fibrin and Graft-Occlusion--Vascular

Although current thrombolytic agents have proven their clinical benefit, the failure to rapidly reperfuse some patients and the persistent bleeding risk represent areas for improvement in therapy. In the past two years, the field has been advanced by the regulatory approval of agents with greater ease of administration, continued development of new agents and exploration of the use of more advanced antiplatelet therapies in combination with thrombolytic agents. Finally, a new class of directly acting fibrinolytic agents is available.

Topics: Animals; Arterial Occlusive Diseases; Catheterization, Central Venous; Contraindications; Fibrin; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Metalloendopeptidases; Plasminogen Activators; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Stroke; Tenecteplase; Thrombolytic Therapy; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

Topics: Anticoagulants; Biomarkers; Coronary Disease; Coronary Vessels; Endothelium, Vascular; Fibrin; Graft Occlusion, Vascular; Heart Transplantation; Humans; Muscle, Smooth, Vascular; Transplantation, Homologous

Imaging with the 99mTc-T2G1s monoclonal antifibrin antibody fragment (Fab') has demonstrated promise in the noninvasive detection of venous thrombi in humans. The purpose of this study was to determine whether chronic arterial thrombi can also be detected by antifibrin antibody imaging.. Eighteen subjects with chronic arterial thrombi were studied with planar and tomographic imaging at 0 to 24 hr postinjection of 99mTc-labeled T2G1s monoclonal antifibrin antibody fragment. Imaging with 111In-labeled platelets was also performed. Images were visually graded by two observers as 0, 1, 2 or 3 (no, faint, moderate or marked) uptake, and quantitative analysis of tomographic images was done in 13 subjects.. On visual analysis of planar images, 44% (8 of 18) of antifibrin patient studies were 1.0 or more and 66% (10 of 18) were judged negative compared with 94% (15 of 16) of platelet patient studies judged 1.0 or more and 6% (1 of 16) judged as negative (p < 0.01). Visual analysis of tomographic images was similar, with 61% (11 of 18) of antifibrin studies graded 1.0 or more compared with 100% (17 of 17) of platelet studies (p < 0.01). The tomographic target-to-background ratio was higher with platelets than with antifibrin antibody (2.5 +/- 1.4 versus 1.8 +/- 1.0, p < 0.05).. In the large-vessel chronic arterial thrombi studied, the results of 99mTc-labeled monoclonal T2G1s antifibrin Fab' imaging were positive in only one-half of the patients studied, significantly less than the findings with platelet imaging, which were positive in all subjects. The higher rate of positive images with labeled platelets than with labeled antifibrin antibodies may be largely due to thrombus age, with continued platelet deposition but little active fibrin deposition.

Topics: Aged; Aortic Aneurysm, Abdominal; Blood Platelets; Chronic Disease; Fibrin; Graft Occlusion, Vascular; Heart Diseases; Humans; Image Processing, Computer-Assisted; Indium Radioisotopes; Male; Radioimmunodetection; Technetium; Thrombosis

To minimize intraoperative blood loss a watertight knitted Dacron aortoiliac prosthesis has been developed by impregnation with bovine collagen. A potential disadvantage is that collagen may be associated with an increase in thrombus formation. We conducted a prospective randomized trial to study the systemic effects of collagen-impregnated prostheses and of aortoiliac operation as such on the coagulation mechanism during the first 10 days after operation. Forty-one patients randomly received either a collagen-impregnated (n = 20) or a nonimpregnated prosthesis (n = 21). Twelve patients who underwent cholecystectomies served as controls. Three markers of the coagulation mechanism were monitored: beta-thromboglobulin, fibrinopeptide A, and fibrin/fibrinogen degradation products. We found no significant differences in median beta-thromboglobulin, fibrinopeptide A, and fibrin/fibrinogen degradation product levels between patients in the collagen-impregnated prosthesis group and patients in the nonimpregnated prosthesis group. This indicates that collagen does not stimulate the coagulation cascade any more than conventional Dacron protheses do. In a comparison of patients who underwent aortoiliac reconstruction and patients who underwent cholecystectomies, the results indicated a significant increased platelet activation and fibrin metabolism in aortoiliac reconstruction group compared with the control group. Finally, we observed a significantly higher preoperative fibrin metabolism in patients with vascular disease than in control subjects. This difference is attributable to the high preoperative fibrin/fibrinogen degradation product values in patients with aortic aneurysms.

Topics: Adult; Aged; Aged, 80 and over; Aorta; Aortic Aneurysm; Arterial Occlusive Diseases; beta-Thromboglobulin; Blood Vessel Prosthesis; Collagen; Female; Femoral Artery; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Graft Occlusion, Vascular; Humans; Iliac Artery; Male; Middle Aged; Platelet Activation; Polyethylene Terephthalates

Outflow graft (OG) obstruction is a dangerous complication that may occur for various reasons after left ventricular assist device (LVAD) implantation.. We describe the case of a 51-year-old patient on LVAD support who developed significant OG kinking and external OG obstruction due to a fibrin mass causing severe stenosis. Both the OG kinking and external obstruction were eliminated via a left lateral thoracotomy.

Topics: Fibrin; Graft Occlusion, Vascular; Heart-Assist Devices; Humans; Male; Middle Aged; Prosthesis Implantation; Thoracotomy; Thrombosis; Treatment Outcome

Hypolysible fibrin clots composed of tightly packed fibers characterize patients with peripheral artery disease (PAD) especially those with critical limb ischemia (CLI). Little is known about the impact of a prothrombotic clot phenotype on restenosis following endovascular revascularization in CLI. The goal of this study was to compare fibrin clot properties and their determinants in CLI patients with restenosis after endovascular treatment (ET) and those free of this complication.. 85 patients with CLI and restenosis within 1 year after ET on optimal pharmacotherapy and 47 PAD control patients without restenosis were included into the study. Plasma fibrin clot permeability (Ks, a measure of the average pore size in the fibrin network) and clot lysis time (CLT) with its potential determinants were determined. During follow-up, the composite endpoint including re-intervention, amputation and death was assessed.. Compared with the control group, patients with restenosis had reduced K. The increased thrombin formation and unfavorable fibrin clot properties occur in patients with CLI who experienced restenosis despite optimal endovascular and pharmacological therapy.

