RESUMO
BACKGROUND: Patients with diabetes and diffuse infrageniculate arterial disease who present with chronic limb-threatening ischemia require an exact anatomical plan for revascularization. Advanced pedal duplex can be used to define possible routes for revascularization. In addition, pedal acceleration time (PAT) can predict the success or failure of both medical and surgical interventions. METHODS: A retrospective review of patients who were referred to our group for unilateral limb-threatening ischemia with isolated infrageniculate disease was conducted. Pedal duplex and PAT at the base of the wound was performed before and 1 week after intervention. The primary endpoint was limb salvage at 1 year. Revascularization was defined as direct or indirect based on the angiosome concept. RESULTS: Fifty-four patients meeting inclusion criteria presented over a 5-year period (toe wound, n = 42; heel wound, n = 8; both, n = 4). At 1 year, 10 (18.5%) had required below-knee amputation, whereas the remainder had healed/improved. Limb salvage was predicted by absence of ongoing smoking, absence of dialysis, and postprocedural PAT (class I/II). Limb salvage did not correlate with direct versus indirect revascularization. CONCLUSIONS: Advanced lower-extremity duplex in conjunction with determining PAT at the area of concern is a useful technique for mapping the vasculature and identifying targets for revascularization in patients with diffuse infrageniculate disease. Target artery revascularization to the wound bed resulting in a PAT less than 180 msec is predictive of limb salvage, regardless of whether perfusion is direct or indirect.
Assuntos
Pé Diabético , Salvamento de Membro , Ultrassonografia Doppler Dupla , Humanos , Estudos Retrospectivos , Masculino , Pé Diabético/cirurgia , Feminino , Salvamento de Membro/métodos , Idoso , Pessoa de Meia-Idade , Extremidade Inferior/irrigação sanguínea , Amputação Cirúrgica , Idoso de 80 Anos ou mais , Fatores de TempoRESUMO
BACKGROUND: In the setting of Peripheral Arterial Disease (PAD), pedal arch interrogation by ultrasound has not been well described. Patients with noncompressible vessels and/or open wounds of the foot may preclude the use of ankle-brachial indices, toe pressure measurements, or TcPO2, respectively. We propose that pedal artery interrogations with Pedal Acceleration Time (PAT) can be a predictor for limb salvage in patients with Chronic Limb-Threatening Ischemia (CLTI). METHODS: A retrospective review of a prospectively kept database was performed from 2018 to 2019. Patients with pending amputation due to severe infection (WIFI infection class 2 and 3) were excluded from the study. We identified 73 limbs with CLTI that fit the inclusion criteria. Data included WIFI classification, age, gender, cardiovascular risk factors, PAT, ABI, and TBI when reliable, were collected. PAT measurements were categorized into 4 classifications; 1 (40-120 msec), 2 (121-180 msec), 3 (181-224 msec), and 4 (Greater than 225 msec). Statistical analyses were performed. RESULTS: Seventy-three limbs with CLTI were included in our study. All patients underwent arterial revascularization with either percutaneous technique or arterial bypass. Limb salvage was achieved in 59 (81%) of the 73 limbs. All 59 limbs had a 2-classification improvement in their PAT following interventions. A total of 14 (19%) limbs without improvement in their PAT underwent above ankle level amputations. An improvement in PAT classes to class 1 or 2 is associated with limb salvage. CONCLUSIONS: Patients with noncompressible ankle pressures or nonobtainable toe pressures poses a challenge in the complete assessment of WIFI classification. Our group has shown that PAT can be used in the scoring system for severity of ischemia in conjunction with current WIFI classification. Our data suggests that limb salvage correlates with post procedure PAT in category 1 and 2. Therefore we propose that PAT be added as part of the WIFI classification.
