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1.
J Vasc Surg ; 76(1): 88-95.e1, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35276270

RESUMO

OBJECTIVE: General anesthesia (GA) is associated with inherent risks that can be avoided by the use of lesser invasive anesthetic strategies. We hypothesize that examine and compare the use of local or regional anesthesia (LRA) to that of GA in patients undergoing thoracic endovascular aortic repair (TEVAR). METHODS: Patients undergoing TEVAR between 2010 and 2020 in the Vascular Quality Initiative were analyzed. Exclusion criteria included receipt of branched or physician-modified endografts and devices extending distally beyond zone 5. Patients were categorized as receiving LRA or GA. Center volume was reported by quartile according to annualized TEVAR volume, and operative outcomes were compared using appropriate frequentists tests. Univariable and multivariable regression models for anesthesia type and operative outcomes were created to compare unadjusted and adjusted rates of each outcome. Long-term survival was estimated using a Kaplan-Meier survival estimator, whereas adjusted survival analysis was performed using a Cox proportional hazards model. RESULTS: Of the 17,099 patients who underwent TEVAR, 7299 met the inclusion and exclusion criteria. Of these, 3.8% received LRA. There were no significant differences in the annual proportion of patients who received LRA from 2011 to 2020 (P = .49, χ2 test for trend). Only 18.8% of patients who received LRA were treated at the highest quartile volume centers. Patients who received LRA were older and more comorbid compared with those who received GA. There were no differences in in-hospital mortality (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.42-1.38; P = .44) or composite of any complication (OR, 0.79; 95% CI, 0.54-1.14; P = .22) between patients who received LRA compared with those who received GA. This also applied to patients presenting with rupture. Receipt of LRA was associated with lower odds of postoperative congestive heart failure (OR, 0.19; 95% CI, 0.01-0.89; P = .01) as well as decreased length of intensive care unit (OR, 0.54; 95% CI, 0.40-0.72; P < .01) and hospital length of stay (OR, 0.64; 95% CI, 0.46-0.84; P < .01). LRA was not associated with decreased long-term survival compared with GA (hazard ratio, 0.95; 95% CI, 0.72-1.25; P = .72). CONCLUSIONS: Despite a greater number of baseline comorbidities, patients undergoing TEVAR with LRA experienced shorter intensive care unit and postoperative lengths of stay, with similar operative outcomes and long-term survival compared with patients who received GA. Similar findings were found among the rupture cohort. LRA should be considered more frequently in select patients undergoing TEVAR.


Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Anestesia Geral/efeitos adversos , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Humanos , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
2.
J Vasc Surg ; 71(2): 408-422, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31327616

RESUMO

OBJECTIVE: Using a national data set, we sought to describe the population of patients and the nature and timing of reinterventions after thoracic endovascular aortic repair (TEVAR) by aortic disease as well as their impact on survival. METHODS: We evaluated the national data set for TEVAR in the Vascular Quality Initiative from 2010 to 2017. Student t-test and χ2 analysis were used to compare continuous and categorical variables in the reintervention and no reintervention groups, respectively. Freedom from reintervention and survival analysis was performed using Kaplan-Meier methods. RESULTS: A total of 7006 patients were evaluated: 51.2% thoracic aortic aneurysm, 33.5% type B dissection (TBD), 7.0% penetrating aortic ulcer, 6.7% trauma, and 1.6% intramural hematoma. Overall, 553 patients (7.9%) underwent at least one reintervention, with an in-hospital reintervention rate of 3.5%. Reinterventions were most commonly performed for TBD (11.5%), with reinterventions for other diseases occurring at lower rates: thoracic aortic aneurysm, 6.7%; intramural hematoma, 5.4%; penetrating aortic ulcer, 4.8%; and trauma, 1.8%. The most common cause of reintervention across all aortic diseases was type I endoleak. The most common long-term reinterventions were placement of endovascular stent graft (65%), other surgical treatments (15.9%), other endovascular treatment (13%), endovascular branch treatment (12.4%), surgical treatment with no device removal (11.0%), and surgical branch treatment (10.4%). Freedom from reintervention was decreased for TBD compared with other diseases (P < .001). There was no difference in survival comparing patients undergoing reinterventions and those without (P = .87). However, patients undergoing in-hospital reintervention trended toward increased mortality (P = .075). CONCLUSIONS: Whereas reinterventions were not rare after TEVAR, there was no difference in mortality between patients undergoing reintervention and those without. Patients undergoing TEVAR for TBD demonstrated the highest reintervention rate. This study highlights the importance of long-term follow-up to address disease-specific patterns of reintervention.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Procedimentos Endovasculares , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento , Estudos Retrospectivos , Taxa de Sobrevida
3.
J Vasc Surg ; 72(4): 1367-1374, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32178914