Topics: Aged; Aged, 80 and over; Extremities; Female; Fibrin; Fibrin Clot Lysis Time; Graft Occlusion, Vascular; Humans; Ischemia; Male; Mechanical Thrombolysis; Middle Aged; Peripheral Arterial Disease; Thrombin; Thrombosis

Peri-strut low-intensity area (PLI) is a common imaging finding during the evaluation of in-stent neointima using optical coherence tomography (OCT). We aimed to determine the biological significance of PLI by comparing in-vivo OCT images with the corresponding histological sections obtained from the familial hypercholesterolemic swine model of coronary stenosis.. A total of 26 coronary vessels of nine familial hypercholesterolemic swine were injured with 30% balloon overstretch and then immediately followed by everolimus eluting or bare metal stent placement at 20% overstretch. At 30 days, all stented vessels were subjected to in-vivo OCT analysis and were harvested for histological evaluation. For OCT analysis, stent cross-sections (three per stent) were categorized into presence (PLI+) or absence (PLI-) of PLI. In histology, inflammation and fibrin deposition were scored semiquantitatively from 0 (none) to 3 (severe).. PLI was found in 64.9% of stent sections. Peri-strut inflammation was more frequently observed in OCT sections PLI (+) compared with PLI (-) (56.0 vs. 7.4%, P=0.01). In contrast, peri-strut fibrin deposits was similar in both groups (PLI+=58.0% vs. PLI-=59.3%, P=0.94). Histological neointimal thickness was significantly higher in PLI (+) sections (mean±SE: 0.68±0.06 vs. 0.34±0.02 mm; P<0.01), yielding a higher percent area stenosis compared with PLI (-) (mean±SE: 59.0±4.4 vs. 34.1±2.2%, P<0.01). The PLI diagnostic sensitivity and specificity for inflammation were 80 and 76.1%, respectively (>56% PLI, area under the curve=0.86, P<0.01), whereas for fibrin deposition, the sensitivity and specificity were 42.2 and 76.1%, respectively (area under the curve=0.56, P=NS). Area under the receiver operating characteristic curve was significantly higher for identifying inflammation than fibrin (0.86 vs. 0.56, P<0.01). The severity of PLI correlated with the neointimal thickness when assessed by OCT (R=0.79, P<0.001).. The presence of PLI in OCT correlates with neointimal thickness and appears to have a diagnostic value in the recognition of peri-strut inflammation, therefore possibly serving as a surrogate for in-vivo assessment of stent efficacy.

Topics: Animals; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Fibrin; Graft Occlusion, Vascular; Hyperlipoproteinemia Type II; Hyperplasia; Inflammation; Male; Neointima; Stents; Swine; Tomography, Optical Coherence

To compare the rates of central venous stenosis in patients undergoing hemodialysis who underwent disruption of fibrin sheath with percutaneous transluminal angioplasty balloons and those who underwent over-the-wire catheter exchange. This study is a retrospective review of 209 percutaneous transluminal angioplasty balloon disruption and 1304 over-the-wire catheter exchange procedures performed in 753 patients. Approval from the Human Investigations Committee was obtained for this study. Up to 10-year follow-up was performed. A χ(2) test was used to compare the rates of central venous stenosis after balloon disruption versus catheter exchange. A t-test was used to compare time to central venous stenosis development. Of the 753 patients in the study, 127 patients underwent balloon disruption of fibrin sheath and 626 had catheter exchange. Within the balloon disruption group, 18 (14.2%) of 127 patients subsequently developed central venous stenosis, compared with 44 (7.0%) of 626 in the catheter exchange group (P < 0.01, χ(2) test). Time to central venous stenosis development was approximately 3 years in both groups and not significantly different (1371 and 1010 days, P = 0.20). A total of 25.2% of patients in the balloon disruption group had four or more subsequent catheter exchanges, versus 12.6% in the catheter exchange group (P < 0.01, χ(2) test). In conclusions, there is a possible association between percutaneous transluminal angioplasty balloon disruption of fibrin sheath and late-onset central venous stenosis. Because venography was not routinely performed in catheter exchange patients, future randomized studies are necessary to confirm these findings.

Topics: Angioplasty; Catheterization, Central Venous; Catheters, Indwelling; Chi-Square Distribution; Female; Fibrin; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Radiography, Interventional; Renal Dialysis; Retrospective Studies; Vascular Patency

Coronary late stent thrombosis, a rare but devastating complication, remains an important concern in particular with the increasing use of drug-eluting stents. Notably, pathological studies have indicated that the proportion of uncovered coronary stent struts represents the best morphometric predictor of late stent thrombosis. Intracoronary optical frequency domain imaging (OFDI), a novel second-generation optical coherence tomography (OCT)-derived imaging method, may allow rapid imaging for the detection of coronary stent strut coverage with a markedly higher precision when compared with intravascular ultrasound, due to a microscopic resolution (axial approximately 10-20 microm), and at a substantially increased speed of image acquisition when compared with first-generation time-domain OCT. However, a histological validation of coronary OFDI for the evaluation of stent strut coverage in vivo is urgently needed. Hence, the present study was designed to evaluate the capacity of coronary OFDI by electron (SEM) and light microscopy (LM) analysis to detect and evaluate stent strut coverage in a porcine model.. Twenty stents were implanted into 10 pigs and coronary OFDI was performed after 1, 3, 10, 14, and 28 days. Neointimal thickness as detected by OFDI correlated closely with neointimal thickness as measured by LM (r = 0.90, P < 0.01). The comparison of stent strut coverage as detected by OFDI and SEM analysis revealed an excellent agreement (r = 0.96, P < 0.01). In particular, stents completely covered by OFDI analysis were also completely covered by SEM analysis. All incompletely covered stents by OFDI were also incompletely covered by SEM. Analyses of fibrin-covered stent struts suggested that these may rarely be detected as uncovered stent struts by OFDI. Importantly, optical density measurements revealed a significant difference between fibrin- and neointima-covered coronary stent struts [0.395 (0.35-0.43) vs. 0.53 (0.47-0.57); P < 0.001], suggesting that differences in optical density provide information on the type of stent strut coverage. The sensitivity and specificity for detection of fibrin vs. neointimal coverage was evaluated using receiver-operating characteristic analysis.. The present study demonstrates that OFDI is a highly promising tool for accurate evaluation of coronary stent strut coverage, as supported by a high agreement between OFDI and light and electron microscopic analysis. Furthermore, our data indicate that optical density measurements can provide additional information with respect to the type of stent strut coverage, i.e. fibrin vs. neointimal coverage. Therefore, coronary OFDI analysis will provide important information on the biocompatibility of coronary stents.

