Simulated surface-induced thrombin generation in a flow field.

A computational model of blood coagulation is presented with particular emphasis on the regulatory effects of blood flow, spatial distribution of tissue factor (TF), and the importance of the thrombomodulin-activated protein C inhibitory pathway. We define an effective prothrombotic zone that extends well beyond the dimensions of injury. The size of this zone is dependent on the concentrations of all reactive species, the dimensions of TF expression, the densities of surface molecules, and the characteristics of the flow field. In the case of tandem sites of TF, the relationship between the magnitude of the effective prothrombotic zone and the interval distance between TF sites dictate the net response of the system. Multiple TF sites, which individually failed to activate the coagulation pathway, are shown to interact in an additive manner to yield a prothrombotic system. Furthermore, activation of the thrombomodulin-activated protein C pathway in the regions between sites of TF downregulate the thrombin response at subsequent TF sites. The implications of prothrombotic effects, which extend downstream beyond the discrete site of injury to interact with subsequent lesions are critical given the systemic nature of atherosclerotic disease.

Thrombomodulin improves early outcomes after intraportal islet transplantation.

Primary islet nonfunction due to an instant blood mediated inflammatory reaction (IBMIR) leads to an increase in donor islet mass required to achieve euglycemia. In the presence of thrombin, thrombomodulin generates activated protein C (APC), which limits procoagulant and proinflammatory responses. In this study, we postulated that liposomal formulations of thrombomodulin (lipo-TM), due to its propensity for preferential uptake in the liver, would enhance intraportal engraftment of allogeneic islets by inhibiting the IBMIR. Diabetic C57BL/6J mice underwent intraportal transplantation with B10.BR murine islets. In the absence of treatment, conversion to euglycemia was observed among 29% of mice receiving 250 allo-islets. In contrast, a single infusion of lipo-TM led to euglycemia in 83% of recipients (p = 0.0019). Fibrin deposition (p < 0.0001), neutrophil infiltration (p < 0.0001), as well as expression TNF-alpha and IL-beta (p < 0.03) were significantly reduced. Significantly, thrombotic responses mediated by human islets in contact with human blood were also reduced by this approach. Lipo-TM improves the engraftment of allogeneic islets through a reduction in local thrombotic and inflammatory processes. As an enzyme-based pharmacotherapeutic, this strategy offers the potential for local generation of APC at the site of islet infusion, during the initial period of elevated thrombin production.

A membrane-mimetic barrier for islet encapsulation.

BACKGROUND: Enhanced control of both transport properties and surface physiochemical characteristics will be important steps in the development of an effective immunoisolation barrier critical to the success of pancreatic islet cell transplantation. We hypothesize that the cell membrane establishes an important paradigm for the design of a biomimetic immunoisolation barrier with improved performance characteristics because of its capacity to control interfacial mass transport, as well as its ability to act as a template for more complex structures with other immunoregulatory macromolecules. METHODS: Islets were isolated from Wistar rats using collagenase digestion and a discontinuous Ficoll-Histopaque gradient and subsequently encapsulated in 2% alginate. After coating with a polyelectrolyte multilayer of polylysine and alginate, a polymeric membrane-mimetic coating was applied to the capsule surface. Individual islet viability was evaluated at each stage of the encapsulation procedure by use of a two-color live/dead cell assay. Preservation of islet function was determined by transplanting 1000 encapsulated islets into the peritoneal cavity of streptozotocin-induced diabetic nonobese diabetic NOD/Scid mice. RESULTS: At the end of the coating procedure, the proportion of viable cells within each islet was >50% in 88% of encapsulated rat islets and >75% in over half of the encapsulated cohort. Nonfasting blood glucose levels normalized within 24 hours after transplantation (n = 8). Normoglycemia has been maintained in all mice with the longest time course being 73 days thus far. CONCLUSIONS: We have demonstrated that microencapsulated islets coated with a membrane-mimetic thin film can be generated with high viability in vitro and persistent function in vivo.

Surgical intervention for complications caused by femoral artery catheterization in pediatric patients.