Assuntos
Procedimentos Endovasculares , Pé/irrigação sanguínea , Claudicação Intermitente/diagnóstico por imagem , Claudicação Intermitente/cirurgia , Salvamento de Membro , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/cirurgia , Ultrassonografia Doppler em Cores , Ultrassonografia Doppler de Pulso , Enxerto Vascular , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Velocidade do Fluxo Sanguíneo , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Claudicação Intermitente/fisiopatologia , Salvamento de Membro/efeitos adversos , Masculino , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Enxerto Vascular/efeitos adversosRESUMO
BACKGROUND: Arterial duplex ultrasound (DUS) and ankle-brachial indices (ABIs) are accepted methods for assessing lower limb arterial perfusion. However, in a significant number of diabetic patients, medial wall calcification often precludes an ABI measurement. Direct, noninvasive duplex imaging of the pedal arch in the setting of peripheral arterial disease (PAD) has not been well evaluated. Although plantar arch interrogation is new to vascular ultrasound, imaging the plantar arteries appears to be a reliable angiographic technique for critical limb ischemia. We sought to define the utility of Plantar Acceleration Time as a surrogate for ABIs. METHODS: Patients undergoing DUS including Plantar Acceleration Time for suspicion of PAD were retrospectively reviewed in a prospective database over a 1-year period. Two hundred fifty nondiabetic patients (499 limbs) with documented ABI were studied. Plantar Acceleration Time was calculated (milliseconds [msec]) in each limb in the lateral plantar artery. Statistical analyses were performed using linear regression and analysis of variance testing using Microsoft Excel database (version 2016; Microsoft Corp, Redmond, WA). Patients were then grouped into 4 classes based on their clinical symptoms and ABI. Plantar Acceleration Time was similarly grouped into 4 distinct classes and correlated with the clinical and ABI classes. RESULTS: Plantar Acceleration Time correlated significantly with ABI (P < 0.001). There were significant differences in Plantar Acceleration Times between each class based on ABI and clinical presentation (P < 0.001 for each): Class 1 Plantar Acceleration Times 89.9 ± 15.5 msec; Class 2, 152.3 ± 28.4 msec; Class 3, 209.8 ± 25.5 msec, and Class 4, 270.2 ± 35.3 msec. CONCLUSIONS: Plantar Acceleration Time demonstrates a high correlation with ABI in patients with compressible arteries. Based on our results we propose the following categories of Plantar Acceleration Time, which appear to correlate with both clinical and ABI findings. ABI of 0.90-1.3 correlates with a Plantar Acceleration Time of 0-120 msec, ABI of 0.69-0.89 correlates with a Plantar Acceleration Time of 121-180 msec, ABI of 0.40-0.68 correlates with a Plantar Acceleration Time of 181-224 msec, and an ABI of 0.00-0.39 correlates with a Plantar Acceleration Time of greater than 225 msec. Further studies are ongoing to confirm whether Plantar Acceleration Time may be a suitable substitute to ABIs in patients with noncompressible arteries that preclude meaningful ABIs and gives more information regarding targeted angiosome perfusion to the foot.
Assuntos
Artérias/diagnóstico por imagem , Angiopatias Diabéticas/diagnóstico por imagem , Pé/irrigação sanguínea , Imagem de Perfusão/métodos , Doença Arterial Periférica/diagnóstico por imagem , Ultrassonografia Doppler , Aceleração , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Artérias/fisiopatologia , Velocidade do Fluxo Sanguíneo , Bases de Dados Factuais , Angiopatias Diabéticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de TempoRESUMO
A 26-year-old man presented with gunshot wound to the epigastrium. At surgery, he was hemodynamically stable and had a tense hematoma with thrill in zone 2 (right side) and porta triad. After liver injury was controlled, he underwent percutaneous stenting of a renal artery-vena cava fistula and the hepatic artery injury was followed. Historically, penetrating injury to zone 2 has mandated operative exploration. However, with the advent of endovascular options, in stable patients, catheter-based options offer a reasonable alternative with less risk of blood loss and possible nephrectomy. Renal artery stenting has been advocated for renal artery cava fistulas. The role of timing, hybrid operating suites, and traditional operative exposure will vary based on presentation and institutional capabilities.