RESUMO

BACKGROUND: The characteristics of and indications for open abdominal aortic aneurysm (AAA) repair have evolved over time. We evaluated these trends through the experience at a tertiary care academic center. METHODS: A retrospective review was conducted for patients undergoing open AAA repair (inclusive of type IV thoracoabdominal aortic aneurysms) from 2005 to 2018 at an academic institution. Trends over time were evaluated using the Spearman test; Cox regression was used to determine predictors of mortality and to generate adjusted survival curves. RESULTS: There were 628 patients (71.5% male; 88.2% white) with a mean age of 70.5 ± 9.4 years who underwent open AAA repair with a mean aneurysm diameter of 6.2 ± 1.5 cm. The median length of stay was 10 days, and the median intensive care unit length of stay was 3 days. Urgent repair was undertaken in 21.1%; 22.3% were type IV thoracoabdominal aortic aneurysm repairs, and 9.9% were performed for explantation. Our series favored a retroperitoneal approach in the majority of cases (82.5%). The proximal clamp sites were supraceliac (46.1%), suprarenal (29.1%), and infrarenal (24.8%), with approximately a third requiring renal artery reimplantation. The average cross-clamp time was 25.5 ± 14.9 minutes; the mean renal ischemia time for supraceliac and suprarenal clamp sites was 28.4 ± 12.3 minutes and 23.5 ± 12.7 minutes, respectively. Postoperative renal dysfunction occurred in 19.6% of the overall cohort, with 6.2% requiring hemodialysis. Of those requiring postoperative hemodialysis, the majority (75%) received an urgent repair. The in-hospital mortality was 2.3% for elective cases vs 20.9% for urgent repair, and 29.8% of patients were discharged to rehabilitation, with an overall 30-day readmission rate of 7.9%. Over time, there were trends of increased aneurysm repair complexity, with decreasing infrarenal clamp sites, increasing supraceliac clamp sites, increasing proportion of explantations, and increasing need for bifurcated grafts. The acuity of aneurysm repair likewise changed, with the proportion of urgent repairs increasing over time, largely attributable to the rise in explantations. Clamp site influenced the frequency of perioperative complications. Urgent repairs and age at operation were associated with mortality, whereas mortality was not associated with need for explantation and clamp location. CONCLUSIONS: Aneurysm repair reflected increasing complexity over time, with the need for explantation among urgent repairs significantly on the rise. Urgency and clamp location independently predicted long-term mortality, even after adjustment for age. These findings underscore the changing landscape of open AAA repair in the current era.


Assuntos
Injúria Renal Aguda/epidemiologia , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Centros de Atenção Terciária/tendências , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Idoso , Aneurisma da Aorta Abdominal/mortalidade , Implante de Prótese Vascular/métodos , Implante de Prótese Vascular/estatística & dados numéricos , Implante de Prótese Vascular/tendências , Remoção de Dispositivo/estatística & dados numéricos , Remoção de Dispositivo/tendências , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Unidades de Terapia Intensiva/tendências , Tempo de Internação/estatística & dados numéricos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Stents/efeitos adversos , Centros de Atenção Terciária/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento
4.
Ann Vasc Surg ; 69: 217-223, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32497616

RESUMO

BACKGROUND: Definitive treatment of Paget-Schroetter syndrome (PSS) involves first rib resection (FRR), division of the anterior scalene muscle, and resection of the subclavius muscle. This is a single-institution experience with PSS, according to a treatment algorithm of preoperative venogram (accompanied by lysis and percutaneous mechanical thrombectomy as needed) followed by transaxillary FRR. In the later period of this experience, patients have often been discharged on aspirin only, with no plan for anticoagulation postoperatively. We sought to evaluate outcomes in light of this experience and these practice patterns. METHODS: Between 2007 and 2018, 125 transaxillary FRRs were performed in 123 patients. All patients presented with documented venous thrombosis, underwent diagnostic venography and-if indicated-lysis and percutaneous mechanical thrombectomy (VPT) before FRR. The patient was not offered FRR if the vein could not be crossed with a wire and patency was not re-established during percutaneous treatment. The experience was divided into early (before 2012, n = 50) and late (n = 75) periods. RESULTS: Mean patient age was 28.4 (12-64 years) years. Of the cohort, 33 were high-level competitive athletes, 13 presented with documented pulmonary embolism in addition to local symptoms, and 3 had a cervical rib fused to the first rib. Patients underwent FRR a median of 50 (4 days to 18 years) days after their initial symptoms, and a median of 22 (1 day to 9 months) days after their percutaneous intervention. Postoperative VPT was required in 23 patients and performed a median of 5 (1-137 days) days postoperatively; in 19 of these patients, postoperative VPT was required for postoperative re-thrombosis, whereas in 4 patients, postoperative VPT was planned before FRR due to vein stenosis or residual thrombus. All these patients were prescribed postoperative anticoagulation. No operative venous reconstruction or bypass was performed. Median follow-up time after FRR was 242 days; at last follow-up, 98.4% (123/125) of axillosubclavian veins were patent by duplex ultrasound (and all those patients were asymptomatic). Postoperative anticoagulation was less frequently prescribed in the late experience, with no difference in the rate of early re-thrombosis or follow-up patency. CONCLUSIONS: This experience demonstrates 98.4% patency at last follow-up with standard preoperative percutaneous venography and intervention, transaxillary FRR, and postoperative endovascular re-intervention only in cases with persistent symptoms, stenosis, or re-thrombosis. Patients presenting with both acute and chronic PSS did not require surgical venous reconstruction. In the later experience, patients frequently have not been anticoagulated postoperatively. Advantages of this algorithm include the following: (1) the cosmetic benefits of the transaxillary approach, (2) the preoperative assessment of the ability to recanalize the vein to determine which patients will benefit from surgery, (3) the capacity to use thrombolysis preoperatively, and (4) potential elimination of the risk and inconvenience of postoperative anticoagulation.