PURPOSE: This study evaluated the risk factors and surgical management of complications caused by femoral artery catheterization in pediatric patients. METHODS: From January 1986 to March 2001, the hospital records of all children who underwent operative repairs for complications caused by femoral artery catheterization were reviewed. A prospective cardiac data bank containing 1674 catheterization procedures during the study period was used as a means of determining risk factors associated with iatrogenic femoral artery injury. RESULTS: Thirty-six operations were performed in 34 patients (age range, 1 week-17.4 years) in whom iatrogenic complications developed after either diagnostic or therapeutic femoral artery catheterizations during the study period. Non-ischemic complications included femoral artery pseudoaneurysms (n = 4), arteriovenous fistulae (n = 5), uncontrollable bleeding, and expanding hematoma (n = 4). Operative repairs were performed successfully in all patients with non-ischemic iatrogenic femoral artery injuries. In contrast, ischemic complications occurred in 21 patients. Among them, 14 patients had acute femoral ischemia and underwent surgical interventions including femoral artery thrombectomy with primary closure (n = 6), saphenous vein patch angioplasty (n = 6), and resection with primary anastomosis (n = 2). Chronic femoral artery occlusion (> 30 days) occurred in seven patients, with symptoms including either severe claudication (n = 4) or gait disturbance or limb growth impairment (n = 3). Operative treatments in these patients included ileofemoral bypass grafting (n = 5), femorofemoral bypass grafting (n = 1), and femoral artery patch angioplasty (n = 1). During a mean follow-up period of 38 months, no instances of limb loss occurred, and 84% of children with ischemic complications eventually gained normal circulation. Factors that correlated with an increased risk of iatrogenic groin complications that necessitated surgical intervention included age younger than 3 years, therapeutic intervention, number of catheterizations (>or= 3), and use of 6F or larger guiding catheter. CONCLUSION: Although excellent operative results can be achieved in cases of non-ischemic complications, acute femoral occlusion in children younger than 2 years often leads to less satisfactory outcomes. Operative intervention can provide successful outcome in children with claudication caused by chronic limb ischemia. Variables that correlated with significant iatrogenic groin complications included a young age, therapeutic intervention, earlier catheterization, and the use of a large guiding catheter.

PR-39 coordinates changes in vascular smooth muscle cell adhesive strength and locomotion by modulating cell surface heparan sulfate-matrix interactions.

PR-39 is proline-rich peptide produced at sites of tissue injury. While the functional properties of this peptide have not been fully defined, PR-39 may be an important regulator of processes related to cell-matrix adhesion since it reportedly upregulates syndecan-4, which is a critical determinant of focal adhesion formation. The ability of PR-39 to modulate the adhesion and chemokinetic migration behavior of arterial smooth muscle cells (SMCs) in a fashion coordinated with syndecan-4 expression was investigated. Treatment of SMCs with PR-39 did not alter syndecan-1 mRNA, but did induce a two-fold increase in syndecan-4 mRNA (P < 0.0001) and significantly enhanced cell surface expression of both syndecan-4 (P < 0.01) and heparan sulfate (HS) (P < 0.05). These observations were consistent with an observed increase in cell-matrix adhesive strength (P < 0.05) and a reduction in cell speed (P < 0.01) on fibronectin-coated substrates. Incubation of PR-39 treated cells with a soluble fibronectin derived heparin-binding peptide, as a competitive inhibitor of heparan sulfate/matrix interactions, abolished these effects. These data suggest that PR-39 mediated alterations of cell adhesion and motility may be related, in part, to the increased expression of heparan sulfate glycosaminoglycans (GAGs) that accompany the upregulation of cell surface syndecan-4. Furthermore, this investigation supports the notion that factors which control syndecan-4 expression may play an important role in regulating adhesion related cell processes.

Synthesis and terminal functionalization of a polymerizable phosphatidylethanolamine.

We report the design and synthesis of bifunctional phospholipid conjugates, which contain a polymerizable acrylate group and a terminal linker, such as biotin or N-(epsilon-maleimidocaproyl (EMC), to facilitate bioconjugation reactions. The lipid conjugate can be used to generate a multifunctional substrate-supported phospholipid film that is further stabilized via in-situ photocopolymerization.

Early experience with the bifurcated Excluder endoprosthesis for treatment of the abdominal aortic aneurysm.