Topics: Animals; Coronary Vessels; Fibrin; Graft Occlusion, Vascular; Microscopy; Microscopy, Electron, Scanning; Prosthesis Failure; ROC Curve; Stents; Swine; Tomography, Optical Coherence; Wound Healing

The extracellular matrix protein osteopontin (OPN) plays a nonredundant role in atherosclerosis and restenosis. Here we investigated the impact of OPN up-regulation in an in vitro model of re-endothelialization after mechanical injury of the endothelial cell monolayer. Murine aortic endothelial (MAE) cells interact via alpha(v) integrins with the integrin-binding Arg-Gly-Asp OPN sequence and adhere to immobilized OPN. On this basis, MAE cells were stably transfected with a wild-type OPN cDNA (OPN-MAE cells), with an OPN mutant lacking the Arg-Gly-Asp sequence (DeltaRGD-OPN-MAE cells), or with vector alone (mock-MAE cells). When compared with mock-MAE and DeltaRGD-OPN-MAE cells, OPN-MAE cells showed a reduced sprouting activity in fibrin gel, a reduced motility in a Boyden chamber assay, and a reduced capacity to repair the wounded monolayer. Accordingly, OPN-MAE cells at the edge of the wound were unable to form membrane ruffles, to reorganize their cytoskeleton, and to activate the focal adhesion kinase and the small GTPase Rac1, key regulators of the cell entry into the first phase of the cell migration cycle. Accordingly, wounded OPN-MAE cells failed to activate the intracellular signals RhoA and ERK1/2, involved in the later phases of the cell migration cycle. Also, parental MAE cells showed reduced re-endothelialization after wounding when seeded on immobilized OPN and exhibited increased adhesiveness to OPN-enriched extracellular matrix. In conclusion, OPN up-regulation impairs re-endothelialization by inhibiting the first phase of the cell migration cycle via alpha(v) integrin engagement by the extracellular matrix-immobilized protein. This may contribute to the adverse effects exerted by OPN in restenosis and atherosclerosis.

Topics: Animals; Aorta; Atherosclerosis; Cell Line, Transformed; Cell Movement; Endothelial Cells; Extracellular Matrix; Fibrin; Focal Adhesion Protein-Tyrosine Kinases; Graft Occlusion, Vascular; Integrin alphaV; MAP Kinase Signaling System; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mutation; Neuropeptides; Osteopontin; rac GTP-Binding Proteins; rac1 GTP-Binding Protein; Recombinant Proteins; Transfection

Intimal hyperplasia and surface thrombogenicity are major factors in the high failure rate of synthetic small-diameter bypass grafts. Vascular endothelial growth factor is a potent stimulus for endothelial growth, and its provision in a fibrin matrix coating at the luminal graft surface may hold a key to spontaneous graft endothelialization and improved graft patency.. Pigs underwent bilateral carotid artery interposition of expanded polytetrafluoroethylene grafts either impregnated with fibrin (n = 11)--engineered to locally release vascular endothelial growth factor121 (vascular endothelial growth factor-fibrin; n = 11)--or left uncoated (n = 12). Graft patency was assessed by quantitative carotid angiography followed by graft histomorphometry at the 1-month experimental end point.. Patency rates were not significantly different between study groups. Grafts coated with fibrin or vascular endothelial growth factor-fibrin exhibited significantly increased angiographic narrowing at the proximal anastomosis (for both P < .05 vs uncoated) and no difference at the distal anastomosis and the grafts' middle. Histological analysis showed 80% to 90% endothelial coverage and buildup of intima throughout the lengths of all grafts. Examination of the grafts' midportion revealed significantly enlarged neointimal layers of smooth muscle actin-positive cells in grafts coated with vascular endothelial growth factor-fibrin (242 +/- 47 microm2/micron) and fibrin (177 +/- 41 microm2/micron), compared with uncoated grafts (131 +/- 39 microm2/micron) (for both P < .05 vs uncoated). This thickening could not be explained by enhanced inflammation or vessel wall angiogenesis, which were minimal at the experimental end point.. Fibrin and vascular endothelial growth factor produced effects deleterious to graft healing, by increasing the narrowing at proximal anastomosis and neointimal growth beyond that seen in uncoated grafts. It may reflect direct activation by exogenous vascular endothelial growth factor of vascular smooth muscle cells.

Topics: Animals; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Capillaries; Carotid Arteries; Coated Materials, Biocompatible; Fibrin; Graft Occlusion, Vascular; Immunohistochemistry; Macrophages; Polytetrafluoroethylene; Sus scrofa; Tunica Intima; Vascular Endothelial Growth Factor A; Vascular Patency

We studied whether there was a relationship between the anticoagulant effects of recombinant human soluble thrombomodulin (rhsTM) and activation of protein C in a primate model of acute vascular graft thrombosis in 11 baboons (Papio species). Baboons were pretreated with 0.1, 1 and 5 mg/kg of rhsTM, with or without co-injection of a neutralising monoclonal antibody to protein C (HPC4) in the 1 mg/kg rhsTM group. Subsequently, thrombogenic polyester grafts were deployed for 3 h into chronic exteriorised arteriovenous shunts. Thrombus growth in the graft, plasma-activated protein C (APC) levels, coagulation and thrombosis markers were determined. In untreated baboons, baseline circulating APC levels more than doubled and graft thrombi propagated until reaching equilibrium in about 1 h. Treatment with rhsTM reduced thrombus propagation rates, prolonged the clotting and bleeding times, decreased thrombin-antithrombin complex, beta-thromboglobulin and fibrinopeptide A levels, and, surprisingly, also decreased systemic APC levels, in a dose-dependent manner. In the presence of HPC4 antibody to inhibit APC generation, the acute antithrombotic activity of rhsTM on graft thromboses was not attenuated for up to 80 min, but sustained thrombus accumulation was observed over a 180-min period. These findings suggest that, in contrast to the prevailing hypotheses, the primary antithrombotic activity of rhsTM is independent of protein C, at least in this primate model. Direct inhibition of thrombin's prothrombotic activity upon complex formation with rhsTM might explain the molecular mechanism of the observed antithrombotic effect.