Assuntos
Anticoagulantes/administração & dosagem , Osteotomia , Cuidados Pós-Operatórios , Costelas/cirurgia , Trombose Venosa Profunda de Membros Superiores/cirurgia , Adolescente , Adulto , Anticoagulantes/efeitos adversos , Criança , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia/efeitos adversos , Philadelphia , Flebografia , Cuidados Pós-Operatórios/efeitos adversos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Trombectomia , Terapia Trombolítica , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa Profunda de Membros Superiores/diagnóstico por imagem , Trombose Venosa Profunda de Membros Superiores/fisiopatologia , Grau de Desobstrução Vascular , Adulto Jovem
5.
J Vasc Surg ; 67(4): 1082-1090, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29074115

RESUMO

OBJECTIVE: Published rates of reintervention after endovascular aneurysm repair (EVAR) range from 10% to 30%. We evaluated a single university center's experience with reinterventions in the context of Food and Drug Administration (FDA)-approved and trial devices. METHODS: Retrospective data collection was performed for patients who underwent infrarenal EVAR and required reintervention from 2000 to 2016. Trial devices included those used in FDA feasibility and pivotal trials. Time-to-event analysis was performed using Cox regression. Predictors of mortality and explantation were evaluated using logistic regression; survival analysis was performed using Kaplan-Meier methods. RESULTS: From 2000 to 2016, there were 1835 EVARs performed, and 137 patients (116 men; mean age, 72.2 ± 10.0 years) underwent reintervention with a mean aneurysm size of 5.9 ± 1.2 cm. The median follow-up was 5 years with an overall survival of 70.1%. The overall reintervention rate was 7.5%. FDA-approved devices had a reintervention rate of 6.4%, whereas trial devices had a rate of 14.4% (P < .001). For all devices, the most common cause of reintervention was type II endoleak (52.5%), followed by type I endoleak (18.2%), type III endoleak (9.5%), limb kink (7.3%), iliac occlusive disease (5.8%), endotension (1.5%), and other. The overall mean time to first reintervention was 2.3 ± 2.5 years, and univariate Cox regression identified male gender (hazard ratio, 1.91; 95% confidence interval [CI], 1.17-3.10; P = .010) and age at the time of EVAR (hazard ratio, 1.03; 95% CI, 1.01-1.05; P = .006) as risk factors for time to first reintervention. Among patients requiring reintervention, the mean number of reinterventions for trial devices was significantly greater than that for FDA-approved devices (2.18 vs 1.65; P = .01). Trial devices requiring reintervention had a nearly threefold higher odds for the need for more than two reinterventions (odds ratio, 2.88; 95% CI, 1.12-7.37; P = .034). Trial device, cause of reintervention, and type of reintervention were not predictive of the need for explantation or mortality, but the number of reinterventions was significantly associated with the need for explantation (odds ratio, 1.86; 95% CI, 1.17-2.96; P = .012). EVAR device and the need for explantation did not have an impact on mortality. CONCLUSIONS: Despite the rigorous nature of patient enrollment in clinical trials and the development of newer iterations of investigational devices, patients undergoing EVAR with trial devices are more likely to undergo a greater number of reinterventions than with FDA-approved devices. Although mortality and the need for explantation were not significantly associated with trial devices, the finding of a greater number of reinterventions highlights the need to properly inform patients willing to partake in investigational device trials.


