Biomedical subjects

Omaida C Velazquez

Publications and source records attributed to Omaida C Velazquez.

At least 19 recordsLinked to original sources

PubMed2006

A comparison of renal function between open and endovascular aneurysm repair in patients with baseline chronic renal insufficiency.

OBJECTIVE: Endovascular aneurysm repair (EVAR) is rapidly becoming the predominant technique for repair of abdominal aortic aneurysms. Results from current studies, however, are conflicting on the effect of EVAR on renal function compared with standard open repair. Furthermore, data for open repair in patients with baseline renal insufficiency suggests worse outcomes, including renal function. This analysis compared the effects of open repair vs EVAR on renal function in patients with baseline renal insufficiency. METHODS: We reviewed our records for patients with preoperative chronic renal insufficiency (serum creatinine, 1.5 mg/dL) who underwent open repair or EVAR between 1999 and 2004. The same group of vascular surgeons at a single institution performed aneurysm repair on 98 patients: 46 open (37 men, 9 women) and 52 EVAR (50 men, 2 women). Preoperative, postoperative, and follow-up serum creatinine and creatinine clearance were compared, as was the development of postoperative renal impairment (increase in serum creatinine >30%). RESULTS: Serum creatinine and creatinine clearance were not statistically different between the open and EVAR groups during any time period studied. Likewise when comparing the magnitude of change in serum creatinine in patients between the postoperative and follow-up times with preoperative values, no significant differences existed between the open and EVAR groups. When the change in serum creatinine over time within each group was compared, however, the open group had a significant increase in serum creatinine postoperatively (2.43 +/- 1.20 vs 2.04 +/- 0.64, P = .012), which returned to baseline during follow-up (1.96 +/- 0.94, P = .504). Although serum creatinine in the EVAR group increased compared with preoperative values of 2.04 +/- 0.55 (postoperative, 2.27 +/- 1.04; follow-up, 2.40 +/- 1.37), this failed to reach statistical significance for the postoperative (P = .092) or follow-up (P = .081) periods. A similar pattern was noted in creatinine clearance. Postoperative renal impairment was noted in 13 open (28%) and 15 EVAR patients (29%) and was not statistically different between groups. Overall, two patients (4.3%) from the open group and four (7.7%) from the EVAR group required hemodialysis; one in the EVAR group required permanent hemodialysis. This difference was not statistically significant (P = .681). CONCLUSIONS: Open and endovascular repair of abdominal aortic aneurysms in patients with pre-existent renal insufficiency can be performed safely with preservation of renal function. In contrast to previous reports, no significant differences existed between open repair and EVAR in postoperative alterations in renal function. Although a significant increase in serum creatinine develops in patients with renal insufficiency postoperatively with open repair, this appears to be transient, and preoperative renal dysfunction alone should not exclude either approach. After EVAR, patients with pre-existing renal insufficiency continue to be at risk for progressive renal dysfunction, and protective measures should be taken to preserve renal function in this patient population.

Adult↗

PubMed2006

Endothelial progenitor cell release into circulation is triggered by hyperoxia-induced increases in bone marrow nitric oxide.

Endothelial progenitor cells (EPC) are known to contribute to wound healing, but the physiologic triggers for their mobilization are often insufficient to induce complete wound healing in the presence of severe ischemia. EPC trafficking is known to be regulated by hypoxic gradients and induced by vascular endothelial growth factor-mediated increases in bone marrow nitric oxide (NO). Hyperbaric oxygen (HBO) enhances wound healing, although the mechanisms for its therapeutic effects are incompletely understood. It is known that HBO increases nitric oxide levels in perivascular tissues via stimulation of nitric oxide synthase (NOS). Here we show that HBO increases bone marrow NO in vivo thereby increasing release of EPC into circulation. These effects are inhibited by pretreatment with the NOS inhibitor l-nitroarginine methyl ester (l-NAME). HBO-mediated mobilization of EPC is associated with increased lower limb spontaneous circulatory recovery after femoral ligation and enhanced closure of ischemic wounds, and these effects on limb perfusion and wound healing are also inhibited by l-NAME pretreatment. These data show that EPC mobilization into circulation is triggered by hyperoxia through induction of bone marrow NO with resulting enhancement in ischemic limb perfusion and wound healing.

