 9 days versus none with the ePTFE grafts (P <.001). However, long-term graft survival was not significantly different when PVAG patients were stratified into early (< 9 days) and the late access (9 >/= days) groups (P =.29). CONCLUSIONS: The PVAG graft allows for early access without compromising long-term performance. Both PVAG and standard ePTFE grafts have similar long-term outcomes, despite early access with the PVAG vascular access grafts.     

Platelet reactivity in human aortic grafts: a prospective, randomized midterm study of platelet adherence and release products in Dacron and polytetrafluoroethylene conduits

Platelet-related phenomena at the blood-surface interface of randomly placed knitted Dacron (n = 6) and polytetrafluoroethylene (ePTFE) (n = 6) interposition aortic grafts were studied in patients undergoing abdominal aortic aneurysmectomy. Luminal accumulation of platelets was assessed by infusing indium-111-oxine (400 microCi) labeled autologous platelets and imaging grafts at 1 week, 3 months, and 6 months after surgery. Image analysis included an indium ratio technique (comparing aortic graft radioactivity to that of an iliac artery) and a red blood cell technetium subtraction technique (excluding blood pool radioactivity from graft radioactivity, with the heart or iliac artery serving as reference regions). Plasma levels of beta-thromboglobulin and platelet factor 4 were correlated with platelet accumulations on the aortic prostheses. Differences in graft radioactivity or platelet-release products were not evident 1 week after surgery. Three months after implantation, Dacron and ePTFE conduits exhibited 87% and 47% (p less than 0.05) more radioactivity with the indium ratio technique than the iliac artery. Similarly, increased Dacron compared with ePTFE graft radioactivity was noted using technetium subtraction techniques: 71% vs 30% with a heart reference and 26% vs 11% with an iliac artery reference, respectively. Increases in graft radioactivity correlated with increases in both plasma beta-thromboglobulin and platelet factor 4 at 3 months (r = 0.6 to 0.9; p less than 0.05 to 0.001 depending on the imaging technique used). At 6 months, differences did not persist. In fact, technetium subtraction techniques suggested less Dacron conduit reactivity. It is speculated that differences in platelet accumulation and activation associated with different graft substrates may prove clinically important.     

In vivo h-VEGF165 gene transfer improves early endothelialisation and patency in synthetic vascular grafts.

OBJECTIVES: Small-diameter synthetic vascular graft performance is inferior to autologous vein grafts. This study tested the hypotheses that local in vivo administration of plasmids encoding for human vascular endothelial growth factor (VEGF), or co-administration of plasmids encoding for human vascular endothelial growth factor/plasmids encoding for fibroblast growth factor-2 in the tissues surrounding a porous synthetic vascular graft would enhance graft endothelialisation and, consecutively, graft patency. METHODS: First, optimal gene for small-diameter synthetic graft endothelialisation was studied in rat abdominal aorta model (n=132): plasmids encoding for human vascular endothelial growth factor; co-administration of plasmids encoding for human vascular endothelial growth factor/plasmids encoding for fibroblast growth factor-2; or control plasmids were injected around 60 microm ePTFE graft. Second, optimal small-diameter synthetic graft design for endothelialisation was explored in rabbit abdominal aorta model (n=90). Various ePTFE grafts or pre-clotted polyester grafts were used with/without plasmids encoding for human vascular endothelial growth factor. Third, clinically used medium-size synthetic grafts were investigated with/without plasmids encoding for human vascular endothelial growth factor in dog carotid (n=20) and femoral arteries (n=15). Endothelialisation was assessed in midgraft area with scanning electron microscopy. RESULTS: In rats, plasmids encoding for human vascular endothelial growth factor enhanced endothelialisation; whereas co-administration of plasmids encoding for human vascular endothelial growth factor/plasmids encoding for fibroblast growth factor-2 had worst outcome at 1 week (NS), 2 weeks (P=0.01) and 4 weeks (P=0.02). In rabbits, pre-clotted polyester grafts had a trend for faster endothelialisation than ePTFE grafts (P=0.08); whereas plasmids encoding for human vascular endothelial growth factor enhanced endothelialisation compared to controls at 2 weeks (P=0.06), however, the effect reversed at 4 weeks (P=0.03). In dogs, synthetic graft patency was improved by plasmids encoding for human vascular endothelial growth factor in femoral position (P=0.103); whereas all carotid grafts were patent at 6 weeks. CONCLUSIONS: Thus, these data suggested that endothelialisation was fastest in pre-clotted polyester grafts; and that local application of plasmids encoding for human vascular endothelial growth factor had a potential to improve early endothelialisation and patency in synthetic vascular grafts.     