Assuntos
Aneurisma Aórtico/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Ensaios Clínicos como Assunto , Aprovação de Equipamentos , Procedimentos Endovasculares/instrumentação , Complicações Pós-Operatórias/cirurgia , Reoperação , Stents , United States Food and Drug Administration , Idoso , Idoso de 80 Anos ou mais , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Distribuição de Qui-Quadrado , Remoção de Dispositivo , Intervalo Livre de Doença , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/mortalidade , Modelos de Riscos Proporcionais , Desenho de Prótese , Reoperação/efeitos adversos , Reoperação/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
7.
J Vasc Surg ; 64(4): 1093-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26372192

RESUMO

BACKGROUND: Despite promising therapeutic innovation over the last decade, peripheral arterial disease remains a prevalent morbidity, as many patients are still challenged with peripheral ischemia. We hypothesized that delivery of engineered stromal cell-derived factor 1-alpha (ESA) in an ischemic hind limb will yield significant improvement in perfusion. METHODS: Male rats underwent right femoral artery ligation, and animals were randomized to receive a 100 µL injection of saline (n = 9) or 6 µg/kg dosage of equal volume of ESA (n = 12) into the ipsilateral quadriceps muscle. Both groups of animals were also given an intraperitoneal injection of 40 µg/kg of granulocyte macrophage colony-stimulating factor (GMCSF). Perfusion was quantified using a laser Doppler imaging device preoperatively, and on postoperative days 0, 7, and 14. Immunohistochemistry was performed to quantify angiogenesis on day 14, and an mRNA profile was evaluated for angiogenic and inflammatory markers. RESULTS: Compared with the saline/GMCSF group at day 14, the ESA/GMCSF-injected animals had greater reperfusion ratios (Saline/GMCSF, 0.600 ± 0.140 vs ESA/GMCSF, 0.900 ± 0.181; group effect P = .006; time effect P < .0001; group×time effect P < .0001), elevated capillary density (10×; Saline/GMCSF, 6.40 ± 2.01 vs ESA/GMCSF, 18.55 ± 5.30; P < .01), and increased mRNA levels of vascular endothelial growth factor-A (Saline/GMCSF [n = 6], 0.298 ± 0.205 vs ESA/GMCSF [n = 8], 0.456 ± 0.139; P = .03). CONCLUSIONS: Delivery of ESA significantly improves perfusion in a rat model of peripheral arterial disease via improved neovasculogenesis, a finding which may prove beneficial in the treatment strategy for this debilitating disease.


Assuntos
Indutores da Angiogênese/farmacologia , Quimiocina CXCL12/farmacologia , Isquemia/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Engenharia de Proteínas , Músculo Quadríceps/irrigação sanguínea , Músculo Quadríceps/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Indutores da Angiogênese/administração & dosagem , Animais , Velocidade do Fluxo Sanguíneo , Quimiocina CXCL12/administração & dosagem , Modelos Animais de Doenças , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Membro Posterior , Mediadores da Inflamação/metabolismo , Injeções Intramusculares , Isquemia/genética , Isquemia/metabolismo , Isquemia/fisiopatologia , Masculino , Músculo Quadríceps/metabolismo , Ratos Wistar , Recuperação de Função Fisiológica , Fluxo Sanguíneo Regional , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Circ Res ; 114(4): 650-9, 2014 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-24366171

RESUMO

RATIONALE: After myocardial infarction, there is an inadequate blood supply to the myocardium, and the surrounding borderzone becomes hypocontractile. OBJECTIVE: To develop a clinically translatable therapy, we hypothesized that in a preclinical ovine model of myocardial infarction, the modified endothelial progenitor stem cell chemokine, engineered stromal cell-derived factor 1α analog (ESA), would induce endothelial progenitor stem cell chemotaxis, limit adverse ventricular remodeling, and preserve borderzone contractility. METHODS AND RESULTS: Thirty-six adult male Dorset sheep underwent permanent ligation of the left anterior descending coronary artery, inducing an anteroapical infarction, and were randomized to borderzone injection of saline (n=18) or ESA (n=18). Ventricular function, geometry, and regional strain were assessed using cardiac MRI and pressure-volume catheter transduction. Bone marrow was harvested for in vitro analysis, and myocardial biopsies were taken for mRNA, protein, and immunohistochemical analysis. ESA induced greater chemotaxis of endothelial progenitor stem cells compared with saline (P<0.01) and was equivalent to recombinant stromal cell-derived factor 1α (P=0.27). Analysis of mRNA expression and protein levels in ESA-treated animals revealed reduced matrix metalloproteinase 2 in the borderzone (P<0.05), with elevated levels of tissue inhibitor of matrix metalloproteinase 1 and elastin in the infarct (P<0.05), whereas immunohistochemical analysis of borderzone myocardium showed increased capillary and arteriolar density in the ESA group (P<0.01). Animals in the ESA treatment group also had significant reductions in infarct size (P<0.01), increased maximal principle strain in the borderzone (P<0.01), and a steeper slope of the end-systolic pressure-volume relationship (P=0.01). CONCLUSIONS: The novel, biomolecularly designed peptide ESA induces chemotaxis of endothelial progenitor stem cells, stimulates neovasculogenesis, limits infarct expansion, and preserves contractility in an ovine model of myocardial infarction.