Animals↗

PubMed2006

Femoral neuropathy following retroperitoneal hemorrhage: case series and review of the literature.

Femoral neuropathy due to retroperitoneal hematoma has been infrequently described in the literature. While occasionally due to trauma, it has been most commonly reported in association with various bleeding diatheses and therapeutic anticoagulation. As the indications for the use of anticoagulants and antiplatelet agents increase, associated hemorrhagic complications will likely also increase. The management of retroperitoneal hematoma with consequent femoral nerve palsy remains controversial. We present a series of four cases of femoral nerve palsy due to retroperitoneal hematoma managed by surgical decompression. Hematoma evacuation at the time of the development of femoral neuropathy results in immediate benefit, with greater likelihood of a return to pre-event neurological status. Delays in operative treatment, despite the presence of a neurological deficit, may lead to significant and prolonged neurological dysfunction. Surgical decompression should be highly considered in all patients who develop femoral neuropathy from a retroperitoneal hematoma.

Adolescent↗

PubMed2006

Inhibition of endothelial cell proliferation by Notch1 signaling is mediated by repressing MAPK and PI3K/Akt pathways and requires MAML1.

The requirement for Notch signaling in vasculogenesis and angiogenesis is well documented. In a previous study, we showed that activation of the Notch pathway in endothelial cells induces differentiation-associated growth arrest; however, the underlying mechanism remains to be elucidated. Here, we show that activation of the Notch pathway by either stimulation of cell surface Notch receptors with crosslinked soluble delta-like 4 (sDll4)/Jagged1 (sJag1) or constitutive expression of the Notch1 intracellular domain (N(IC)) suppresses endothelial cell proliferation. This suppression is mediated by the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. Following Notch1 activation, both pathways were suppressed in endothelial cells, and alterations in MAPK or PI3K/Akt pathway activity reversed Notch1-induced growth inhibition. Furthermore, we found the effect of Notch1 on endothelial cells to require Mastermind-like (MAML). Overexpression of a dominant-negative mutant of MAML1 antagonized the effects of activated Notch1 on the MAPK and PI3K/Akt pathways. Ectopic expression of Hairy/Enhancer of Split 1 (HES1) consistently reproduced the inhibitory effect of N(IC) on endothelial cell proliferation. Together, our data demonstrate that the Notch/MAML-HES signaling cascade can regulate both MAPK and PI3K/Akt pathways, which suggests a molecular mechanism for the inhibitory effect of Notch signaling on endothelial cell proliferation.

Cell Proliferation↗

PubMed2006

Emergency endovascular deployment of stent graft in the ascending aorta for contained rupture of innominate artery pseudoaneurysm in a pediatric patient.

Endovascular approaches to treat aortic diseases have become an important alternative to open surgical intervention in aortic pathologies. We report a case of an emergency placement of a stent graft in a 16-year-old boy with a contained rupture of an innominate artery pseudoaneurysm. This patient had been previously treated for a mediastinal T-cell lymphoma and underwent mediastinal chemoradiation. He developed tracheal stenosis, requiring multiple tracheal reconstructive surgical procedures, and subsequently emergency ligation of a tracheal-innominate fistula. A pseudoaneurysm of the previously ligated innominate artery developed. Despite coil embolization, it continued to enlarge, requiring emergency endovascular intervention. A pseudoaneurysm of the previously ligated innominate artery subsequently developed, and despite coil embolization, it continued to enlarge, which required emergency endovascular intervention.

Adolescent↗

PubMed2006

The bone marrow-derived endothelial progenitor cell response is impaired in delayed wound healing from ischemia.

