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1.
J Vasc Surg ; 70(4): 1177-1191.e9, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31543165

RESUMO

OBJECTIVE: Randomized controlled trials have shown that drug-coated balloons (DCBs) provide superior results compared with percutaneous transluminal angioplasty (PTA) for the treatment of femoropopliteal artery disease. However, these trials have generally included short lesions, few occlusions, and small sample sizes. The present study was an individual-level pooled analysis of duplex ultrasonography (DUS) core laboratory-adjudicated and clinical events committee-adjudicated IN.PACT Admiral DCB subjects across two randomized controlled trials and two single-arm prospective studies to characterize the safety and effectiveness of DCB compared with PTA. METHODS: The subjects were treated with DCB (n = 926) or PTA (n = 143). The end points through 12 months included DUS core laboratory-adjudicated primary patency and clinically driven target lesion revascularization (CD-TLR) using Kaplan-Meier estimates and primary safety using proportions. A propensity-matched analysis of DCB (n = 466) to PTA (n = 136) was conducted to address confounders. RESULTS: At 12 months, DCB compared with PTA had significantly greater primary patency (88.8% vs 53.9%; P < .001), freedom from CD-TLR (94.3% vs 80.2%; P < .001), and better primary safety composite end point (94.1% vs 78.0%; P < .001). After propensity-matched analysis, DCB remained superior to PTA at 12 months for primary patency (90.5% vs 53.8%; P < .001), freedom from CD-TLR (96.9% vs 80.7%; P < .001), and the primary safety composite end point (96.3% vs 78.4%; P < .001). Across multiple prespecified subgroup analyses, including provisional stenting, DCB remained persistently superior to PTA. CONCLUSIONS: In the largest, DUS core laboratory-adjudicated, multiethnic, pooled DCB series to date, the IN.PACT Admiral DCB demonstrated significantly greater primary patency, freedom from CD-TLR, and better composite safety at 12 months compared with PTA.


Assuntos
Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Doença Arterial Periférica/terapia , Ultrassonografia Doppler Dupla , Dispositivos de Acesso Vascular , Idoso , Angioplastia com Balão/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Pontuação de Propensão , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
2.
Catheter Cardiovasc Interv ; 93(3): 511-513, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30489007

RESUMO

The aim of this article is to discuss the poor outcomes associated with critical limb ischemia (CLI) and the required knowledge needed for optimal care. There is an opportunity for the Society for Cardiovascular Angiography and Interventions (SCAI) to assist interventional cardiologists in enhancing CLI care through creation of training standards and development of educational content.


Assuntos
Cardiologistas , Competência Clínica , Procedimentos Endovasculares , Isquemia/terapia , Equipe de Assistência ao Paciente , Doença Arterial Periférica/terapia , Radiografia Intervencionista , Radiologistas , Cardiologistas/educação , Consenso , Estado Terminal , Currículo , Educação de Pós-Graduação em Medicina , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/educação , Humanos , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Radiografia Intervencionista/efeitos adversos , Radiologistas/educação , Resultado do Tratamento
3.
Catheter Cardiovasc Interv ; 90(4): 639-646, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28795488

RESUMO

OBJECTIVES: To propose a classification system for characterizing angiographic femoropopliteal artery restenosis patterns associated with common endovascular modalities. BACKGROUND: Peripheral artery disease is a worldwide issue affecting millions of people. Despite a myriad of endovascular technologies available to treat peripheral artery disease of the femoropopliteal arteries, restenosis remains a common failure mode. Characterizing common patterns of restenosis is important to discern the potential impact of baseline patient, lesion, and procedural characteristics, as well as treatment modalities on either the primary success or the failure patterns associated with restenosis. METHODS: Studies included in the analysis were from previous core laboratory-adjudicated femoropopliteal artery disease trials and registries reflecting a wide array of treatment modalities. RESULTS: From the subjects enrolled and analyzed, there were 403 total angiograms for analysis and adjudication. Target lesion revascularization images of the 32 validation cases were evaluated for index treated length, diameter stenosis, and lesion morphology characteristics. The following lesion types are proposed: Type 1 "Focal" pattern, which may be "Edge Proximal" or "Edge Distal" depending on location; a Type 2 "Multifocal" pattern which may also exhibit edge restenosis, but may also be "Edge Bilateral"; a Type 3 "Moderate" pattern and a Type 4 "Diffuse" pattern; and finally, a Type 5 "Occlusion". CONCLUSIONS: A classification system that enables healthcare professionals to anticipate and describe failures following the index procedure, thereby impacting the choice of options for retreatment, may facilitate consistency and standardization within the heterogeneous field of endovascular device treatments for the femoropopliteal artery.