Topics: Animals; Antibodies, Monoclonal; Anticoagulants; Antithrombin III; Blood Coagulation; Blood Platelets; Dose-Response Relationship, Drug; Fibrin; Graft Occlusion, Vascular; Male; Papio; Partial Thromboplastin Time; Peptide Hydrolases; Protein C; Recombinant Proteins; Solubility; Thrombomodulin; Thrombosis

To compare median patency times after treatment of malfunctioning tunneled hemodialysis catheters by one of three techniques: over-the-wire catheter exchange (CE), fibrin sheath stripping (FSS) from a femoral vein approach, and over-the-wire catheter removal with balloon dilation of fibrin sheath (DFS) followed by catheter replacement with use of the same tract.. Retrospective study was conducted of 66 consecutive procedures performed over a period of 47 months for poor flow through tunneled hemodialysis catheters despite tissue plasminogen activator infusion trials (CE, n=33; FSS, n=18; DFS, n=15). Baseline parameters (time since initial catheter placement, number of previous catheter interventions, catheter access site, and patient age and sex) were recorded to identify possible pretreatment differences among groups. Outcome comparison was based on duration of adequate catheter function on dialysis during follow-up.. No significant differences in baseline parameters were identified among the three groups (P>.05). Mean follow-up duration (67+/-89 days; range, 0-398 d) was similar among the three groups. The immediate technical success rate was 100%, and there were no complications. Cumulative catheter patency rates were 73% (CE), 72% (FSS), and 65% (DFS) at 1 month; 43% (CE), 60% (FSS), and 39% (DFS) at 3 months; and 28% (CE), 45% (FSS), and 39% (DFS) at 6 months. Median duration of patency was similar among groups (P=.60).. All three therapies were equivalent in terms of immediate technical success, complication rates, and durability of catheter function during later follow-up. Hence, when one technique is chosen over another, factors other than the period of secondary patency should be considered, such as cost and patient and physician preference.

Topics: Adult; Aged; Aged, 80 and over; Catheterization; Catheterization, Central Venous; Catheters, Indwelling; Equipment Failure; Female; Femoral Vein; Fibrin; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Postoperative Complications; Radiography, Interventional; Renal Dialysis; Retrospective Studies; Tissue Plasminogen Activator; Treatment Outcome; Vascular Patency

Restenosis is a major health care problem, with approximately 40% of angioplasties resulting in restenosis. Mechanisms related to elastic recoil, cell proliferation, and extracellular matrix (ECM) synthesis are implicated. In vivo studies have demonstrated the potential for cryotherapy to combat the process of restenosis, but the mechanisms whereby freezing and/or cooling can reduce or eliminate smooth muscle cell (SMC) proliferation and ECM synthesis are not well known. While in vivo testing is ultimately necessary, in vitro models can provide important information on thermal parameters and mechanisms of injury. However, it is important to carefully choose the model system for in vitro work on cryoinjury characterization to adequately reflect the clinical situation. In this study, we examined the differences in response to cryoinjury by SMCs from different species (rat, pig, and human) and in different cellular environments (suspension vs. tissue equivalent). Tissue equivalents, composed of cells embedded in collagen or fibrin gel, provide a 3-D tissue-like environment, while allowing for controlled composition. As reported here, all SMCs showed similar trends, but rat cells appeared less sensitive to cooling at faster cooling rates in suspension, while human SMCs were less sensitive to temperatures just above freezing when embedded in collagen. In addition, the SMCs were less sensitive in suspension than they were in collagen. Cells in suspension exhibited 70% viability at -11 degrees C, whereas cells in the tissue equivalent model showed only 30% survival. Future studies will aim to more adequately represent the conditions in restenosis by providing inflammatory and proliferative cues to the cells.

Topics: Angioplasty; Animals; Cell Survival; Cryotherapy; Fibrin; Graft Occlusion, Vascular; Humans; In Vitro Techniques; Models, Biological; Muscle, Smooth, Vascular; Rats; Species Specificity; Swine

There is an urgent need to treat restenosis, a major complication of the treatment of arteries blocked by atherosclerotic plaque, using local delivery techniques. We observed that cross-linked fibrin (XLF) is deposited at the site of surgical injury of arteries. An antibody to XLF, conjugated to anti-restenotic agents, should deliver the drugs directly and only to the site of injury. An anti-XLF antibody (H93.7C.1D2/48; 1D2) was conjugated to heparin (using N-succinimidyl 3-(2-pyridyldithio)propionate), low molecular weight heparin (LMWH) (adipic acid dihydrazide) and rapamycin (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide), and the conjugates purified and tested for activity before use in vivo. Rabbits had their right carotid arteries de-endothelialised and then given a bolus of 1D2-heparin, 1D2-LMWH or 1D2-rapamycin conjugate or controls of saline, heparin, LMWH, rapamycin or 1D2 (+/-heparin bolus) and sacrificed after 2 or 4 weeks (12 groups, n=6/group). Rabbits given any of the conjugates had minimal neointimal development in injured arteries, with up to 59% fewer neointimal cells than those given control drugs. Rabbits given 1D2-heparin or 1D2-LMWH had an increased or insignificant reduction in luminal area, with positive remodelling, while the medial and total arterial areas of rabbits given 1D2-rapamycin were not affected by injury. Arteries exposed to 1D2-heparin or 1D2-rapamycin had more endothelial cells than rabbits given control drugs. Thus, XLF-antibodies can site-deliver anti-restenotic agents to injured areas of the artery wall, where the conjugates can influence remodelling, re-endothelialisation and neointimal cell density, with reduced neointimal formation.