PURPOSE: This report describes our initial experience with the modular, bifurcated Excluder endoprosthesis and its safety and efficacy in the primary endovascular repair of infrarenal abdominal aortic aneurysms (AAAs). METHODS: AAAs (mean diameter, 58.2 +/- 14.3 mm) were repaired in 19 patients with this device between March 1999 and January 2000. The mean age of patients was 71.8 +/- 8.4 years (range, 57-86 years). This modular device was inserted through an 18F introducer sheath placed in one femoral artery, and the contralateral artery was cannulated with a 12F introducer sheath. All procedures were performed in a standard operating room with angiographic capabilities. RESULTS: Endograft deployment was successful in all patients. The average surgical time was 135 +/- 37 minutes, with a mean blood loss of 229 +/- 138 mL. In eight patients, the use of either aortic or iliac extenders was required for enhanced sealing or additional length. An external iliac artery dissection occurring at the time of endograft insertion was successfully treated with a Wallstent. Type II leaks initially found to be present by means of intraoperative completion angiography had spontaneously thrombosed by the 1-month follow-up computed tomography scan. There was one perioperative death (5.3%). Complications included superficial wound infections (n = 3) and a nonfatal myocardial infarction (n = 1). The mean length of hospital stay was 2.9 +/- 1.2 days, and only six patients required intensive care. Endoleaks were seen in four patients (21%) by means of the 30-day computed tomography scan; three of these endoleaks had spontaneously sealed at the time of the 6-month follow-up examination (5.5% 6-month endoleak rate). Aneurysm size did not increase in the patients with leaks. CONCLUSION: The Excluder endoprosthesis was an effective means of excluding an infrarenal AAA from the systemic circulation in this selected group of patients. The smaller sheath sizes may increase the pool of potential candidates. Further study of this device is warranted, and continued assessment of the long-term durability of the device will be necessary.

Detection of isolated hook fractures 36 months after implantation of the Ancure endograft: a cautionary note.

Two cases of delayed (36-month) Ancure hook fracture are reported in patients who experienced a decrease in aneurysm size and no evidence of endoleak. Both devices used redesigned hooks and are otherwise identical to those devices currently used in clinical practice. Notably, hook fractures were not visualized on all abdominal radiographic views, nor were they noted on the final "institutional" report by the reviewing radiologist. Careful clinical follow-up with multiple-view abdominal radiographs remains essential for all patients treated with an endovascular graft, with particular attention directed to the integrity of the metal components. The broader clinical significance of this observation with respect to the Ancure endograft remains to be defined.

Soluble heparin-binding peptides regulate chemokinesis and cell adhesive forces.

The ability of a soluble heparin-binding peptide sequence derived from fibronectin to modulate the adhesion and chemokinetic migration behavior of arterial smooth muscle cells was assessed using a novel glass microsphere centrifugation assay and automated time-lapse fluorescence videomicroscopy, respectively. Treatment of cells grown on fibronectin-coated substrates with the soluble heparin-binding peptide resulted in the disassembly of focal adhesions, as assessed by immunohistochemical staining. These observations were consistent with an observed dose-dependent two- to fivefold reduction in cell-substrate adhesive strength (P < 0.001) and a biphasic effect on migration speed (P < 0.05). Moreover, heparin-binding peptides induced a twofold reduction (P < 0.01) in two-dimensional cell dispersion in the presence of a non-heparin-binding growth factor, platelet-derived growth factor-AB (PDGF-AB). Heparin-binding peptides were unable to mediate these effects when cells were grown on substrates lacking a heparin-binding domain. These data support the notion that competitive interactions between cell surface heparan sulfates with heparin-binding peptides may modulate chemokinetic cell migration behavior and other adhesion-related processes.

Endovascular revascularization of renal artery stenosis: technical and clinical results.

PURPOSE: The natural history of renal artery stenosis is progression with subsequent deterioration of kidney function and development of renovascular hypertension. Percutaneous transluminal renal angioplasty is effective in the treatment of nonostial lesions but less effective for ostial stenoses. Because of the poor technical success experienced with percutaneous transluminal renal angioplasty, stenting of ostial stenoses is becoming the standard of endovascular care. In this retrospective study we analyzed the technical and clinical outcomes after renal artery stenting in 73 consecutive patients. PATIENTS AND METHODS: From July 1992 to January 1999, 88 Palmaz stents were deployed in 85 renal artery stenoses in 73 patients, with a mean age of 67.9 +/- 9.4 years. Twelve patients (16%) underwent bilateral stent placement. Atheromatous lesions were the most prevalent (99%: 82% ostial, 16% nonostial). Most stents were implanted for suboptimal balloon dilation (52%) or dissection (24%). Mean percent stenosis was 86% +/- 12%. Renal insufficiency (creatinine level > or = 1.5 mg/dL) was present in 50 (68%) patients, and uncontrolled hypertension (systolic > or = 160 mm Hg or diastolic > or = 90 mm Hg with more than two medications) was present in 57 (78%). RESULTS: Primary technical success was achieved in 89%. At the initial procedure, three additional stents were placed for residual stenoses, and urokinase was used to treat one intraprocedural stent thrombosis, resulting in an assisted primary technical success rate of 94%. Major complications occurred in 9.1% of stents placed: access artery thrombosis (n = 4), renal artery extravasation (n = 1), renal artery thrombosis (n = 1), and hematoma requiring operation (n = 2). Long-term clinical data were available on 69 (95%) patients at 20 +/- 17 months. Overall, a significant decrease in systolic and diastolic pressures (P <.001) and reduction of medication (P <.01) were noted without a change in renal function (P = NS). Angiography was performed on 22 patients at 11.3 +/- 10.3 months for persistent or worsening renal function or hypertension or for other reasons; 10 patients had significant restenoses in 14 renal arteries. CONCLUSION: Our retrospective analysis demonstrates that endovascular stenting of renal artery stenosis in patients with poorly controlled hypertension or deteriorating renal function is a safe and effective alternative treatment to surgical management.