Assuntos
Angiografia/métodos , Procedimentos Endovasculares/efeitos adversos , Artéria Femoral/diagnóstico por imagem , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Artéria Poplítea/diagnóstico por imagem , Consenso , Constrição Patológica , Humanos , Doença Arterial Periférica/classificação , Valor Preditivo dos Testes , Recidiva , Índice de Gravidade de Doença , Terminologia como Assunto , Resultado do Tratamento
4.
J Biol Chem ; 280(47): 39294-301, 2005 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-16159885

RESUMO

Elastic laminae are extracellular matrix constituents that not only contribute to the stability and elasticity of arteries but also play a role in regulating arterial morphogenesis and pathogenesis. We demonstrate here that an important function of arterial elastic laminae is to prevent monocyte adhesion, which is mediated by the inhibitory receptor signal regulatory protein (SIRP) alpha and Src homology 2 domain-containing protein-tyrosine phosphatase (SHP)-1. In a matrix-based arterial reconstruction model in vivo, elastic laminae were resistant to leukocyte adhesion and transmigration compared with the collagen-dominant arterial adventitia. The density of leukocytes within the elastic lamina-dominant media was about 58-70-fold lower than that within the adventitia from 1 to 30 days. An in vitro assay confirmed the inhibitory effect of elastic laminae on monocyte adhesion. The exposure of monocytes to elastic laminae induced activation of SIRP alpha, which in turn activated SHP-1. Elastic lamina degradation peptides extracted from arterial specimens could also activate SIRP alpha and SHP-1. The knockdown of SIRP alpha and SHP-1 by specific small interfering RNA diminished the inhibitory effect of elastic laminae, resulting in a significant increase in monocyte adhesion. These observations suggest that SIRP alpha and SHP-1 potentially mediate the inhibitory effect of elastic laminae on monocyte adhesion.


Assuntos
Artérias/fisiologia , Tecido Elástico/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Monócitos/fisiologia , Proteínas Tirosina Fosfatases/fisiologia , Receptores de Superfície Celular/fisiologia , Animais , Artérias/citologia , Adesão Celular/fisiologia , Tecido Elástico/citologia , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intracelular/genética , Leucócitos/fisiologia , Fosforilação , Proteína Fosfatase 1 , Proteína Tirosina Fosfatase não Receptora Tipo 6 , Proteínas Tirosina Fosfatases/genética , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular/genética
5.
Front Biosci ; 9: 2205-17, 2004 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-15353282

RESUMO

Biomaterials, including non-biodegradable and biodegradable polymers, and collagen and fibrin matrices, have been used in experimental and clinical arterial reconstruction. While these biomaterials exhibit various characteristics suitable for arterial reconstruction, the patency of biomaterial-based arterial substitutes remains problematic because of inflammation and thrombogenesis. Endothelial cell seeding of biomaterials has been proposed and used for reducing the thrombogenicity of biomaterials. However, difficulties in cell retention hamper the application of such an approach. Although autogenous vein grafts offer satisfactory results, not all patients possess veins available for arterial replacements. Thus, a critical issue in arterial reconstruction is developing arterial substitutes that are inflammation/thrombosis-resistant while possessing the characteristics of natural arteries. Here we show that allogenic vascular elastic laminae exhibit anti-inflammatory properties and may be considered a potential material for arterial reconstruction. In this article, we briefly review the composition, structure, and function of vascular elastic laminae, summarize recent discoveries on the role of elastic laminae in regulating leukocyte adhesion and vascular smooth muscle cell proliferation and migration, and discuss potential applications of allogenic elastic laminae to arterial reconstruction.


Assuntos
Materiais Biocompatíveis/química , Prótese Vascular , Angioplastia/métodos , Animais , Vasos Sanguíneos , Adesão Celular , Movimento Celular , Proliferação de Células , Elastina/biossíntese , Endotélio Vascular/citologia , Regulação da Expressão Gênica , Humanos , Inflamação , Leucócitos/química , Leucócitos/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Polímeros/química , Trombose
6.
Biomaterials ; 25(10): 1869-82, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-14738851