OBJECTIVE: Vasculogenesis relies on the recruitment of bone marrow-derived endothelial progenitor cells (BMD EPCs) and is stimulated by tissue-level ischemia. We hypothesized that the BMD EPC response is impaired in ischemic wounds and studied the relationship between BMD EPCs and wound healing. METHODS: We used transgenic Tie-2/LacZ mice, which carry the beta-galactosidase (beta-gal) reporter gene under Tie-2 promoter control. Wild-type mice were lethally irradiated and reconstituted with Tie-2/LacZ bone marrow. Four weeks later, the mice underwent unilateral femoral artery ligation/excision and bilateral wounding of the hindlimbs. Ischemia was confirmed and monitored with laser Doppler imaging. A subset of mice received incisional vs excisional nonischemic bilateral hindlimb wounds, without femoral ligation. Excisional wound closure was measured by using daily digital imaging and software-assisted calculation of surface area. RESULTS: Ischemia resulted in significantly delayed wound healing and differentially affected the number of BMD EPCs recruited to wound granulation tissue and muscle underlying the wounds. At 3 days postwounding, the granulation tissue of the wound base contained significantly fewer numbers of BMD EPCs in ischemic wounds compared with the nonischemic wounds (P < .05). In contrast, significantly more BMD EPCs were present in the muscle underlying the ischemic wounds at this same time point compared with the muscle under the nonischemic wounds (P < .05). In ischemic wounds, eventual wound closure significantly correlated with a delayed rise in BMD EPCs within the wound granulation tissue (Kendall's correlation, -.811, P = .0005) and was significantly associated with a gradual recovery of hindlimb perfusion (P < .0001). By 7 days postwounding, BMD EPCs were incorporated into the neovessels in the granulation tissue. At 14 days and 75 days, BMD EPCs were rarely observed within the wounds. CONCLUSIONS: Granulation tissue of excisional ischemic wounds showed significantly less BMD EPCs 3 days postwounding, in association with significantly delayed wound closure. However, the number of BMD EPCs were increased in ischemic hindlimb skeletal muscle, consistent with the notion that ischemia is a powerful signal for vasculogenesis. To our knowledge, this is the first report identifying a deficit in BMD EPCs in the granulation tissue of ischemic skin wounds and reporting the key role for these cells in both ischemic and nonischemic wound healing.

Animals↗

PubMed2006

Outcomes of accessory renal artery occlusion during endovascular aneurysm repair.

OBJECTIVE: Accessory renal arteries are frequently encountered when patients are evaluated for endovascular abdominal aortic aneurysm repair (EVAR). Some have considered their presence a contraindication to EVAR in fear of endoleak and the end result of renal function. We sought to determine whether the coverage of accessory renal arteries during EVAR was associated with any adverse sequelae. METHODS: Retrospective review of the medical records and computed tomographic scans of all patients undergoing EVAR (1998 to 2003) was performed. Note was made of the presence or absence of accessory renal arteries, hypertension, and renal function. Preoperative computed tomographic images were compared with postoperative images to determine the presence of renal infarction. A control group of 26 consecutive patients without accessory renal arteries was used for comparison of the results of EVAR. RESULTS: EVAR was performed in 550 patients over the study interval. The mean follow-up was 16 months (range, 1-48 months). The average age was 74 years (range, 57-90 years). Thirty-five patients (6.6%; 32 male and 3 female) were documented to have accessory renal arteries; the average number of accessory arteries was 2 (range, 1-4). Bilateral accessory arteries were present in 13 patients: all but 1 patient (n = 34) had a left-sided accessory renal artery, and 23 had a right-sided accessory renal artery. EVAR was performed with a variety of endografts: AneuRx (n = 10), Talent (n = 7), PowerLink (n = 7), Zenith (n = 5), LifePath (n = 4), and Ancure (n = 2). There were no mortalities. Twelve endoleaks were documented: three type I, eight type II, and one type III. The accessory renal arteries were not implicated in any of the endoleaks, and none of these accessory vessels was embolized before or after EVAR. Seven patients (20%) had renal infarcts associated with EVAR that were noted on follow-up computed tomographic scans. The mean follow-up for patients with segmental infarction was 23 months (range, 8-48 months). Hypertensive status did not change in any patient in whom an accessory renal artery had been covered. The average serum creatinine was 1.08 mg/dL (range, 0.6-1.8 mg/dL) before EVAR in patients with accessory renal arteries covered by an endovascular graft and did not change significantly in response to EVAR. Serum creatinine increased almost twofold in two patients but spontaneously resolved in follow-up. The average preoperative creatinine clearance was 79 mL/min (range, 35-166 mL/min) in patients without an accessory renal artery and was 80 mL/min (range, 35-167 mL/min) after EVAR. The average preoperative creatinine clearance was 67 mL/min (range, 31-137 mL/min) in patients with an accessory renal artery and 68 mL/min (range, 45-83 mL/min) in patients with renal infarcts. None of the patients required temporary or permanent dialysis. There was no difference between control patients and patients with covered accessory renal arteries with respect to hypertensive status, presence of renal infarcts, serum creatinine, or creatinine clearance after EVAR. CONCLUSIONS: Occlusion of accessory renal arteries is not associated with clinically significant signs or symptoms, even in patients with mild or moderate renal insufficiency. Sacrifice of accessory renal arteries most commonly does not lead to detectable renal infarction, either clinically or radiographically. When segmental infarction of the kidney does result, it seems to be well tolerated in this group of patients. Accessory renal arteries were not found to contribute to endoleaks and should not be prophylactically embolized.