Assuntos
Traumatismos Abdominais/cirurgia , Procedimentos Endovasculares/métodos , Hematoma/cirurgia , Fígado/cirurgia , Artéria Renal/cirurgia , Fístula Vascular/cirurgia , Veia Cava Inferior/cirurgia , Ferimentos por Arma de Fogo/cirurgia , Traumatismos Abdominais/complicações , Traumatismos Abdominais/diagnóstico por imagem , Adulto , Contusões , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/lesões , Humanos , Fígado/diagnóstico por imagem , Fígado/lesões , Vértebras Lombares/lesões , Masculino , Pâncreas/lesões , Veia Porta/diagnóstico por imagem , Veia Porta/lesões , Artéria Renal/diagnóstico por imagem , Artéria Renal/lesões , Veias Renais/diagnóstico por imagem , Veias Renais/lesões , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Stents , Tomografia Computadorizada por Raios X , Fístula Vascular/diagnóstico por imagem , Fístula Vascular/etiologia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/lesões , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/diagnóstico por imagemRESUMO
BACKGROUND: The management of blunt thoracic aortic injury (BTAI) has evolved radically in the last decade with changes in the processes of care and the introduction of thoracic endovascular aortic repair (TEVAR). These changes have wrought improved outcome, but the direct effect of TEVAR on outcome remains in question as previous studies have lacked vigorous risk adjustment and long-term follow-up. To address these knowledge gaps, we compared the outcomes of TEVAR, open surgical repair, and nonoperative management for BTAI. METHODS: Eight verified trauma centers recruited from the Western Trauma Association Multicenter Study Group retrospectively studied all patients with BTAI admitted between January 1, 2006, and June 30, 2016. Data included demographics, comorbidities, admitting physiology, injury severity, in-hospital care, and outcome. RESULTS: We studied 316 patients with BTAI; 57 (18.0%) were in extremis and died before treatment. Of the 259 treated surgically, TEVAR was performed in 176 (68.0%), open in 28 (10.8%), hybrid in 4 (1.5%), and nonoperative in 51 (19.7%). Thoracic endovascular aortic repair and open repair groups had similar Injury Severity Scale score, chest Abbreviated Injury Scale score, Trauma and Injury Severity Score, and probability of survival, but differed in median age (open: 28 [interquartile range {IQR}, 19-51]; TEVAR: 46 [IQR, 28-60]; p < 0.007), zone of aortic injury (p < 0.001), and grade of aortic injury (open: 6 [IQR, 4-6]; TEVAR: 2 [IQR, 2-4]; p < 0.001). The overall in-hospital mortality was 6.6% (TEVAR: 5.7%, open: 10.7%, nonoperative: 3.9%; p = 0.535). Of the 240 patients who survived to discharge, two died (one at 9 months and one at 8 years); both were managed with TEVAR, but the deaths were unrelated to the aortic procedure. Stent graft surveillance computed tomography scans were not obtained in 37.6%. CONCLUSIONS: The mortality of BTAI continues to decrease. Thoracic endovascular aortic repair, when anatomically suitable, should be the treatment of choice. Open repair remains necessary for more proximal injuries. Process improvement in computed tomography imaging in follow-up of TEVAR is warranted. LEVEL OF EVIDENCE: Therapeutic/care management, level III.
Assuntos
Aorta Torácica/lesões , Procedimentos Endovasculares/métodos , Avaliação de Resultados em Cuidados de Saúde , Traumatismos Torácicos/cirurgia , Centros de Traumatologia/normas , Lesões do Sistema Vascular/cirurgia , Ferimentos não Penetrantes/cirurgia , Adulto , Idoso , Aorta Torácica/diagnóstico por imagem , Aortografia , Prótese Vascular , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Taxa de Sobrevida/tendências , Traumatismos Torácicos/diagnóstico , Traumatismos Torácicos/mortalidade , Procedimentos Cirúrgicos Torácicos/métodos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Estados Unidos/epidemiologia , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/mortalidade , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/mortalidadeRESUMO
Both surgical and endovascular grafts have the rare risk of late secondary infection. Treatment varies based on the clinical setting, but in general the recommendations are that infected endografts be removed and reconstruction performed. In the abdominal aorta this may vary from homograft or other impregnated grafts to excision and extra-anatomic bypass. We discuss an unusual case which we believe serves as a useful review of this still debated area. A 58-year-old male presented with abdominal and back pain. Prior history was notable for human immunodeficiency virus positive status, pulmonary embolism (currently on Coumadin) and two years previously repair of a saccular infra-renal aneurysm with tube graft. The week prior to the onset of symptoms he suffered a noticeable scratch from his cat. Blood cultures were positive for pasturella multicoda. He was transferred to our institution and underwent resection and explantation, with homograft reconstruction. At one year he is alive and well.