Topics: Animals; Anti-Bacterial Agents; Antibodies; Cell Count; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Cross-Linking Reagents; Drug Delivery Systems; Electrophoresis, Polyacrylamide Gel; Fibrin; Graft Occlusion, Vascular; Heparin; Heparin, Low-Molecular-Weight; Rabbits; Sirolimus; Succinimides

The autogenous vein represents the graft material of choice in crural and pedal bypass surgery. Because of the numerous problems concerning the graft harvesting and the quality of autogenous vein material an equally good allogenous graft is urgently needed. Up to the present times no such graft material has been able to achieve the success of vein grafts.. We investigated the knitted polyester prosthesis Terumo PF-V (Terumo Comp., Japan), diameter 5 mm with outer reinforce, which is characterized by a new coating of plasmin-treated fibrin. Grafts were implanted as bypass into the ligated carotid (n = 10) and femoral arteries (n = 10) of 10 dogs (beagles). As a control 5 mm-ePTFE-prostheses (Impra Carboflo) were implanted simultaneously on the contralateral side.. After 6 months, seven of 20 PF-V-grafts and 8 of 20 PTFE-grafts were patent. All prostheses presented with good macroscopic healing characteristics. In the patent grafts, angiography showed no substantial stenoses. The histological examination of the material was performed using light microscopy, transmission polarising microscopy, scanning electron microscopy, and transmission electron microscopy. Both types of prostheses showed the typical pattern of graft healing by migration of mesenchymal cells through the prosthesis, formation of capillaries, and growing of a neointima with endothelium-like cells. All failed bypass grafts presented with an occluding proliferation from the arterial wall into the anastomotic region.. Using clinically or histologically evaluation, neither graft demonstrated superiority over the other. The results indicate that the coating plays only a minor role for graft healing if any. For proper graft function, the arterial wall proliferation at the anastomotic region, which is not dependent on the type of prosthesis, appears to be most important. The overall results concerning both types of prostheses were disappointing.

Topics: Animals; Blood Vessel Prosthesis; Carotid Arteries; Coated Materials, Biocompatible; Dogs; Femoral Artery; Fibrin; Fibrinolysin; Graft Occlusion, Vascular; Polyesters; Polytetrafluoroethylene; Prosthesis Design; Wound Healing

The authors assess a new ePTFE-nitinol stent for its long-term patency, healing, and properties of endothelialization.. Adult greyhounds (n = 18) underwent bilateral iliofemoral placement of an endoprosthesis (Hemobahn) consisting of a nitinol stent lined with an ultrathin expanded polytetrafluoroethylene (ePTFE) material. Histologic and quantitative morphometric analyses were performed on devices explanted at 2 weeks and 1, 3, 6, and 12 months. The source of endothelialization was examined in four additional devices modified by sealing either the proximal and distal ends or the entire graft with poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP), a nonporous laminate to prevent potential transgraft endothelial cell migration.. Device patency assessed with both intravascular ultrasound and histologic study showed minimal arterial stenosis, irrespective of implant duration. The neointima at less than 3 months consisted of fibrin and inflammatory infiltrate; at later time points, it was composed of mostly smooth muscle cells. Flow surfaces were more than 75% endothelialized by 3 months, which was nearly complete by 6 months. Modified endoprostheses entirely enveloped with FEP resulted in endothelialization of only the proximal and distal ends; the middle regions showed nonocclusive thrombi. Conversely, devices wrapped proximally and distally showed nearly complete endothelialization.. This ePTFE-nitinol endoprosthesis demonstrated long-term patency at up to 1 year after implantation and showed early and nearly complete endothelialization by 6 months. The design promoted rapid endothelialization of flow surfaces, particularly in the midregion of the device possibly by transgraft migration.

Topics: Alloys; Animals; Blood Vessel Prosthesis; Cell Movement; Dogs; Endothelium, Vascular; Female; Femoral Artery; Fibrin; Follow-Up Studies; Graft Occlusion, Vascular; Hemorheology; Iliac Artery; Image Processing, Computer-Assisted; Male; Microscopy, Electron, Scanning; Muscle, Smooth, Vascular; Polytetrafluoroethylene; Prosthesis Design; Stents; Surface Properties; Tunica Intima; Ultrasonography, Interventional; Vascular Patency; Wound Healing

The effect on graft thrombogenicity of binding heparin to the luminal surface of prosthetic arterial grafts was investigated. Venous blood was obtained from healthy volunteers and exposed for 30 minutes to tubular segments of standard knitted dacron, polytetrafluoroethylene (PTFE) and a recently introduced heparin-bound knitted dacron graft. After this exposure the fibrinogen level of each sample was measured. The median (range) fibrinogen levels (expressed as a percentage of that in unexposed blood samples) were: standard dacron 3.5% (0-5.4%); PTFE 95.5% (0-121.1%); and heparin-bound dacron 79.8% (3.8-109.6%). Fibrinogen levels in the standard dacron group were significantly less than that of the PTFE and heparin-bound dacron groups (P < 0.05). No significant difference was found between the fibrinogen levels of the PTFE and heparin-bound dacron groups (P = 0.35). These findings suggest that heparin binding significantly reduces fibrinogen consumption and hence may reduce graft thrombogenicity.