Aged↗

PubMed2006

Risk factors for restenosis after carotid artery angioplasty and stenting.

OBJECTIVES: With carotid artery stenting (CAS) becoming an ever-increasing procedure, we sought to determine risk factors for in-stent restenosis after CAS. METHODS: Consecutive patients undergoing CAS between January 2002 and October 2004 at a tertiary care hospital were retrospectively reviewed. Patient, filter, and stent selection were left to the discretion of the attending surgeon. High-risk patients were defined by significant comorbidities or a hostile neck (prior surgery or radiation, or both), and risk factor analysis was performed. In-stent restenosis was defined as >60%, and selective angiography was performed on patients with an in-stent restenosis >80% by duplex ultrasound imaging. RESULTS: Reviewed were 101 patients (55 men, 46 women) who underwent 109 CAS procedures. Comorbidities were typical for patients with atherosclerosis. In addition, 38% (n = 41) of procedures were performed in patients who had prior neck surgery, of which 29% (n = 32) had previous ipsilateral carotid endarterectomy. Seventeen patients (16%) had a history of neck cancer, and all had prior neck radiation. Median follow-up was 5 months (range, 0 to 30 months). Neurologic complications included three transient ischemic attacks (2.8%) and one nondisabling stroke (0.9%). There were two myocardial infarctions (1.9%) and no periprocedural deaths (30 days), for a combined stroke, myocardial infarction, and death rate of 2.9%. Asymptomatic in-stent restenosis developed in 12 carotids (11%), five of which required endovascular intervention, with a mean of 6 months to restenosis. Univariate Cox proportional hazard regression models were used to determine risk factors for the development of restenosis. Prior stroke, transient ischemic attack, amaurosis fugax, and prior neck cancer were all significant risk factors. When these significant risk factors from univariate analysis were put into multivariate analysis, however, the only marginally significant risk factor was prior neck cancer (P = .06). Kaplan-Meier analysis revealed a cumulative freedom from in-stent restenosis at 24 months of 88% +/- 6% in patients without neck cancer compared with 27% +/- 17% (P = .02) in patients with neck cancer. CONCLUSIONS: CAS has been shown to be safe and effective in high-risk patients, with minimal adverse events.

Adult↗

PubMed2005

Stem cell mobilization by hyperbaric oxygen.

We hypothesized that exposure to hyperbaric oxygen (HBO(2)) would mobilize stem/progenitor cells from the bone marrow by a nitric oxide (*NO) -dependent mechanism. The population of CD34(+) cells in the peripheral circulation of humans doubled in response to a single exposure to 2.0 atmospheres absolute (ATA) O(2) for 2 h. Over a course of 20 treatments, circulating CD34(+) cells increased eightfold, although the overall circulating white cell count was not significantly increased. The number of colony-forming cells (CFCs) increased from 16 +/- 2 to 26 +/- 3 CFCs/100,000 monocytes plated. Elevations in CFCs were entirely due to the CD34(+) subpopulation, but increased cell growth only occurred in samples obtained immediately posttreatment. A high proportion of progeny cells express receptors for vascular endothelial growth factor-2 and for stromal-derived growth factor. In mice, HBO(2) increased circulating stem cell factor by 50%, increased the number of circulating cells expressing stem cell antigen-1 and CD34 by 3.4-fold, and doubled the number of CFCs. Bone marrow *NO concentration increased by 1,008 +/- 255 nM in association with HBO(2). Stem cell mobilization did not occur in knockout mice lacking genes for endothelial *NO synthase. Moreover, pretreatment of wild-type mice with a *NO synthase inhibitor prevented the HBO(2)-induced elevation in stem cell factor and circulating stem cells. We conclude that HBO(2) mobilizes stem/progenitor cells by stimulating *NO synthesis.