Age versus comorbidities as risk factors for complications after elective abdominal aortic reconstructive surgery.

PURPOSE: This study estimated the association between age and in-hospital postoperative complications, controlling for known or suspected risk factors, in a series of patients undergoing elective abdominal aortic reconstructive surgery (AAR). METHODS: This retrospective cohort study of outcome data with multivariate logistic regression analysis was conducted at Emory University Hospital, a tertiary care, university-affiliated hospital. All patients undergoing elective AAR between Jan 1, 1986, and Aug 1, 1996, were included (n = 856). An estimate of the odds ratio (OR) and 95% CI for the association between patient age and in-hospital major morbidity or mortality after elective AAR was made, controlling for significant risk factors. RESULTS: Among the 856 patients, 170 had a nonfatal complication (136 with major and 34 with minor complications), and 11 patients (1.3%) died. The final logistic regression model demonstrated a mild association between increasing age and rate of major postoperative complications, including death (for each increase in age of 10 years: OR, 1.23; 95% CI, 1.00-1.52; P =.052). Other significant covariates in the final model included cardiac disease (OR, 2.84; 95% CI, 1.18-6.86; P =.020), pulmonary disease (OR, 1.96; 95% CI, 1.35-2.84; P =.0004), and renal disease (OR, 2.57; 95% CI, 1.66-3.99; P =.0001). Increasing age was associated with a moderate increase in the rate of death (for each increase in age of 10 years: OR, 2.74; 95% CI, 1.22-6.16; P =.015) in a model with cardiac disease as the only significant covariate (OR, 14.67; 95% CI, 3.46-62.16; P =.0003). CONCLUSION: For patients undergoing elective AAR, increasing patient age is associated with a small increase in risk for in-hospital morbidity or mortality. However, significant cardiac, pulmonary, or renal disease is associated with a much greater risk of postoperative complications, and, therefore, advanced age should not be the sole basis of exclusion for otherwise suitable candidates for elective AAR.

Mid-term results after endovascular repair of the abdominal aortic aneurysm.

PURPOSE: As a minimally invasive strategy for the treatment of patients with abdominal aortic aneurysm (AAA), endovascular repair has been embraced with enthusiasm because of the promise of achieving a durable result with a reduced risk of perioperative morbidity and mortality. Our mid-term experience with endovascular AAA repair was assessed by examining early and late clinical outcome in concurrent cohorts of patients stratified either as low-risk or as at increased-risk for intervention. METHODS: From April 1994 to December 1999, endovascular AAA repair was performed in 104 patients with commercially available systems. A subset of patients considered at increased risk for intervention (n = 51) were categorized as such based on a pre-existing history of ischemic coronary artery disease (73%), with documentation of myocardial infarction (57%) or congestive heart failure (29%), or because of the presence of chronic obstructive pulmonary disease, liver disease, or malignancy. RESULTS: The perioperative mortality rate (30-day) was 7.8% for patients at increased risk compared with 1.9% among those classified as low-risk (P = NS). There was no difference between groups in age (72 +/- 7 years vs 74 +/- 7 years; mean +/- SD), surgical time (221 +/- 90 minutes vs 192 +/- 68 minutes), blood loss (437 +/- 402 mL vs 331 +/- 238 mL), postoperative hospital stay (4.4 +/- 2.7 days vs 4.2 +/- 2.5 days), or days in the intensive care unit (1.2 +/- 1.6 days vs 0.6 +/- 1.3 days). Patients at increased risk of intervention had larger aneurysms than patients at low risk (58 +/- 11 mm vs 52 +/- 12 mm; P < .05). Stent grafts were successfully implanted in 47 (92%) patients at increased risk versus 50 (94%) patients at low risk (P = NS). Conversion rates to open operative repair were similar in increased-risk and low-risk groups at 3.9% and 5.7%, respectively. The initial endoleak rate was 21% versus 18% based on the first computed tomography performed (either at discharge or 1 month; P = NS). To date, patients at increased risk have been monitored for 14.6 +/- 12.4 months, and patients at low risk have been monitored for 17.7 +/- 15.0 months. Kaplan-Meier analysis for cumulative patient survival demonstrated a reduced probability of survival among those patients initially classified as at increased risk for intervention (P < .05, Mantel-Cox test). Both cohorts had similar 2-year clinical success rates of approximately 75%. CONCLUSION: Despite the use of an endovascular approach for aneurysm treatment, the risk of perioperative death and morbidity remains present for all patients including those who have no significant medical comorbidity. Moreover, although clinical success rates are comparable in both patient groups, 2 years after endovascular repair was performed, at least one in four patients was classified as a clinical failure. Given the continued uncertainty associated with clinical outcome and the need for close life-long surveillance, caution is dictated in advocating endovascular treatment for the patient who is otherwise considered an ideal candidate for standard open surgical repair.