RESUMO
BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has become the preferred intervention for managing traumatic thoracic aortic injury. The literature suggests that TEVAR is associated with reduced mortality and paraplegia compared with open repair (OR). The lack of guidelines for reporting results and the paucity of patient follow-up make interpretation of the literature difficult. METHODS: A literature review of English language papers on thoracic aortic trauma published between 2005 and 2010 was performed. Papers were analyzed to determine how many commented on injury data known to affect outcome (age, hemodynamic stability, injury severity, degree of aortic injury, etc.). RESULTS: Sixty-two retrospective reviews and six meta-analysis papers were identified. Of the review papers, only 6.4% described aortic anatomy using standard criteria, only 25.8% reported the degree of aortic injury, only 19.4% defined early or emergent intervention, only 32.3% provided details regarding hemodynamic stability, and only 56.5% described injury severity by Injury Severity Score. In a subset analysis of papers containing trauma relevant data, comparing TEVAR with OR, the TEVAR population was older, whereas the OR group was more often unstable. TEVAR had a significantly lower mortality, a trend to reduction in paralysis, but a significantly increased stroke rate. Follow-up was minimal in both groups. CONCLUSION: The lack of reporting guidelines coupled with a paucity of follow-up data weakens any recommendation regarding the optimal choice of intervention. To address these deficiencies, we recommend reporting guidelines specific to the trauma population that will allow better risk adjustment and improve the quality of the evidence base.
Assuntos
Aorta Torácica/lesões , Ruptura Aórtica/cirurgia , Procedimentos Endovasculares , Procedimentos Cirúrgicos Torácicos , Adulto , Aorta Torácica/cirurgia , Ruptura Aórtica/etiologia , Humanos , Escala de Gravidade do Ferimento , Metanálise como Assunto , Publicações Periódicas como Assunto/normas , Guias de Prática Clínica como Assunto , Resultado do TratamentoRESUMO
A patient with concomitant rupture of the thoracic aorta and right subclavian artery at its origin was managed with endovascular stents. Due to the patient's hypovolemic shock, kissing stents in the brachiocephalic artery were undersized, requiring repeat intervention with coils and cement. The technical and judgment aspects of this case are reviewed.
Assuntos
Aorta Torácica/lesões , Ruptura Aórtica/terapia , Procedimentos Endovasculares , Artéria Subclávia/lesões , Ruptura Aórtica/diagnóstico , Ruptura Aórtica/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Ruptura/diagnóstico , Ruptura/etiologia , Ruptura/terapia , StentsAssuntos
Embolia/etiologia , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/instrumentação , Isquemia/etiologia , Perna (Membro)/irrigação sanguínea , Doença Arterial Periférica/etiologia , Embolia/diagnóstico por imagem , Falha de Equipamento , Feminino , Humanos , Isquemia/diagnóstico por imagem , Perna (Membro)/diagnóstico por imagem , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Radiografia , Resultado do TratamentoRESUMO
Traumatic thoracic aortic injury remains a major cause of death following motor vehicle accidents. Endovascular approaches have begun to supersede open repair, offering the hope of reduced morbidity and mortality. The available endovascular technology is associated with specific anatomic considerations and complications. This paper will review the current status of endovascular management of traumatic thoracic aortic injuries.
RESUMO
Vascular smooth muscle cells (SMC) may be directly exposed to blood flow after an endothelial-denuding injury. It is not known whether direct exposure of SMC to shear stress reduces SMC turnover and contributes to the low rate of restenosis after most vascular interventions. This study examines if laminar shear stress inhibits SMC proliferation or stimulates apoptosis. Bovine aortic SMC were exposed to arterial magnitudes of laminar shear stress (11 dynes/cm(2)) for up to 24 h and compared to control SMC (0 dynes/cm(2)). SMC density was assessed by cell counting, DNA synthesis by (3)[H]-thymidine incorporation, and apoptosis by TUNEL staining. Akt, caspase, bax, and bcl-2 phosphorylation were assessed by Western blotting; caspase activity was also measured with an in vitro assay. Analysis of variance was used to compare groups. SMC exposed to laminar shear stress had a 38% decrease in cell number (n = 4, P = 0.03), 54% reduction in (3)[H]-thymidine incorporation (n = 3, P = 0.003), and 15-fold increase in TUNEL staining (n = 4, P < 0.0001). Akt phosphorylation was reduced by 67% (n = 3, P < 0.0001), whereas bax/bcl-2 phosphorylation was increased by 1.8-fold (n = 3, P = 0.01). Caspase-3 activity was increased threefold (n = 5, P = 0.03). Pretreatment of cells with ZVAD-fmk or wortmannin resulted in 42% increased cell retention (n = 3, P < 0.01) and a fourfold increase in apoptosis (n = 3, P < 0.04), respectively. Cells transduced with constitutively-active Akt had twofold decreased apoptosis (n = 3, P < 0.002). SMC exposed to laminar shear stress have decreased proliferation and increased apoptosis, mediated by the Akt pathway. These results suggest that augmentation of SMC apoptosis may be an alternative strategy to inhibit restenosis after vascular injury.