Animals↗

PubMed2005

Mineral volume and morphology in carotid plaque specimens using high-resolution MRI and CT.

OBJECTIVE: High-resolution MRI methods have been used to evaluate carotid artery atherosclerotic plaque content. The purpose of this study was to assess the performance of high-resolution MRI in evaluation of the quantity and pattern of mineral deposition in carotid endarterectomy (CEA) specimens, with quantitative micro-CT as the gold standard. METHODS AND RESULTS: High-resolution MRI and CT were compared in 20 CEA specimens. Linear regression comparing mineral volumes generated from CT (VCT) and MRI (VMRI) data demonstrated good correlation using simple thresholding (VMRI=-0.01+0.98VCT; R2=0.90; threshold=4xnoise) and k-means clustering methods (VMRI=-0.005+1.38VCT; R2=0.93). Bone mineral density (BMD) and bone mineral content (BMC [mineral mass]) were calculated for CT data and BMC verified with ash weight. Patterns of mineralization like particles, granules, and sheets were more clearly depicted on CT. CONCLUSIONS: Mineral volumes generated from MRI or CT data were highly correlated. CT provided a more detailed depiction of mineralization patterns and provided BMD and BMC in addition to mineral volume. The extent of mineralization as well as the morphology may ultimately be useful in assessing plaque stability.

Adult↗

PubMed2005

Vascular endothelial growth factor-C promotes vasculogenesis, angiogenesis, and collagen constriction in three-dimensional collagen gels.

OBJECTIVE: Neovascularization, angiogenesis, and collagen constriction are essential for wound healing. We tested whether vascular endothelial growth factor-C (VEGF-C) can promote collagen constriction, capillary sprouting (angiogenesis), and invasion/migration of bone marrow-derived endothelial progenitor cells into collagen (vasculogenesis). METHODS: We used a recently characterized three-dimensional collagen matrix assay with either monolayers of human dermal microvascular endothelial cells (HMVECs) or bone marrow-derived endothelial progenitor cells (BMD EPCs), obtained from Tie-2 LacZ transgenic mice, overlaid with an acellular layer and then a cellular layer of collagen embedded with fibroblasts, that were nontransduced or transduced with either LacZ adenoviral vector (Ad5) or VEGF-C/Ad5. The ability of VEGF-C to enhance fibroblast-mediated collagen constriction was measured, and gels overlying HMVECs or BMD EPCs were co-cultured, harvested, and assayed for HMVEC migration, sprouting, and capillary-like formation; gels containing BMD EPCs were assayed for EPC invasion/migration into the collagen extracellular matrix. RESULTS: VEGF-C significantly increased collagen constriction and formation of capillary-like structures with true lumina (P < .05) assessed by von Willebrand factor and VEGF receptor-2 immunoassaying. VEGF-C induced a significant increase in HMVEC migration, tubular polarization, and branching sprouts associated with a significant up-regulation of membrane type 1 matrix metalloproteinase (MT1-MMP) ( P < .05). Fibroblasts were necessary to support BMD-EPC invasion/migration from the monolayer into the collagen. Moreover, fibroblasts overexpressing VEGF-C significantly enhanced EPC invasion/migration ( P < .05) into the extracellular matrix by two-fold, and this effect could not be achieved with equivalent levels of exogenous VEGF-C in the absence of fibroblasts. The addition of a soluble VEGF-C competitor protein only partially inhibited these responses, reducing the EPCs by three-fold, but significant numbers of EPCs still invaded/migrated into the extracellular matrix, suggesting that other fibroblast-specific signals also contribute to the vasculogenic response. CONCLUSION: Fibroblast-specific expression of VEGF-C promotes collagen constriction by fibroblasts and enhances microvascular endothelial cell migration, branching, and capillary sprouting in association with up-regulating MT1-MMP expression. Fibroblasts are necessary for BMD EPC invasion/migration into collagen, and their overexpression of VEGF-C enhances this fibroblast-mediated vasculogenic effect. Collectively, these findings suggest a role for VEGF-C in multiple biologic steps required for wound healing (angiogenesis, vasculogenesis, and collagen constriction). CLINICAL RELEVANCE: Ischemic wound healing remains an unsolved problem with no previously identified molecular target for therapeutic intervention. This study demonstrates that VEGF-C overexpression by fibroblasts stimulates multiple biologic processes known to impact wound healing, such as collagen constriction, capillary sprouting, and EPC invasion and migration through extracellular matrix. Most ischemic wounds fail to heal and frequently lead to major limb amputation. Available cytokine ointments are ineffective, and revascularization is often not technically feasible. Even when these procedures are accomplished, many ischemic wounds frequently still do not heal because of multifactorial tissue level impairments in the fibroblastic and neovascularization responses at the wound base. Our findings identify an important role for two novel tissue level targets, dermis-derived fibroblasts and VEGF-C, in collagen constriction, angiogenesis, and postnatal vasculogenesis from BMD EPCs. Thus the findings are particularly relevant to the unsolved clinical problem of ischemic wound healing.