Endovascular revascularization of renal artery stenosis in the solitary functioning kidney.

The treatment of renal artery stenosis by angioplasty and stenting is an effective and accepted alternative to surgery for the treatment of renovascular hypertension and preservation of renal function. We report the technical and clinical outcomes of renal artery stenting in patients with a solitary functioning kidney and renal artery stenosis. From October 1993 to November 1999, 30 stents were placed in the renal arteries of 27 patients (mean age 72+/-8 years) with a solitary functioning kidney and azotemia. The mean diameter renal artery stenosis was 86+/-14%. The mean preprocedure serum creatinine (Cr) level was 3.0+/-1.5 mg/dL (range 1.5-7.5 mg/dL), arterial blood pressure was 171+/-29/85+/-13 mmHg, and the number of antihypertensive drugs was 2.9+/-1.1. Indications for stenting were suboptimal balloon dilation (n = 16), intimal dissection (n = 6), and restenosis following angioplasty (n = 5). Atherosclerotic ostial lesions were present in 25 (93%) of 27 renal arteries. This represents the largest series of renal artery stenting in patients with a solitary functioning kidney, and demonstrates this treatment modality to be a relatively safe alternative to conventional surgery in this high-risk patient group. Most (74%) of the patients in this series had improved or stabilized renal function. Further efforts to define preprocedural indicators of success are necessary to identify the patients who may benefit from revascularization of their solitary kidney.

High-resolution analysis of engineered type I collagen nanofibers by electron microscopy.

Collagen nanofibers were generated at ambient temperature and pressure by electrospinning a 1 wt% solution of type I collagen and polyethylene oxide. Products were imaged with high-resolution scanning electron microscopy (HRSEM) at medium (approximately 30,000 x) and high magnifications (approximately 100,000 x) and with transmission electron microscopy (TEM). The capacity to produce collagen nanofibers may lead to the generation of extracellular matrix-based fabrics with applications in the fields of wound healing and tissue engineering.

Engineered collagen-PEO nanofibers and fabrics.

Type I collagen-PEO fibers and non-woven fiber networks were produced by the electrospinning of a weak acid solution of purified collagen at ambient temperature and pressure. As determined by high-resolution SEM and TEM. fiber morphology was influenced by solution viscosity, conductivity, and flow rate. Uniform fibers with a diameter range of 100-150 nm were produced from a 2-wt% solution of collagen-PEO at a flow rate of 100 microl min(-1). Ultimate tensile strength and elastic modulus of the resulting non-woven fabrics was dependent upon the chosen weight ratio of the collagen-PEO blend. 1H NMR dipolar magnetization transfer analysis suggested that the superior mechanical properties, observed for collagen-PEO blends of weight ratio 1:1, were due to the maximization of intermolecular interactions between the PEO and collagen components. The process outlined herein provides a convenient, non-toxic, non-denaturing approach for the generation collagen-containing nanofibers and non-woven fabrics that have potential application in wound healing, tissue engineering, and as hemostatic agents.

Subclavian artery disruption resulting from endovascular intervention: treatment options.