Topics: Anticoagulants; Arteries; Biocompatible Materials; Blood Coagulation; Blood Vessel Prosthesis; Equipment Failure; Evaluation Studies as Topic; Fibrin; Fibrinogen; Graft Occlusion, Vascular; Heparin; Humans; In Vitro Techniques; Materials Testing; Microscopy, Electron, Scanning; Polyethylene Terephthalates; Polytetrafluoroethylene; Reference Values; Surface Properties; Thrombosis

To determine whether fibrin deposition during the first month following cardiac transplantation predicts development of coronary artery disease and graft failure in cardiac allograft recipients.. We prospectively studied 121 consecutive adult patients who received cardiac transplants between 1988 and 1995. Serial endomyocardial biopsies obtained during the first month posttransplant (2.3 + 0.6 biopsies/patient) were studied immunohistochemically for fibrin deposits. Patients were followed up with annual angiograms (3.2 + 1.7/patient) evaluated with side-by-side comparisons for the presence and progression of coronary artery disease.. All pretransplant biopsies were fibrin-negative; 60 allografts (50%) remained without fibrin, and 61 (50%) contained fibrin during the first posttransplant month. Of allografts with fibrin, 72% developed coronary artery disease, while 27% of allografts without fibrin developed the disease (P <0.001). Coronary artery disease was progressive in 61% of allografts with fibrin, and in 25% of allografts without fibrin (P <0.001). Graft failure was more frequent and time-to-graft-failure occurred earlier in patients whose allografts had fibrin during the first month after transplantation (P <0.001).. Fibrin in biopsies during the first month after transplantation identifies patients at high risk for developing coronary artery disease or graft failure, thereby allowing the opportunity to initiate preventive procedures.

Topics: Adult; Biopsy; Coronary Angiography; Coronary Disease; Diagnosis, Differential; Female; Fibrin; Graft Occlusion, Vascular; Heart Transplantation; Humans; Male; Middle Aged; Myocardium; Risk; Time Factors

We evaluated the contributions of coagulation factors IIa (thrombin) and Xa to small-diameter prosthetic graft thrombogenicity in vivo.. Preclotted and nonpreclotted (collagen-coated) polyester grafts were studied before and 24 hours after implantation into pig femoral arteries. After incubation of explanted grafts was performed with plasma depleted of vitamin K-dependent coagulation factors by barium chloride adsorption (Ba-plasma), graft-associated thrombin activity was determined by radioimmunoassay for fibrinopeptide A. Fibrinopeptide A levels reflect thrombin-mediated fibrin formation. Factor Xa activity was characterized by measuring activation of prothrombin added to Ba-plasma.. Thrombin and factor Xa were associated with the luminal surfaces of preclotted grafts before and 24 hours after implantation. Nonpreclotted grafts had negligible procoagulant activity before implantation. After 24 hours in vivo graft-associated factor Xa activity was similar in both nonpreclotted and preclotted grafts; however, more thrombin was bound to nonpreclotted coated grafts (p < 0.01).. The procoagulant activity of small-diameter prosthetic grafts persists for 24 hours after implantation and is attributable not only to graft-associated thrombin but also to de novo thrombin elaboration induced by factor Xa. Moreover, graft-associated procoagulant activity is not dependent on preclotting because it develops on nonpreclotted, collagen-coated grafts as well. Treatment strategies to attenuate graft thrombosis may require the inhibition of both thrombin and factor Xa.

Topics: Adsorption; Animals; Barium Compounds; Blood Coagulation; Blood Vessel Prosthesis; Chlorides; Collagen; Factor Xa; Femoral Artery; Fibrin; Fibrinopeptide A; Graft Occlusion, Vascular; Polyesters; Polyethylene Terephthalates; Prosthesis Design; Prothrombin; Surface Properties; Swine; Thrombin; Thrombosis; Vitamin K

Platelet accumulation on small- and medium-calibre vascular grafts plays a significant role in graft occlusion. We examined platelet accumulation on the surface of fibrin-coated polyethylene tubing (internal diameter 0.17 cm) during 10 min flow (10 ml/min) at high wall shear rate (764 s-1). Washed platelets labelled with 51Cr were resuspended in Tyrode solution containing albumin, apyrase and red blood cells (hematocrit 40%). When the thrombin that was used to form the fibrin-coated surface was inactivated with FPRCH2Cl before perfusion of the tubes with the platelet: red blood cell suspension, the accumulation of platelets was 59,840 +/- 27,960 platelets per mm2, whereas accumulation on fibrin with residual active thrombin was 316,750 +/- 32,560 platelets per mm2 (n = 4). When the fibrin on the surface was cross-linked by including recombinant factor XIII (rFXIII) in the fibrinogen solution used to prepare the fibrin-coated surface, platelet accumulation, after thrombin neutralization, was reduced by the cross-linking from 46,974 +/- 9702 to 36,818 +/- 7964 platelets per mm2 (n = 12, p < 0.01). Platelet accumulation on tubes coated with D-dimer was ten times less than on tubes coated with D-domain; this finding also supports the observation that cross-linking of fibrin with the formation gamma-gamma dimers reduces platelet accumulation on the fibrin-coated surface. Thrombin-activated platelets themselves were shown to cross-link fibrin when they had adhered to it during perfusion, or in a static system in which thrombin was used to form clots from FXIII-free fibrinogen in the presence of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Factor XIII; Fibrin; Fibrin Fibrinogen Degradation Products; Graft Occlusion, Vascular; Humans; Microscopy, Electron, Scanning; Molecular Sequence Data; Platelet Activation; Platelet Adhesiveness; Polyethylenes

We present an novel approach to in vivo testing of vascular grafts. Seven grafts of two different materials, each with an inner diameter of 5 mm, were joined together to form a bundle, the ends of which were joined to connecting segments with an inner diameter of about 15 mm. The device was then implanted into the abdominal aorta of an experimental animal. After surgery, the animal was followed by CT scan at regular intervals to assess patency of each individual graft. The model features an increased number of grafts per animal with standardized anastomoses and hemodynamic conditions, but it needs modification to lower its thrombogenic potential.