Assuntos
Quimiocina CXCL12/farmacologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Animais , Quimiocina CXCL12/genética , Quimiotaxia/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Modelos Animais de Doenças , Desenho de Fármacos , Hemodinâmica/efeitos dos fármacos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Microcirculação/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Engenharia de Proteínas , Carneiro Doméstico , Pesquisa Translacional Biomédica , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia , Remodelação Ventricular/efeitos dos fármacos
9.
Circulation ; 128(11 Suppl 1): S95-104, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-24030426

RESUMO

BACKGROUND: Cell-mediated angiogenic therapy for ischemic heart disease has had disappointing results. The lack of clinical translatability may be secondary to cell death and systemic dispersion with cell injection. We propose a novel tissue-engineered therapy, whereby extracellular matrix scaffold seeded with endothelial progenitor cells (EPCs) can overcome these limitations using an environment in which the cells can thrive, enabling an insult-free myocardial cell delivery to normalize myocardial biomechanics. METHODS AND RESULTS: EPCs were isolated from the long bones of Wistar rat bone marrow. The cells were cultured for 7 days in media or seeded at a density of 5 × 10(6) cells/cm(2) on a collagen/vitronectin matrix. Seeded EPCs underwent ex vivo modification with stromal cell-derived factor-1α (100 ng/mL) to potentiate angiogenic properties and enhance paracrine qualities before construct formation. Scanning electron microscopy and confocal imaging confirmed EPC-matrix adhesion. In vitro vasculogenic potential was assessed by quantifying EPC cell migration and vascular differentiation. There was a marked increase in vasculogenesis in vitro as measured by angiogenesis assay (8 versus 0 vessels/hpf; P=0.004). The construct was then implanted onto ischemic myocardium in a rat model of acute myocardial infarction. Confocal microscopy demonstrated a significant migration of EPCs from the construct to the myocardium, suggesting a direct angiogenic effect. Myocardial biomechanical properties were uniaxially quantified by elastic modulus at 5% to 20% strain. Myocardial elasticity normalized after implant of our tissue-engineered construct (239 kPa versus normal=193, P=0.1; versus infarct=304 kPa, P=0.01). CONCLUSIONS: We demonstrate restoration and normalization of post-myocardial infarction ventricular biomechanics after therapy with an angiogenic tissue-engineered EPC construct.


Assuntos
Células Endoteliais/fisiologia , Células Endoteliais/transplante , Infarto do Miocárdio/cirurgia , Neovascularização Patológica/cirurgia , Engenharia Tecidual/métodos , Animais , Fenômenos Biomecânicos , Movimento Celular/fisiologia , Células Cultivadas , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Neovascularização Patológica/patologia , Neovascularização Patológica/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Wistar
10.
Circulation ; 128(11 Suppl 1): S59-68, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-24030422

RESUMO

BACKGROUND: Endothelial progenitor cells (EPCs) possess robust therapeutic angiogenic potential, yet may be limited in the capacity to develop into fully mature vasculature. This problem might be exacerbated by the absence of a neovascular foundation, namely pericytes, with simple EPC injection. We hypothesized that coculturing EPCs with smooth muscle cells (SMCs), components of the surrounding vascular wall, in a cell sheet will mimic the native spatial orientation and interaction between EPCs and SMCs to create a supratherapeutic angiogenic construct in a model of ischemic cardiomyopathy. METHODS AND RESULTS: Primary EPCs and SMCs were isolated from Wistar rats. Confluent SMCs topped with confluent EPCs were spontaneously detached from the Upcell dish to create an SMC-EPC bi-level cell sheet. A rodent ischemic cardiomyopathy model was created by ligating the left anterior descending coronary artery. Rats were then immediately divided into 3 groups: cell-sheet transplantation (n=14), cell injection (n=12), and no treatment (n=13). Cocultured EPCs and SMCs stimulated an abundant release of multiple cytokines in vitro. Increased capillary density and improved blood perfusion in the borderzone elucidated the significant in vivo angiogenic potential of this technology. Most interestingly, however, cell fate-tracking experiments demonstrated that the cell-sheet EPCs and SMCs directly migrated into the myocardium and differentiated into elements of newly formed functional vasculature. The robust angiogenic effect of this cell sheet translated to enhanced ventricular function as demonstrated by echocardiography. CONCLUSIONS: Spatially arranged EPC-SMC bi-level cell-sheet technology facilitated the natural interaction between EPCs and SMCs, thereby creating structurally mature, functional microvasculature in a rodent ischemic cardiomyopathy model, leading to improved myocardial function.