Nonporous silicone polymer coating of expanded polytetrafluoroethylene grafts reduces graft neointimal hyperplasia in dog and baboon models

Purpose: Neointimal hyperplasia frequently develops after placement of prosthetic vascular grafts and is a major cause of graft failure. This study was an attempt to prevent vascular lesion formation by coating the graft luminal surface with a thin layer of nonporous silicone polymer, and subsequently with an ultrathin layer of vapor phase (plasma gas) deposited fluoropolymer, thereby providing a smooth and chemically uniform surface that was postulated to limit pannus tissue ingrowth across the graft anastomoses.Methods: Bilateral femoral arteriovenous (AV) conduits were constructed in four dogs using expanded polytetrafluoroethylene graft materials (ePTFE; 6-mm inside diameter, 2.5-cm long). In each animal, one femoral AV shunt was constructed from a graft whose luminal surface was entirely coated with polymer. On the contralateral side, an uncoated graft served as a control. Bilateral aortoiliac grafts were placed in three baboons using 5-cm segments of ePTFE (4-mm inside diameter). One end (1 cm) of each graft had been coated with polymer. In each animal, the coated end of one graft was placed proximally and the coated end of the second graft was placed distally in the contralateral vessels.Results: All grafts were patent at 30 days. In the dog model, there was a significant reduction in graft neointimal area at the venous anastomoses for the coated grafts compared with the uncoated grafts (0.03 ± 0.02 mm ² and 1.11 ± 0.54 mm ² , respectively; p < 0.05). In the baboon model, the silicone coating significantly reduced the graft neointimal thickness (0.003 ± 0.003 mm vs 0.21 ± 0.05 mm; p < 0.05) and neointimal area (0.05 ± 0.08 mm ² vs 0.82 ± 0.58 mm ² ; p < 0.05).Conclusions: These data demonstrate that healing of ePTFE grafts can be effectively modified by altering the physical properties of the graft surface. Neointimal hyperplasia within ePTFE grafts is significantly reduced by the local application of a fluorocarbon-coated, silicone-based polymer. The resulting graft flow surface effectively prevents tissue ingrowth from the adjacent native vessel, thereby preserving the anastomosis luminal area. This approach could represent a new strategy for limiting graft surface anastomotic neointimal hyperplasia. (J Vasc Surg 1996;24:825-33.)     

Small intestinal submucosa as a large diameter vascular graft in the dog

Autogenous saphenous vein and synthetic materials, such as Dacron and expanded polytetrafluoroethylene, have been used extensively as vascular grafts with moderate success. Improved success rates for vascular graft surgery may be possible if superior graft material was available. We tested the use of autogenous small intestinal submucosa (SIS) as a large diameter (10 mm) vascular graft in the infrarenal aorta of 12 dogs. One dog died with graft thrombosis within 48 hr of surgery. Nine dogs were sacrificed at various times during a 52-week post-surgical period and showed patent grafts without infection, thrombosis, intimal hyperplasia, or adverse effects upon blood pressure. There was no ultrastructural evidence of endothelial cell growth on the luminal surface of the SIS graft which was composed of a dense, non-thrombogenic, organized collagenous connective tissue. The SIS material was approximately one order of magnitude less elastic than natural aorta and showed an immediate dilatation of approximately 18% after exposure to the systemic blood pressure. However, there was no progressive dilatation during the 52-week postsurgical period. Two dogs remain alive at 8 and 52 weeks post-surgery with patent grafts as determined by positive contrast radiography and Doppler studies. We conclude that autogenous small intestinal submucosa can be successfully used as a large diameter arterial graft in the dog and is worthy of further investigation.     

Use of an antibiotic-bonded graft for in situ reconstruction after prosthetic graft infections.

We have developed an infection resistant vascular prosthesis by bonding rifampin to Dacron grafts with the use of a collagen matrix release system. The purpose of this study was to determine the efficacy of this antibiotic-bonded graft in resisting infection after an in situ reconstruction of a previously infected prosthetic bypass. Eighty-three adult mongrel dogs underwent implantation of a 3 cm untreated Dacron graft into the infrarenal aorta. This initial graft was deliberately infected, at the time of operation, with 10(2) organisms of Staphylococcus aureus by direct inoculation. One week later, the dogs were reexplored, the retroperitoneum debrided, and the animals randomized to undergo an end-to-end in situ graft replacement with either one of two types of prosthetic grafts: group I (collagen, n = 36) received control collagen-impregnated knitted Dacron grafts; group II (rifampin, n = 47) received experimental collagen-rifampin-bonded Dacron grafts. Each group of animals was then subdivided to receive one of four treatment protocols: (a) no antibiotic therapy, (b) cephalosporin peritoneal irrigation solution (cefazolin 500 mg/1000 ml) during operation and two doses of cephalosporin (cefazolin, 500 mg intramuscularly) postoperatively, (c) treatment as in protocol group b plus 1 week of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily), and (d) treatment as in protocol group b plus 2 weeks of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily). All grafts were sterilely removed between 3 and 4 weeks after implantation. There were no anastomotic disruptions and all grafts were patent at the time of removal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of carbon-impregnated and standard ePTFE prostheses in extra-anatomical anterior tibial artery bypass: a prospective randomized multicenter study.