Topics: Anastomosis, Surgical; Animals; Blood Vessel Prosthesis; Cattle; Connective Tissue; Female; Fibrin; Graft Occlusion, Vascular; Male; Polytetrafluoroethylene; Prosthesis Design; Prosthesis Failure; Sheep

The healing characteristics of polymer-coated Dacron grafts with or without heparin-bonding and collagen-coated Dacron grafts are compared with standard knitted Dacron grafts by implanting eight of each graft into pig iliac arteries. The grafts were implanted at random bilaterally with end-to-side anastomoses. The grafts were explanted after 1, 2 and 4 weeks and prepared for histological evaluation by in vivo fixation. Graft segments were investigated by light microscopy, scanning electron microscopy and transmission electron microscopy. The endothelial coverage, intimal thickness and healing characteristics were subjected to one-way analysis of variance. One week after surgery endothelial-like cells appeared close to the anastomoses and after 2 weeks a clear growing endothelial edge was observed in the collagen-coated grafts. After 4 weeks' implantation all grafts were patent and endothelial cells covered the grafts to a various extent. Collagen-coated grafts had significantly greater endothelial cell coverage compared with Dacron and polymer-coated grafts without heparin bonding (P < 0.05). Evaluation by transmission electron microscopy revealed the luminal coverage of the collagen-coated grafts to consist of organized smooth muscle cells and endothelial cells containing Weibel-Palade bodies. The smooth muscle cells in the other grafts were less organized and were covered by endothelial cells to a lesser degree. No differences were noted regarding the inflammatory response of the graft materials and no further positive effects were encountered by the addition of heparin to the polymer coating. The study demonstrates that various coating procedures and surface modulation of knitted Dacron grafts produce a graft which is impervious to blood but still allows tissue incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anastomosis, Surgical; Animals; Aorta, Abdominal; Blood Vessel Prosthesis; Collagen; Endothelium, Vascular; Fibrin; Graft Occlusion, Vascular; Heparin; Iliac Artery; Neutrophils; Polyethylene Terephthalates; Polymers; Prosthesis Design; Quaternary Ammonium Compounds; Surface Properties; Swine; Thrombosis; Vascular Patency; Wound Healing

The effect of endothelial cell seeding on the patency of small-caliber expanded polytetrafluoroethylene (ePTFE) grafts used for venous replacements in a canine experimental model was evaluated. Grafts were implanted bilaterally in 12 dogs as femoral vein interpositions. In each animal, one graft was seeded with enzymatically derived homologous endothelial cells which had been cultivated for 3 days in vitro before implantation, whereas the contralateral graft was not seeded. In five dogs, venography was performed at 2 weeks, and grafts were then excised. In the remaining seven dogs, venography was performed at both 2 and 4 weeks, with graft excision at 4 weeks. Graft patency at 2 weeks for seeded grafts was 75% (nine of 12) compared with only 33% (four of 12) for unseeded grafts (P < 0.02). There were no new episodes of thrombotic occlusion between 2 and 4 weeks. Five dogs with thrombus in the control graft did not develop thrombus in the contralateral seeded graft. Furthermore, each dog with a patent control graft had no thrombus in the seeded graft. It is concluded that the early patency of seeded ePTFE grafts is superior to that of unseeded ePTFE grafts in the femoral vein.

Topics: Animals; Blood Vessel Prosthesis; Cells, Cultured; Dogs; Endothelium, Vascular; Female; Femoral Vein; Fibrin; Fibrinolysis; Graft Occlusion, Vascular; Platelet Aggregation; Polytetrafluoroethylene; Surface Properties

To study blood compatibility of venous prosthesis made of textile or non-textile material, the inferior vena cava of 37 rabbits was partly replaced by 3 mm internal diameter synthetic tube graft made of textile material (T: woven tetron) or non-textile material (P: polytetrafluoroethylene). At designated time intervals after the replacement (5 hours to 4 weeks), graft patency was examined and the dry weight of intraluminal deposits was measured. The harvested grafts were then subjected to light and scanning electron microscopy. All the T-grafts were occluded as early as 5 hours after grafting but when ticlopidine was administered prior to the grafting, all the grafts were patent. All the P-grafts were patent up to 4 weeks after grafting, though the amount of intraluminal deposits was increased in a time related manner, narrowing the lumen of the grafts. The luminal surface of the P-grafts harvested at 5 hours after grafting was covered by piles of fibrin networks entrapping erythrocytes without an association of platelet aggregates, which resembles the finding in the T-grafts harvested from the ticlopidine treated rabbits. In the P-grafts, both the proximal and distal luminal surfaces near the anastomosis were fully covered with endothelial cells by 2 weeks and the entire luminal surface was covered with these cells by 4 weeks. From these results, the following conclusions were obtained; (1) P-graft was superior to T-graft for venous prosthesis, which is mainly due to the inertness of P against platelet activation. (2) Though the luminal surface of the P-grafts was completely covered with endothelial cells by 4 weeks after grafting, the lumen was markedly narrowed by intimal hyperplasia.

Topics: Animals; Biocompatible Materials; Blood Vessel Prosthesis; Endothelium, Vascular; Erythrocytes; Fibrin; Graft Occlusion, Vascular; Male; Microscopy, Electron, Scanning; Platelet Activation; Polyethylene Terephthalates; Polytetrafluoroethylene; Rabbits; Thrombophlebitis; Ticlopidine; Vena Cava, Inferior

The distribution of re-endothelialization and the development of intimal thickening were investigated electron microscopically and immunohistochemically using saphenous vein grafts implanted into the femoral artery in dogs. Animals were divided into two groups according to a difference of preparation of the venous grafts before implantation: group 1 without storage, and group 2 with storage for 1 h in 0.9% sodium chloride solution containing papaverine and heparin. In group 2 endothelial cells were almost totally denuded at 1 day, while endothelial islands were always left on the back of valves. In group 1 small islands of surviving endothelial cells were occasionally observed away from the valves. By 1 week, the re-endothelialization of group 1 and group 2 extended to 71 +/- 14.7% and 47 +/- 9% (mean +/- SD) of the total luminal surface area, respectively, and spread mainly from the valves but not from the adjacent artery. Immunohistochemical study using anti-dog fibrinogen IgG suggested that increased permeability of the graft wall continued for one month, in spite of the endothelial covering. Intimal thickening was most pronounced at 1 month, especially near the anastomosis, but was less in the middle of the grafts. These results indicate that intimal thickening of the venous grafts is a response to injury which intimately depends on the rate of re-endothelialization.