Animals↗

PubMed2005

Normal human fibroblasts enable melanoma cells to induce angiogenesis in type I collagen.

BACKGROUND: We previously reported that fibroblasts induce human microvascular endothelial cells (HMVECs) to differentiate from monolayer to capillarylike morphology. We now test the hypothesis that fibroblasts modulate angiogenesis in melanoma cells. METHODS: We tested 12 human melanoma lines (2 radial growth phase (RGP), 3 vertical growth phase (VGP), and 7 metastatic (MM)) for ability to induce HMVECs to invade/migrate into collagen and form capillarylike networks. HMVEC monolayers were overlaid with 3-dimensional collagen gels embedded with melanoma cells alone (M), fibroblasts alone (F), or a 1:1 mixture of the 2 cells (M+F). After 5 days, gels were removed, fixed, and HMVEC networks were quantified by von Willebrand's factor (vWF) immunofluorescence. The influence of soluble factors on HMVEC invasion/migration into collagen was assessed with the use of acellular 3-D collagen gels overlaid on HMVEC monolayers, cultured with conditioned media (CM) derived from monolayers of M, F, or M+F. Angiogenic growth factors involved in the observed invasion/migration were identified with the use of a RayBio Cytokine Antibody Array (RayBiotech, Norcross, Ga). RESULTS: Cell line-specific variability in melanoma-supported angiogenesis was observed only when in combination with fibroblasts (analysis of variance [ANOVA], P < .01). Melanoma plus fibroblasts uniformly resulted in a significantly higher angiogenic response than melanoma alone (P < .05). One vertical growth phase and one metastatic melanoma line, while weakly angiogenic alone, induced significantly higher angiogenesis than either fibroblast or melanoma alone (P < .05) when combined with fibroblasts. CM from M or M+F induced significantly less HMVEC invasion/migration into collagen than CM from fibroblasts alone. Interleukin 8, monocyte chemotactic protein-1, and tissue inhibitor of metalloproteinase-2 were identified as significantly elevated in the media derived from M+F cultures, compared with either cell type alone. CONCLUSION: To our knowledge, this is the first report demonstrating that melanoma-supported angiogenesis in collagen is more significantly influenced by normal skin-derived fibroblasts than by the intrinsic biology of the melanoma cell type. Interleukin 8, monocyte chemotactic protein-1, and tissue inhibitor of metalloproteinase-2 are implicated as potential paracrine factors regulating this observed effect.

Angiogenic Proteins↗

PubMed2005

Use of CT angiography to classify endoleaks after endovascular repair of abdominal aortic aneurysms.

PURPOSE: Accurate endoleak detection and classification is critical for the follow-up of patients who have undergone endovascular aneurysm repair (EVAR). This determination is often made with computed tomography angiography (CTA). This investigation was performed to determine the accuracy of CTA in the classification of endoleaks in patients who have undergone EVAR. MATERIALS AND METHODS: Thirty-six patients with endoleaks underwent both CTA and conventional contrast digital subtraction angiography (DSA) to determine endoleak etiology. Two independent radiologists determined the source of the endoleak based on a retrospective review of the CTA. The results of the CTA-based endoleak classification were compared to the reference standard, contrast DSA. RESULTS: There was agreement regarding endoleak classification between CTA and DSA on 86% of the patients (31 of 36 patients). Correlation between the CTA reading of the two readers was 94% (34 of 36 patients), yielding a kappa statistic of 0.8. In three patients, the CTA reading incorrectly classified endoleaks as type 2 when the endoleaks were actually type 1 endoleaks on DSA. One patient was incorrectly classified as having a type 1 endoleak on CTA when it was a type 2 endoleak on DSA. Finally, one patient had a type 1 endoleak on DSA that was incorrectly classified as a type 3 endoleak on CTA. The change in CTA endoleak classification based on the DSA resulted in a significant change in patient management in four of the 36 patients (11%). CONCLUSIONS: Endoleak classification based on CTA correlates fairly well with DSA findings. However, optimal endoleak management requires performance of selective angiograms with DSA to classify endoleaks that are detected on CTA.