OBJECTIVES: The aim of this study was to find out whether carbon impregnated ePTFE vascular grafts have better long-term patency or limb salvage rates than Standard ePTFE vascular grafts in crural revascularization in patients with chronic critical ischemia. DESIGN: Prospective randomized multicenter trial. Study endpoints were 36 months follow-up, major amputation or death. MATERIALS: We used 6mm carbon ePTFE (Carboflo) and 6mm standard ePTFE vascular grafts (both C.R. BARD Inc./IMPRA). METHODS: From June 1995 to November 1998, 283 patients were randomly assigned either to carbon (C) (n=140) or to standard (St) ePTFE (n=143) vascular grafts at 19 centres. A standard protocol was used with lateral extra-anatomic course of the graft to the anterior tibial artery and of a distal vein patch or cuff. More than 90% of the patients had rest pain or gangrene. RESULTS: Two hundred and sixty-five (C=130; St=135) patients could be analysed in the intention-to-treat (ITT) group. Primary patency, secondary patency and limb salvage rates after 36 months were 33, 43 and 67% in the carbon- and 30, 38 and 58% in the standard PTFE group, respectively, (log-rank test: p=0.20, 0.12 and 0.16). Additional analyses were made per protocol (PP) and as-treated (AT). The retrospective power of the study was calculated as 79 and 83%. CONCLUSION: The ITT, PP and AT analysis, showed no statistically significant advantage of the carbon ePTFE vascular graft in terms of patency or limb salvage over the standard ePTFE vascular graft at 36 months.     

Prevention of Staphylococcus aureus graft infection by a new gelatin-sealed vascular graft prebonded with antibiotics

OBJECTIVE: The aim of this study was to evaluate the efficacy of a new gelatin-sealed graft prebonded with two antibiotics in resisting infection with Staphylococcus aureus (S aureus) A980142 after direct bacterial application in a dog model. METHODS: Twelve 6.0-mm polyester grafts were implanted in dogs end-to-end into the infrarenal aorta. The dogs were divided into two groups. A test group (n = 6) received experimental antibiotic-bonded gelatin-sealed knitted polyester grafts, loaded with two antibiotics, rifampin and tobramycin. A control group (n = 6) received commercial gelatin-sealed knitted polyester grafts. At the end of graft implantation, 50 mul of a 1.8 x 10(4) CFU/mL S aureus solution were instilled directly over the graft. One week after implantation, grafts were harvested with sterile technique. Quantitative cultures were obtained from all the harvested grafts. The results were expressed as colony-forming units per cm(2) of surface of the graft. Bacteriological study was also performed on various tissue samples. The chi(2) test was used to compare the culture proven infection of control and antibiotics-bonded grafts. RESULTS: Mean inoculum size was similar in the two groups of dogs. Five of the six control grafts grew S aureus A980142 at the time of graft removal, whereas none of the six antibiotic-bonded gelatin-sealed grafts were infected (P = .0192). None of the organ samples were infected in the group implanted with antibiotic-bonded grafts, whereas 15/34 samples grew S. aureus in the control group. CONCLUSION: These results indicate that this gelatin sealed graft prebonded with two antibiotics resists infection caused by S aureus graft contamination in a dog model.     

Multicenter evaluation of a polyurethaneurea vascular access graft as compared with the expanded polytetrafluoroethylene vascular access graft in hemodialysis applications

Objectives: The purpose of this study was to compare in a randomized, prospective, and controlled study, the performance of a multilayered, self-sealing polyurethane vascular access graft (PVAG) and expanded polytetrafluoroethylene (ePTFE) vascular access grafts in hemodialysis applications. Performance measures included graft survival, complications, time to early cannulation, and hemostasis times after cannulation. Study Design: A total of 142 patients were randomized equally to receive one of the two grafts after meeting all eligibility requirements. All patients were followed up prospectively to 12 months or to the end of secondary patency. Specifically, this study documented the performance of the PVAG and ePTFE grafts by determining the patencies and complications for both grafts. Results: Patient characteristics between the two groups were similar with respect to risk factors and demographic characteristics (P >.05). Life-table patencies from the date of first dialysis were primary patency: PVAG 55% versus ePTFE 47% (6 months) and PVAG 44% versus ePTFE 36% (12 months) and secondary patency: PVAG 87% versus ePTFE 90% (6 months) and PVAG 78% versus ePTFE 80% (12 months). None of these differences were significant (P >.05). Both primary and secondary patencies were also not significantly different when the date of implantation was the starting point. Adverse events and complications were similar for the two groups, except the PVAG group had a higher incidence of technical complications manifested by graft kinking when compared with the control cohort (P <.05). Additionally, there was no significant difference in complication rates between these two groups with regard to infection and bleeding. When the time to hemostasis after cannulation was compared at 5 minutes or less, there were more PVAG cannulation sites that achieved hemostasis compared with ePTFE sites, and this difference was significant (P <.0001). When time to first dialysis access was compared between the two grafts, 53.9% of all PVAG grafts were cannulated before 9 days versus none with the ePTFE grafts (P <.001). However, long-term graft survival was not significantly different when PVAG patients were stratified into early (< 9 days) and the late access (9 ≥ days) groups (P =.29). Conclusions: The PVAG graft allows for early access without compromising long-term performance. Both PVAG and standard ePTFE grafts have similar long-term outcomes, despite early access with the PVAG vascular access grafts. (J Vasc Surg 2001;34:465-73.)