RESUMO

Synthetic polymers, including polytetrafluoroethylene and Dacron, and biomatrix proteins, including collagen and fibrin, have been used for the construction of vascular substitutes. However, these materials induce inflammatory reactions, contributing to thrombosis, smooth muscle cell (SMC) proliferation, and neointima formation, processes leading to the failure of vascular substitutes. Thus, a pressing issue in vascular reconstruction is to construct vascular substitutes with surface materials that are inflammation-resistant. Here, we demonstrate that the vascular elastic laminae exhibit such a property. Aortic specimens from donor rats were treated with 0.1M NaOH for various times, resulting in elastic lamina-collagen matrix scaffolds with and without the basal lamina. Matrix scaffolds were implanted into the host aorta with three different surface materials, including the elastic lamina, basal lamina, and adventitial collagen, and observed for leukocyte adhesion, endothelial migration, cell proliferation, and neointimal formation on these surfaces. It was found that the elastic lamina was associated with significantly lower leukocyte adhesion, BrdU incorporation, and neointima formation than the basal lamina and adventitial collagen, while the migration of endothelial cells was comparable on all three surfaces. The adventitial collagen matrix was associated with leukocyte infiltration from blood and subsequent SMC migration from the host aorta, whereas the elastic laminae were resistant to such processes. The morphology of the implanted elastic laminae appeared normal at all times. These observations suggest that the vascular elastic laminae exhibit inflammation-resistant properties and inhibit SMC mitogenic activities compared with collagen-containing matrices and may be considered a potential surface material for vascular reconstruction.


Assuntos
Aorta Abdominal/patologia , Aorta Abdominal/cirurgia , Prótese Vascular , Movimento Celular , Colágeno Tipo VI/metabolismo , Túnica Íntima/crescimento & desenvolvimento , Túnica Íntima/patologia , Animais , Divisão Celular , Tecido Elástico/patologia , Tecido Elástico/transplante , Células Endoteliais/patologia , Matriz Extracelular/metabolismo , Leucócitos/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Transplantes , Túnica Íntima/cirurgia
7.
Am J Physiol Heart Circ Physiol ; 285(3): H1081-90, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12738619

RESUMO

Blood vessels are subject to fluid shear stress, a hemodynamic factor that inhibits the mitogenic activities of vascular cells. The presence of nonuniform shear stress has been shown to exert graded suppression of cell proliferation and induces the formation of cell density gradients, which in turn regulate the direction of smooth muscle cell (SMC) migration and alignment. Here, we investigated the role of platelet-derived growth factor (PDGF)-beta receptor and Src in the regulation of such processes. In experimental models with vascular polymer implants, SMCs migrated from the vessel media into the neointima of the implant under defined fluid shear stress. In a nonuniform shear model, blood shear stress suppressed the expression of PDGF-beta receptor and the phosphorylation of Src in a shear level-dependent manner, resulting in the formation of mitogen gradients, which were consistent with the gradient of cell density as well as the alignment of SMCs. In contrast, uniform shear stress in a control model elicited an even influence on the activity of mitogenic molecules without modulating the uniformity of cell density and did not significantly influence the direction of SMC alignment. The suppression of the PDGF-beta receptor tyrosine kinase and Src with pharmacological substances diminished the gradients of mitogens and cell density and reduced the influence of nonuniform shear stress on SMC alignment. These observations suggest that PDGF-beta receptor and Src possibly serve as mediating factors in nonuniform shear-induced formation of cell density gradients and alignment of SMCs in the neointima of vascular polymer implants.


Assuntos
Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/fisiologia , Quinases da Família src/metabolismo , Animais , Becaplermina , Contagem de Células , Movimento Celular/fisiologia , Endotélio Vascular/fisiologia , Masculino , Modelos Cardiovasculares , Fosforilação , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Proto-Oncogênicas c-sis , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Estresse Mecânico
8.
Am J Physiol Heart Circ Physiol ; 285(3): H1072-80, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12730056

RESUMO

Smooth muscle cells (SMCs) are organized in various patterns in blood vessels. Whereas straight blood vessels mainly contain circumferentially aligned SMCs, curved blood vessels are composed of axially aligned SMCs in regions with vortex blood flow. The vortex flow-dependent feature of SMC alignment suggests a role for nonuniform fluid shear stress in regulating the pattern formation of SMCs. Here, we demonstrate that, in experimental models with vascular polymer implants designed for the observation of neointima formation and SMC migration under defined fluid shear stress, nonuniform shear stress possibly plays a role in regulating the direction of SMC migration and alignment in the neointima of the vascular implant. It was found that fluid shear stress inhibited cell growth, and the presence of nonuniform shear stress influenced the distribution of total cell density and induced the formation of cell density gradients, which in turn directed SMC migration and alignment. In contrast, uniform fluid shear stress in a control model influenced neither the distribution of total cell density nor the direction of SMC migration and alignment. In both the uniform and nonuniform shear models, the gradient of total cell density was consistent with the alignment of SMCs. These observations suggest that nonuniform shear stress may regulate the pattern formation of SMCs, possibly via mediating the gradient of cell density in the neointima of vascular polymer implants.


Assuntos
Modelos Cardiovasculares , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , Animais , Contagem de Células , Divisão Celular/fisiologia , Movimento Celular/fisiologia , Masculino , Polímeros , Próteses e Implantes , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/fisiologia , Estresse Mecânico
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