Angiography↗

PubMed2004

The utility of commercially available endografts in the treatment of contained ruptured abdominal aortic aneurysm with hemodynamic stability.

PURPOSE: Food and Drug Administration-approved endografts are suitable for the elective repair of abdominal aortic aneurysms (AAAs) with favorable aneurysm anatomy. Our aim is to illustrate the feasibility and versatility of commercially available endografts for emergency AAA repair in hemodynamically stable AAA rupture. METHODS: From June 2001 to July 2002, five patients presented with severe abdominal pain and were diagnosed with contained rupture of an infrarenal AAA. In all cases, patients were deemed unfit to withstand conventional open repair by both the referring outside medical center as well as our center's team. All patients were hemodynamically stable on arrival at our medical center. Measurement and selection of endovascular devices were based on computed tomography (CT) scans performed emergently at the outside referring center. The required emergently procured endografts were obtained within 2 to 4.5 hours (mean, 3.1 hours) of presentation. Complex anatomy at the proximal and distal fixation zones or difficult access was present in every case. RESULTS: All patients survived endograft repair and had successful exclusion of their aneurysm sac on the basis of intraoperative arteriography and postoperative CT surveillance. All were discharged to home at baseline function within a mean of 6.8 days (range, 2-13 days). There were no deaths. There was one postoperative pulmonary embolism, one myocardial infarct, and one type 2 endoleak. Mean operative time and blood loss were 4.67 hours and 217 mL, respectively. At a mean follow-up of 18 months, CT scans showed stable or shrinking aneurysm sacs. CONCLUSIONS: In patients with contained ruptured AAAs who present with hemodynamic stability and comorbidities that preclude open surgery, commercially available endografts are a versatile treatment option even in the face of complicated aneurysm anatomy.

Aortic Aneurysm, Abdominal↗

PubMed2004

Decreased use of iliac extensions and reduced graft junctions with software-assisted centerline measurements in selection of endograft components for endovascular aneurysm repair.

OBJECTIVE: The purpose of this study was to determine the impact of using computerized software-assisted centerline measurements for extensions and graft junctions during the selection of endograft components for modular aortic endografts in endovascular repair of abdominal aortic aneurysms. METHODS: From April 1998 to December 2002, 289 modular aortic endografts were implanted at our institution. These included 248 grafts (prior to 2002, group 1) with components selected on the basis of manual caliper measurements from combined contrast computed tomography (CT) and marker-catheter arteriography data, and 41 grafts (2002, group 2) with components selected with the use of computerized software that allowed for centerline measurements on 3-dimensional reconstructions based on CT data. These 2 groups were compared for the number and type of extensions required per case. Seventeen other relevant variables were analyzed for their potential influence on selection of endograft components. These variables included age, gender, maximum aneurysm size, level of distal fixation, length and diameter at the fixation points, endograft manufacturer (make), and configuration. The significance of the observed differences was analyzed with a multivariate regression model, adjusting for potentially confounding preoperative measures. RESULTS: Multivariate analysis demonstrated that the number of right iliac extensions, left iliac extensions, total extensions, and total graft junctions was significantly reduced by the use of computerized software-assisted centerline measurements (group 2) compared with caliper measurements (group 1), independent of all other 17 preoperative variables. Notably, the mean number of required right iliac extensions was double in group 1 versus group 2. CONCLUSIONS: Centerline software-assisted measurements can significantly reduce the need for iliac extensions and, concomitantly, the number of required endograft junctions. On average, twice as many extensions were required for right iliac fixation when the manual caliper measurements were used compared with software-assisted measurements. These findings are highly relevant to issues of total endograft cost and long-term endograft integrity and focus attention on the tools that may need to be considered standards of care rather than optional for selection of endograft components.