Assuntos
Endotélio Vascular/fisiologia , Isquemia Miocárdica/patologia , Miócitos de Músculo Liso/fisiologia , Neovascularização Patológica/patologia , Células-Tronco/fisiologia , Animais , Técnicas de Cocultura , Endotélio Vascular/patologia , Feminino , Humanos , Masculino , Ratos , Ratos Wistar , Células-Tronco/patologia , Fatores de Tempo
11.
J Biomech Eng ; 136(8)2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24860865

RESUMO

Ischemic heart disease is a major health problem worldwide, and current therapies fail to address microrevascularization. Previously, our group demonstrated that the sustained release of novel engineered stromal cell-derived factor 1-a analogue (ESA) limits infarct spreading, collagen deposition, improves cardiac function by promoting angiogenesis in the region surrounding the infarct, and restores the tensile properties of infarcted myocardium. In this study, using a well-established rat model of ischemic cardiomyopathy, we describe a novel and innovative method for analyzing the viscoelastic properties of infarcted myocardium. Our results demonstrate that, compared with a saline control group, animals treated with ESA have significantly improved myocardial relaxation rates, while reducing the transition strain, leading to restoration of left ventricular mechanics.


Assuntos
Quimiocina CXCL12/genética , Quimiocina CXCL12/farmacologia , Elasticidade/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Engenharia de Proteínas , Animais , Quimiocina CXCL12/administração & dosagem , Injeções , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos Wistar , Viscosidade/efeitos dos fármacos
12.
J Card Surg ; 28(6): 770-5, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24118109

RESUMO

BACKGROUND: Continuous flow left ventricular assist devices (CF LVAD) are being implanted with increasing frequency for end-stage heart failure. At the time of LVAD implant, a large proportion of patients have pulmonary hypertension, right ventricular (RV) dysfunction, and tricuspid regurgitation (TR). RV dysfunction and TR can exacerbate renal dysfunction, hepatic dysfunction, coagulopathy, edema, and even prohibit isolated LVAD implant. Repairing TR mandates increased cardiopulmonary bypass time and bicaval cannulation, which should be reserved for the time of orthotopic heart transplantation. We hypothesized that CF LVAD implant would improve pulmonary artery pressures, enhance RV function, and minimize TR, obviating need for surgical tricuspid repair. METHODS: One hundred fourteen continuous flow LVADs implanted from 2005 through 2011 at a single center, with medical management of functional TR, were retrospectively analyzed. Pulmonary artery pressures were measured immediately prior to and following LVAD implant. RV function and TR were graded according to standard echocardiographic criteria, prior to, immediately following, and long-term following LVAD. RESULTS: There was a significant improvement in post-VAD mean pulmonary arterial pressures (26.6 ± 4.9 vs. 30.2 ± 7.4 mmHg, p = 0.008) with equivalent loading pressures (CVP = 12.0 ± 4.0 vs. 12.1 ± 5.1 p = NS). RV function significantly improved, as noted by right ventricular stroke work index (7.04 ± 2.60 vs. 6.05 ± 2.54, p = 0.02). There was an immediate improvement in TR grade and RV function following LVAD implant, which was sustained long term. CONCLUSION: Continuous flow LVAD implant improves pulmonary hypertension, RV function, and tricuspid regurgitation. TR may be managed nonoperatively during CF LVAD implant.


Assuntos
Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Coração Auxiliar , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/terapia , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/terapia , Idoso , Pressão Arterial , Feminino , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Artéria Pulmonar/fisiopatologia , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Insuficiência da Valva Tricúspide/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular Direita
13.
Semin Intervent Radiol ; 37(4): 382-388, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33041484

RESUMO

Since its inception in the 1990s, endovascular aortic repair has quickly replaced traditional open aortic repair (OAR) as the most common method for elective treatment of abdominal aortic aneurysms (AAA). After numerous iterations and failures of different endografts, the technology has undergone dramatic improvements with evidence pointing to this technology serving as a safe and durable modality, albeit with the requirement of routine surveillance. Not surprisingly, the ability to treat patients with AAAs with minimally invasive technology that could theoretically mitigate some of the risks associated with OAR, such as aortic cross clamping and significant blood loss, was also adopted in patients with ruptured AAAs and is now the preferred treatment method if anatomically feasible.

14.
Sci Adv ; 3(6): e1603078, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28630913

RESUMO

Coronary artery disease is one of the most common causes of death and disability, afflicting more than 15 million Americans. Although pharmacological advances and revascularization techniques have decreased mortality, many survivors will eventually succumb to heart failure secondary to the residual microvascular perfusion deficit that remains after revascularization. We present a novel system that rescues the myocardium from acute ischemia, using photosynthesis through intramyocardial delivery of the cyanobacterium Synechococcus elongatus. By using light rather than blood flow as a source of energy, photosynthetic therapy increases tissue oxygenation, maintains myocardial metabolism, and yields durable improvements in cardiac function during and after induction of ischemia. By circumventing blood flow entirely to provide tissue with oxygen and nutrients, this system has the potential to create a paradigm shift in the way ischemic heart disease is treated.