Assuntos
Apoptose/fisiologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Animais , Bovinos , Proliferação de Células , Células Cultivadas , Hemodinâmica , Humanos , Marcação In Situ das Extremidades Cortadas , Miócitos de Músculo Liso/citologia , Proteínas Proto-Oncogênicas c-akt/genética , Resistência ao Cisalhamento , Estresse MecânicoRESUMO
BACKGROUND: Cancer of unknown primary (CUP) origin is a very aggressive disease with a poor prognosis. Most of the literature reports of CUP are generated from tertiary cancer centers. METHODS: A retrospective chart review of all patients with a diagnosis of CUP was performed between January 1995 and January 2005. Age, gender, diagnostic evaluation, histologic diagnosis, location of metastases, treatment, and survival were recorded. RESULTS: Ninety-one patients met the inclusion criteria. The pathologic diagnoses included adenocarcinoma (42.8%), undifferentiated carcinoma (34.5%), squamous cell carcinoma (9.8%), neuroendocrine cancer (6.5%), sarcoma (3.2%), and nonspecific malignant neoplasm (3.2%). The overall mean survival was 9.2 months (95% confidence interval, 6.1-12.4 mo), and for squamous cell carcinoma was 26.9 months (standard error, 5.7; P = .007). CONCLUSIONS: CUP encompasses a variety of different pathologic entities with an overall dismal 5-year survival. Nonetheless, squamous cell and neuroendocrine CUP are associated with a significantly better early prognosis than the other malignancies.
Assuntos
Neoplasias Primárias Desconhecidas/epidemiologia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Carcinoma/secundário , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/secundário , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Feminino , Neoplasias de Cabeça e Pescoço/secundário , Hospitais Comunitários , Hospitais de Ensino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/mortalidade , Prognóstico , Estudos RetrospectivosRESUMO
Vascular smooth muscle cells exhibit varied responses after vessel injury and surgical interventions, including phenotypic switching, migration, proliferation, protein synthesis, and apoptosis. Although the source of the smooth muscle cells that accumulate in the vascular wall is controversial, possibly reflecting migration from the adventitia, from the circulating blood, or in situ differentiation, the intracellular signal transduction pathways that control these processes are being defined. Some of these pathways include the Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, Rho, death receptor-caspase, and nitric oxide pathways. Signal transduction pathways provide amplification, redundancy, and control points within the cell and culminate in biologic responses. We review some of the signaling pathways activated within smooth muscle cells that contribute to smooth muscle cell heterogeneity and development of pathology such as restenosis and neointimal hyperplasia.