Adult↗

PubMed2004

Midterm pivotal trial results of the Talent Low Profile System for repair of abdominal aortic aneurysm: analysis of complicated versus uncomplicated aortic necks.

OBJECTIVE: This study was undertaken to determine whether a complicated aortic neck is associated with unfavorable outcome after abdominal aortic aneurysm (AAA) endografting. METHODS: In a prospective pivotal clinical trial, 237 consecutive patients underwent implantation of the bifurcated Talent Low Profile System. Patients were divided into 2 groups, those with complicated aortic necks (short, <15 mm; very short, < or =10 mm; dilated, >28 mm; angulated, >45 degrees; calcified; and thrombus-lined) versus those with uncomplicated neck anatomy. Major outcome parameters included procedure time, operative blood loss, transfusion requirements, volume of contrast medium used during the implant procedure, endoleaks, migration, limb patency, AAA regression, conversion to open repair, morbidity, and mortality. Mean follow-up was 620.5 days. RESULTS: Overall, 32% of aortic necks were short, 19% were very short, 20% were dilated, 18% were calcified, 8.5% were thrombus-lined, and 19.9% were angulated. Thirty percent and 70% of patients, respectively, were stratified to the uncomplicated and complicated groups ( P < .01. Procedure time, operative blood loss, transfusions, volume of contrast medium used in the implant procedure, migration, endograft patency, AAA sac regression, conversion to open repair, and mortality were not significantly different in necks with complicated versus uncomplicated anatomy. At 21 months, sacs were regressing or stable in 98% (complicated) versus 96% (uncomplicated). Primary graft limb patency was 100% in both groups. The endoleak rate was 4.3% (complicated) versus 17% (uncomplicated) at 18 months, but this difference was not statistically significant. Adverse renal events, however, occurred in 27.5% (complicated) versus 13.6% (uncomplicated; P = .04). CONCLUSIONS: Complicated aortic neck is not associated with unfavorable outcome at midterm follow-up after AAA endografting. However, statistically more adverse renal events occur in patients with complicated neck anatomy.

Aorta↗

PubMed2003

VEGF-A and alphaVbeta3 integrin synergistically rescue angiogenesis via N-Ras and PI3-K signaling in human microvascular endothelial cells.

We recently showed that normal fibroblasts mediate capillary-like differentiation of human microvascular endothelial cells (HMVEC) in a 3-D angiogenesis model. Here, we show that a collaborative effect of VEGF-A and alphaVbeta3 integrin is critical in fibroblast-mediated angiogenesis because enhancement of both VEGF production by fibroblasts and beta3 integrin expression in HMVEC can rescue capillary-like endothelial differentiation under reduced serum conditions. To investigate the downstream signaling mechanisms, we compared N-Ras and Rho/Rac/Cdc42, as well as phosphatidylinositol 3-kinase (PI3-K) and Akt, for their involvement in the capillary-like network formation. The dominant-negative mutant of N-Ras (N-RasN17), but not the mutants of Rho/Rac/Cdc42, suppressed network formation. Overexpression of a constitutively active form of PI3-K rescued the network formation, which was inhibited by a dominant-negative >beta3 integrin; however, an active form of Akt failed to rescue the inhibition but induced a phenotypic change in HMVEC. Moreover, PI3-K is a downstream target of N-Ras because it could be co-immunoprecipitated with N-Ras, and its active form could rescue the inhibitory effect of N-Ras N17. Thus, our data indicate the existence of N-Ras- and PI3-K-dependent but Rho/Rac/Cdc42- and Akt-independent signaling mechanisms for the synergistic effect of VEGF-A and alphaVbeta3 on fibroblast-mediated microvascular network formation.

Blood Vessels↗

PubMed2003

A new endovascular approach to treatment of acute iliac limb occlusions of bifurcated aortic stent grafts with an exoskeleton.

Endovascular aneurysm repair continues to become increasingly popular. As the number of implanted endografts increases, complications will increase as well. We report a new approach to endovascular treatment in two patients with acute iliac limb occlusions of a bifurcated aortic endograft with an endoskeleton. Neither patient required femoral-femoral bypass grafting because of unilateral limb ischemia. We believe this is the optimal primary approach in patients with a bifurcated stent graft with an endoskeleton.

Acute Disease↗