Topics: Animals; Dogs; Endothelium, Vascular; Fibrin; Fibrinogen; Graft Occlusion, Vascular; Immunoglobulin G; Immunohistochemistry; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Veins

A histopathological study was performed on 36 patients (60 grafts) who had undergone aorto-coronary bypass graft (ACBG) surgery 0 to 99 months prior to death. The following pathologic changes were found: 1) The thickness of diffuse intimal proliferation in the ACBG progressed with time from graft surgery to death. 2) The media became atrophic and the adventitia was increased slightly in thickness. 3) Fibrin deposits were found in 20 patients on/in the intimal thickenings of the vein graft walls and 7 patients showed incorporated fibrin in the thickened intima even one month after surgery. 4) Atherosclerosis, identified as intimal foam cell accumulation or frank plaques, was seen in only 3 patients 4 years after surgery. Fibrointimal proliferation occurred with relatively greater frequency in patients with fibrin deposits (P less than 0.001). Although it is well known that mural thrombi in vein grafts manifest fibrointimal proliferation, our results suggest that fibrin deposits might be responsible for intimal thickening even one month after graft surgery.

Topics: Aged; Autopsy; Coronary Artery Bypass; Coronary Artery Disease; Female; Fibrin; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Myocardium; Retrospective Studies; Saphenous Vein

29 autogenous vein grafts, from 26 patients with peripheral arterial disease, were studied. 4 grafts of Group I (less than 3 months duration) were patent and removed for reasons other than graft failure. These showed 'arterialisation' only; 4 grafts of Group II (duration 5-18 months) showed thrombotic occlusion; 21 grafts of Group III (duration greater than 2 years) showed impaired graft patency and lipid identifiable as apolipoprotein B-containing-lipoproteins (LpB), and fibrinogen-related antigens (FRA) were seen as intramural deposits in the thickened grafts. LpB was also seen in a perifibrous distribution on the collagen of organised thrombi. Complicated lesions in some Group III grafts showed stenosis or occlusion, ulceration, calcification or aneurysm formation. These features suggest that a process indistinguishable from 'true' atherosclerosis affects vein grafts of long duration. The ways in which such changes may: contribute to graft failure; and improve our understanding of the basic processes involved in atherogenesis, are discussed.

Topics: Adult; Aged; Apolipoproteins B; Arteries; Arteriosclerosis; Endothelium; Female; Fibrin; Graft Occlusion, Vascular; Histocytochemistry; Humans; Lipid Metabolism; Male; Middle Aged; Time Factors; Vascular Diseases; Veins

This study was undertaken to analyse the distribution pattern of blood elements deposits in 15 cases of vascular prostheses submitted, ex vivo, to reduced blood flow in a canine model. Autologous blood platelets labeled with Indium-111 and human 125 Iodinated fibrinogen were injected into the animals. Ten minutes later, the blood flow in the aorta was reduced to 50 ml/min and the prostheses (Woven DeBakey, 30 cm long and 6 mm internal diameter), were implanted as substitutes for the infrarenal abdominal aorta. The blood flow was then reestablished to 50 ml/min and controlled throughout the entire experiment. When a thrombosis occurred, or after 4 hours of low blood circulation, the prosthesis was collected, weighted and chemically fixed, and the radioactivity was measured by means of a two-channel gamma scintillation counter. These data were then formatted and processed by a special computer program. Final values were processed for graphical representation and analysed statistically. Results show a lack of correlation between weight of thrombotic matrix, platelet accumulation, and fibrin deposits retained from one animal to the other. There is, though, an appearance of a complex interrelationship between the mean pattern of longitudinal distribution of these elements, which shall be qualified as contagious distal accumulation of the deposits. The influence of each animals' blood characteristics, as evaluated by means of regression analysis, account for 40 to 60% of the interindividual variance in blood deposits. Data corrections following evidence of undesirable influences due to uncontrolled parameters are presented. This experimental method permits simultaneous graphical representation of the distribution of several elements in the thrombotic matrix, and at the same time an elaborate numerical analysis of their longitudinal distribution and total accumulation. The method is easy to use, does not require sophisticated equipment, and is less expensive than scintigraphy.

Topics: Animals; Aorta, Abdominal; Blood Platelets; Blood Vessel Prosthesis; Computers; Dogs; Fibrin; Fibrinogen; Graft Occlusion, Vascular; Indium; Iodine Radioisotopes; Platelet Aggregation; Radioisotopes; Regional Blood Flow; Thrombosis; Time Factors

Microvascular fibrous polyurethane prostheses (inner diameter 1.5 mm, length 10 cm) were implanted in the abdominal aorta of rats. The prostheses were fixed in a loop. All rats (n = 37) were reoperated 6 weeks after implantation to verify the patency of the prostheses. Eight prostheses were obliterated from various causes. The remaining 29 prostheses were found to be patent 3 months after implantation, which gives a patency rate of 79%. Six weeks and 3 months after implantation 7 and 4 rats, respectively, with patent prostheses were sacrificed. The remaining 18 rats of this study are still alive, more than 4 months after implantation, and will be included in long-term observation studies. The prostheses were examined using both light and scanning electron microscopy. The patent prostheses exhibited macroscopically a clear and transparent inner surface. No obliterative processes could be found either macroscopically or microscopically. Neo-intima ingrowth had advanced +/- 10 mm into the prostheses over the anastomotic line from both ends 3 months after implantation, and was continued by a single endothelium layer for several centimeters. An acellular, stable fibrin film was found inbetween the cellular lining. The neo-intima was anchored at the prosthesis by cellular protrusions extending between the polyurethane fibers. Though 10 cm long prostheses were implanted under unfavorable hemodynamic conditions, a patency rate of 79% was achieved, both 6 weeks and 3 months after implantation. This patency rate could have been higher if evident technical failures had been avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aorta, Abdominal; Blood Vessel Prosthesis; Endothelium; Fibrin; Graft Occlusion, Vascular; Hemodynamics; Male; Microcirculation; Microscopy, Electron, Scanning; Polyurethanes; Rats; Rats, Inbred Strains; Rheology