Assuntos
Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Processos Fototróficos , Animais , Terapia Biológica , Cianobactérias , Metabolismo Energético , Testes de Função Cardíaca , Hipóxia/metabolismo , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/terapia , Miócitos Cardíacos/metabolismo , Fotossíntese , Ratos
15.
Eur J Cardiothorac Surg ; 48(3): 400-6, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25653250

RESUMO

OBJECTIVES: The aim of this study was to evaluate late development of aortic insufficiency (AI) with continuous flow left ventricular assist device (CLVAD). Development of AI is an increasingly recognized important complication in CLVAD therapy, but there are still few reports about this topic. METHODS: We analysed data from 99 patients who underwent CLVAD implantation. De novo AI was defined as the development of mild or greater AI in patients with none or trace preoperative AI. Anatomic and functional correlates of de novo AI were investigated. RESULTS: Among the 17 patients with preoperative mild AI, no improvements were observed in mitral regurgitation or LV end-systolic dimension. Of the remaining 82 patients, de novo AI was identified in 43 patients (52%), on the most recent follow-up echocardiography, and did not influence survival nor improvement of LV geometry. Rate of freedom from de novo AI at 1 year after CLVAD implantation was 35.9%. Development of significantly greater AI was observed in patients without valve opening (AI grade 1.3 ± 1.0 vs 0.7 ± 0.9; P = 0.005). By multivariate Cox hazard model, smaller body surface area (BSA) [hazard ratio: 0.83 [95% confidence interval (CI): 0.72-0.97], P = 0.018], larger aortic root diameter (AOD) [hazard ratio: 1.11 (95% CI: 1.02-1.22), P = 0.012] and higher pulmonary artery systolic pressure (PASP) [hazard ratio: 1.24 (95% CI: 1.10-1.41), P < 0.001] were identified as the independent preoperative risk factors for de novo AI. In a subset of patients with speed adjustments, increase of CLVAD speed worsened AI and led to insufficient LV unloading in patients with aortic dilatation (AOD ≥ 3.5 cm). CONCLUSION: Any significant mortality difference related to preoperative or development of postimplant AI was not found. AI was associated with changes in LV size, and there appears to be an interaction between BSA, preoperative PASP, time since implant, aortic valve opening, aortic size and development of AI. Longitudinal clinical management in CLVAD patients, particularly in terms of CLVAD speed optimization, should include careful assessment.


Assuntos
Insuficiência da Valva Aórtica/etiologia , Coração Auxiliar/efeitos adversos , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/fisiopatologia , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/fisiopatologia , Pressão Propulsora Pulmonar/fisiologia , Estudos Retrospectivos , Fatores de Risco , Função Ventricular Esquerda
16.
Tissue Eng Part A ; 21(19-20): 2515-25, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26154752

RESUMO

There exists a substantial body of work describing cardiac support devices to mechanically support the left ventricle (LV); however, these devices lack biological effects. To remedy this, we implemented a cell sheet engineering approach utilizing chondrocytes, which in their natural environment produce a relatively elastic extracellular matrix (ECM) for a cushioning effect. Therefore, we hypothesized that a chondrocyte cell sheet applied to infarcted and borderzone myocardium will biologically enhance the ventricular ECM and increase elasticity to augment cardiac function in a model of ischemic cardiomyopathy (ICM). Primary articular cartilage chondrocytes of Wistar rats were isolated and cultured on temperature-responsive culture dishes to generate cell sheets. A rodent ICM model was created by ligating the left anterior descending coronary artery. Rats were divided into two groups: cell sheet transplantation (1.0 × 10(7) cells/dish) and no treatment. The cell sheet was placed onto the surface of the heart covering the infarct and borderzone areas. At 4 weeks following treatment, the decreased fibrotic extension and increased elastic microfiber networks in the infarct and borderzone areas correlated with this technology's potential to stimulate ECM formation. The enhanced ventricular elasticity was further confirmed by the axial stretch test, which revealed that the cell sheet tended to attenuate tensile modulus, a parameter of stiffness. This translated to increased wall thickness in the infarct area, decreased LV volume, wall stress, mass, and improvement of LV function. Thus, the chondrocyte cell sheet strengthens the ventricular biomechanical properties by inducing the formation of elastic microfiber networks in ICM, resulting in attenuated myocardial stiffness and improved myocardial function.