Assuntos
Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Transdução de Sinais , Procedimentos Cirúrgicos Vasculares , Animais , Apoptose , Células da Medula Óssea/metabolismo , Diferenciação Celular , Movimento Celular , Proliferação de Células , Constrição Patológica/metabolismo , Constrição Patológica/patologia , Matriz Extracelular/metabolismo , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Músculo Liso Vascular/lesões , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Músculo Liso Vascular/cirurgia , Miócitos de Músculo Liso/patologia , Fenótipo , Proteínas Quinases/metabolismo , Células-Tronco/metabolismo , Procedimentos Cirúrgicos Vasculares/efeitos adversosRESUMO
Both neointimal hyperplasia and inward remodeling contribute to restenosis and lumen loss. Nogo-B has been recently described as an inhibitor of vascular injury and neointimal hyperplasia. To determine whether Nogo-B expression may be a mediator of inward remodeling, we examine the localization of expression of Nogo-B in an in vivo model that examines both neointimal hyperplasia and inward remodeling. The rabbit carotid artery was subjected to balloon injury, outflow branch ligation to reduce flow, or both balloon injury and reduction in flow. In balloon injury-induced neointimal hyperplasia Nogo-B expression was reduced in the intima and media but stimulated in the adventitia. In low flow-induced inward remodeling medial Nogo-B expression was not reduced and adventitial Nogo-B expression was not stimulated. Low flow significantly augmented balloon injury-induced neointimal hyperplasia and was accompanied by reduced intimal and medial Nogo-B expression, and increased adventitial Nogo-B expression in both smooth muscle cells and macrophages. Low flow-induced inward remodeling is not associated with changes in medial Nogo-B expression and is distinct from injury-induced neointimal hyperplasia. Pharmacological strategies to inhibit neointimal hyperplasia and restenosis using normal flow models may only partially account for lumen loss and therefore may not accurately predict responses in patients with extensive outflow disease.
Assuntos
Artérias Carótidas/patologia , Estenose das Carótidas/patologia , Proteínas da Mielina/análise , Túnica Íntima/patologia , Túnica Média/patologia , Animais , Apoptose , Biomarcadores/análise , Velocidade do Fluxo Sanguíneo , Artérias Carótidas/química , Artérias Carótidas/fisiopatologia , Artérias Carótidas/cirurgia , Estenose das Carótidas/metabolismo , Estenose das Carótidas/fisiopatologia , Cateterismo , Proliferação de Células , Tecido Conjuntivo/metabolismo , Tecido Conjuntivo/patologia , Modelos Animais de Doenças , Hiperplasia , Ligadura , Masculino , Proteínas Nogo , Coelhos , Estresse Mecânico , Resistência à Tração , Túnica Íntima/química , Túnica Média/químicaRESUMO
OBJECTIVE: Nonlaminar shear stress stimulates smooth muscle cell (SMC) proliferation and migration in vivo, especially after an endothelial-denuding injury. To determine whether sustained shear stress directly stimulates SMC proliferation in vitro, the effect of orbital shear stress on SMC proliferation, phenotype, and extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation was examined. METHODS: Bovine SMCs were exposed to orbital shear stress (210 rpm) for up to 10 days, with and without the ERK1/2 upstream pathway inhibitor PD98059 (10 microM) or the p38 pathway inhibitor SB203580 (10 microM). Proliferation was directly counted and assessed with proliferation cell nuclear antigen. Western blotting was used to assess activation of SMC ERK1/2 and SMC phenotype markers. RESULTS: SMCs exposed to sustained orbital shear stress (10 days) had 75% increased proliferation after 10 days compared with static conditions. Expression of markers of the contractile phenotype (alpha-actin, calponin) was decreased, and markers of the synthetic phenotype (vimentin, beta-actin) were increased. ERK1/2 was phosphorylated in the presence of orbital shear stress, and orbital shear-stress-stimulated SMC proliferation was inhibited in the presence of PD98059 but sustained in the presence of SB203580. Orbital shear-stress-induced changes in SMC phenotype were also inhibited in the presence of PD98059. CONCLUSION: Orbital shear stress directly stimulates SMC proliferation in long-term culture in vitro and is mediated, at least partially, by the ERK1/2 pathway. The ERK1/2 pathway may also mediate the orbital shear-stress-stimulated switch from SMC contractile to synthetic phenotype. These results suggest that shear-stress-stimulated SMC proliferation after vascular injury is mediated by a pathway amenable to pharmacologic manipulation.