Endovascular intervention is a commonly accepted form of treatment in patients with subclavian artery stenosis. Complications will undoubtedly occur as the utility of catheter-based intervention continues to rise. We report two cases of subclavian artery disruption as a result of endovascular intervention. One patient had contrast extravasation after the deployment of a balloon-expandable stent in a stenotic subclavian artery, and the arterial injury was successfully treated with balloon tamponade. A second patient had a large subclavian pseudoaneurysm 4 months after a balloon-expandable stent placement. Successful repair was achieved in this patient by means of arterial reconstruction with a prosthetic bypass graft. These cases illustrate different therapeutic methods of treating subclavian artery rupture due to endovascular intervention.

A porcine model of carotid artery thrombosis for thrombolytic therapy and angioplasty: application of PTFE graft-induced stenosis.

PURPOSE: To develop a porcine carotid artery thrombosis model for the evaluation of thrombolytic therapy and adjunctive angioplasty procedures. METHODS: Bilateral carotid thrombosis was induced in 16 pigs using endothelial crush injury followed by external polytetrafluoroethylene (PTFE, 5 x 2 cm2) wrap placement to create segmental carotid stenosis. Light microscopy was used to examine thrombus composition. Selective carotid catheterization was performed via a femoral approach. Two hours following carotid artery occlusion, a urokinase (250,000 IU) and heparin (1000 U) solution was pulse-sprayed in 1 carotid artery while the contralateral vessel received the control saline vehicle. The efficacy of thrombolytic therapy was assessed using carotid arteriography and intravascular ultrasound. The feasibility and technical efficacy of balloon angioplasty within the carotid stenosis model were also evaluated. RESULTS: Carotid artery occlusion occurred in 30 +/- 6 minutes following endothelial injury plus PTFE wrap placement. Histological examination of carotid arteries showed endothelial irregularity with fibrin-rich and platelet-rich thrombus. Urokinase was effective in recanalizing all occluded arteries (100%), while the control saline vehicle showed no effective thrombolysis (p < 0.001). Angioplasty was successful in restoring normal diameter in all arteries (100%). CONCLUSIONS: This carotid artery thrombosis model, which incorporates intimal injury with segmental stenosis, is simple to create and reproducible. It provides not only a model for the evaluation of thrombolytic therapy but also a practical training tool for adjunctive endovascular interventions.

Embryology, anatomy, and surgical exposure of the great abdominal vessels.

This article describes the embryology of the abdominal aorta and the anatomic features of its major visceral branches, including the celiac, superior mesenteric, and inferior mesenteric arteries. The common anatomic variants of these visceral vessels also are reviewed. Various operative techniques to gain surgical exposure to these vessels are described.

An endovascular model of carotid stenosis for the evaluation of thrombolysis and angioplasty.

PURPOSE: To develop a porcine carotid artery thrombosis model using a novel stent-graft device to evaluate the efficacy of thrombolytic therapy and angioplasty procedures. METHODS: An endovascular device made from a tapered polytetrafluoroethylene graft inverted in a self-expanding nitinol stent was delivered to bilateral carotid arteries via a right femoral approach in 16 pigs. Carotid thrombotic occlusion ensued from flow stasis created by the intrastent stenosis. Via selective carotid catheterization from a femoral approach, urokinase (250,000 IU) was pulse-sprayed in one carotid artery while a control saline solution was infused in the contralateral vessel; delivery times were 1 hour, 8 hours, 3 days, or 6 days after carotid occlusion (4 animals per time period). After thrombolysis, balloon angioplasty was performed to maintain carotid patency. Arteriography and intravascular ultrasound were used to evaluate the efficacy of thrombolysis. Light microscopy was used for histological analysis of the thrombus. RESULTS: Carotid artery occlusion occurred in 15+/-8 minutes after stent-graft placement in all animals. Urokinase was effective in recanalizing all occluded arteries in the 1-hour, 4-hour, and 3-day groups (100%) but was effective in only 2 of 4 animals in the 6-day group (p < 0.05). Overall thrombolytic efficacy was 78%+/-7%. Control saline solution showed no thrombolytic effect (p < 0.001). Angioplasty successfully restored normal luminal diameter in all fully lysed arteries (100%). Histological analysis showed fibrin-predominant thrombus with a varying degree of platelet deposition. CONCLUSIONS: This endovascular approach, which creates a carotid stenosis using this novel stent-graft device, is reliable in producing carotid thrombosis. In our model, thrombolytic therapy was effective in restoring luminal patency, and the intraluminal stenosis is amenable to balloon angioplasty. The model is useful for the evaluation of antithrombotic therapy and adjunctive endovascular interventions.