Assuntos
Condrócitos/citologia , Engenharia Tecidual/métodos , Animais , Western Blotting , Cardiomiopatias/metabolismo , Imuno-Histoquímica , Masculino , Ratos , Ratos Wistar
17.
Circ Heart Fail ; 7(4): 619-26, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24902740

RESUMO

BACKGROUND: Neuregulin-1ß (NRG) is a member of the epidermal growth factor family possessing a critical role in cardiomyocyte development and proliferation. Systemic administration of NRG demonstrated efficacy in cardiomyopathy animal models, leading to clinical trials using daily NRG infusions. This approach is hindered by requiring daily infusions and off-target exposure. Therefore, this study aimed to encapsulate NRG in a hydrogel to be directly delivered to the myocardium, accomplishing sustained localized NRG delivery. METHODS AND RESULTS: NRG was encapsulated in hydrogel, and release over 14 days was confirmed by ELISA in vitro. Sprague-Dawley rats were used for cardiomyocyte isolation. Cells were stimulated by PBS, NRG, hydrogel, or NRG-hydrogel (NRG-HG) and evaluated for proliferation. Cardiomyocytes demonstrated EdU (5-ethynyl-2'-deoxyuridine) and phosphorylated histone H3 positivity in the NRG-HG group only. For in vivo studies, 2-month-old mice (n=60) underwent left anterior descending coronary artery ligation and were randomized to the 4 treatment groups mentioned. Only NRG-HG-treated mice demonstrated phosphorylated histone H3 and Ki67 positivity along with decreased caspase-3 activity compared with all controls. NRG was detected in myocardium 6 days after injection without evidence of off-target exposure in NRG-HG animals. At 2 weeks, the NRG-HG group exhibited enhanced left ventricular ejection fraction, decreased left ventricular area, and augmented borderzone thickness. CONCLUSIONS: Targeted and sustained delivery of NRG directly to the myocardial borderzone augments cardiomyocyte mitotic activity, decreases apoptosis, and greatly enhances left ventricular function in a model of ischemic cardiomyopathy. This novel approach to NRG administration avoids off-target exposure and represents a clinically translatable strategy in myocardial regenerative therapeutics.


Assuntos
Bioengenharia/métodos , Cardiomiopatias/tratamento farmacológico , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Miócitos Cardíacos/patologia , Neuregulina-1/administração & dosagem , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Proliferação de Células , Células Cultivadas , Preparações de Ação Retardada , Modelos Animais de Doenças , Imuno-Histoquímica , Injeções , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Miocárdio , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley
18.
Ann Thorac Surg ; 96(5): 1603-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23932318

RESUMO

BACKGROUND: Both leaflet resection and neochordal construction are effective mitral repair techniques, but they may become incrementally time-consuming when using minimally invasive approaches. We have used a single-suture leaflet-remodeling technique of inverting the prolapsed or flail segment tissue into the left ventricle. This repair is straightforward, expeditious, and facilitates a minimally invasive approach. METHODS: Ninety-nine patients with degenerative mitral regurgitation (MR) underwent a minimally invasive single-suture repair of the mitral valve from May 2007 through December 2012. Preoperative and perioperative echocardiograms as well as patient outcomes were analyzed and compared with those obtained from patients undergoing minimally invasive mitral valve repair using quadrangular resection at the same institution during the same period. RESULTS: All 99 patients had a successful mitral repair through a sternal-sparing minimally invasive approach. Ninety-one of the 99 patients had zero MR on postoperative echocardiogram, and 8 of 99 had trace to mild MR. Patients in the nonresectional group had significantly shorter cardiopulmonary bypass and cross-clamp times compared with the quadrangular resection group (115.8 ± 41.7 minutes versus 144.9 ± 38.2 minutes; p < 0.001; 76.2 ± 28.1 minutes versus 112.6 ± 33.5 minutes; p < 0.001, respectively). The mean length of stay was 7.5 ± 3 days. All patients were discharged alive and free from clinical symptoms of MR. There have been no reoperations for recurrent MR on subsequent average follow-up of 1 year. CONCLUSIONS: An effective, highly efficient, and thus far durable single-suture mitral leaflet-remodeling technique facilitates minimally invasive repair of degenerative MR.


Assuntos
Insuficiência da Valva Mitral/cirurgia , Técnicas de Sutura , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos
19.
J Thorac Cardiovasc Surg ; 145(1): 278-84, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23244259

RESUMO

OBJECTIVE: The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell-derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction. METHODS: Male rats (n = 54) underwent either sham surgery (n = 17) with no coronary artery ligation or ligation of the left anterior descending artery (n = 37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n = 18) or ESA (6 µg/kg, n = 19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB. RESULTS: Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P = .0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P = .04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P = .05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P = .04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle. CONCLUSIONS: Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart.


Assuntos
Cardiotônicos/farmacologia , Quimiocina CXCL12/farmacologia , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/patologia , Função Ventricular/efeitos dos fármacos , Animais , Fenômenos Biomecânicos , Cardiotônicos/administração & dosagem , Cardiotônicos/síntese química , Quimiocina CXCL12/administração & dosagem , Quimiocina CXCL12/síntese química , Desenho Assistido por Computador , Modelos Animais de Doenças , Desenho de Fármacos , Injeções , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Volume Sistólico/efeitos dos fármacos , Resistência à Tração , Fatores de Tempo , Ultrassonografia , Remodelação Ventricular/efeitos dos fármacos
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