Assuntos
Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/patologia , Animais , Biomarcadores/metabolismo , Bovinos , Proliferação de Células , Células Cultivadas , Técnicas In Vitro , Músculo Liso Vascular/fisiologia , Miócitos de Músculo Liso/fisiologia , Fosforilação , Probabilidade , Sensibilidade e Especificidade , Transdução de Sinais , Estresse MecânicoRESUMO
BACKGROUND: The incidence of vascular disease increases with age. Because atherosclerosis and neointimal hyperplasia colocalize in areas of disturbed shear stress, the effects of orbital shear stress (SS) on endothelial cell proliferation, protein kinase B (Akt) activation, and functional activity were analyzed using a senescence model. METHODS: Early- (p3 to 7) and late- (p28 to 32) passage bovine aortic endothelial cells were exposed to orbital SS (210 rpm) or static conditions (0 to 5 days). Cell proliferation was directly counted and confirmed with proliferating cell nuclear antigen reactivity. Phosphorylated and total Akt were assessed with Western blotting. Endothelial cell-induced smooth muscle cell migration was assessed with a Boyden chamber. RESULTS: Late-passage endothelial cells demonstrated no increase in orbital SS stimulated proliferation compared with early-passage cells (P = .42). Late-passage endothelial cells demonstrated decreased Akt phosphorylation in response to SS compared with early passage cells (n = 6, P = .01). Late-passage cells induced 26% less smooth muscle cell migration than early-passage cells (n = 3, P = .03). CONCLUSIONS: Late-passage endothelial cells demonstrate decreased proliferation, Akt phosphorylation, and secretion of smooth muscle cell chemoattractants in response to orbital SS compared with early passage cells. These results suggest that late-passage endothelial cells respond to SS differently than early-passage cells and confirm the utility of the in vitro senescence model.
Assuntos
Endotélio Vascular , Resistência ao Cisalhamento , Envelhecimento/fisiologia , Animais , Aorta/citologia , Apoptose/fisiologia , Western Blotting , Bovinos , Contagem de Células , Divisão Celular/fisiologia , Proliferação de Células , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Técnicas In Vitro , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , Fosforilação , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Estresse Mecânico , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Elderly patients are a rapidly expanding segment of the population. Recent studies suggest that octogenarians have mortality and morbidity after carotid endarterectomy (CEA) similar to that in their younger cohort. Outcomes of CEA performed in nonagenarians have not been commonly reported; this study seeks to determine the safety of CEA in nonagenarians in general practice. STUDY DESIGN: All patients in nonfederal Connecticut hospitals undergoing CEA between 1990 and 2002 were identified using the state discharge database (Chime Inc; ). RESULTS: A total of 14,679 procedures were performed during the 12 study years. Sixty-four patients were nonagenarians (0.4%). Perioperative mortality was higher among nonagenarians (3.1%) compared with younger patients, including the 2,379 octogenarians (0.6%; p = 0.008, chi-square; odds ratio = 9.1, p = 0.006). No statistically significant difference was noted in perioperative stroke rates between nonagenarians (3.1%) and octogenarians (1.2%; p = 0.35, chi-square; odds ratio 2.3, p = 0.28). Nonagenarians had longer hospital lengths of stay (7.3 days, p < 0.0001), intensive care unit lengths of stay (1.2 days, p = 0.0013), and greater hospital charges ($17,967 +/- $1,907, p < 0.0001) than younger patients. Nonagenarians underwent operative procedures more frequently in an emergent setting (22%) compared with octogenarians (11%, p < 0.001) and had a greater percentage of symptomatic presentations (stroke: 14% versus 11%, p = 0.04; transient ischemic attack: 8% versus 5%, p = 0.04, respectively). All perioperative deaths and strokes occurred in symptomatic nonagenarians (15% versus 0%, p = 0.038; 15% versus 0%, p = 0.038; respectively). CONCLUSIONS: Carotid endarterectomy is performed in nonagenarians, as a group, with greater rates of perioperative mortality and morbidity than in younger patients, including octogenarians. But nonagenarians have a greater rate of symptomatic and emergent presentations than younger patients, which may account for their increased mortality, morbidity, length of stay, and incurred charges. Asymptomatic nonagenarians have similar outcomes after carotid endarterectomy compared with younger patients, including octogenarians, with low rates of mortality and morbidity.
Assuntos
Doenças das Artérias Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Segurança , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Connecticut , Endarterectomia das Carótidas/mortalidade , Feminino , Humanos , Modelos Logísticos , Masculino , Fatores de Risco , Estatísticas não Paramétricas , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Because cardiac complications may predict long-term survival after carotid endarterectomy (CEA), this study evaluates contemporary outcome, including cardiac complications, after CEA. Patients in Connecticut hospitals undergoing CEA between 1991 and 2002 were identified using the state discharge database (Chime, Inc.;