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1.
Ann Plast Surg ; 92(4S Suppl 2): S167-S171, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556668

RESUMO

BACKGROUND: Osteocutaneous fibula free flaps (FFFs) are a fundamental component of reconstructive surgery in the head and neck region, particularly after traumatic injuries or oncologic resections. Despite their utility, FFFs are associated with various postoperative complications, such as infection, flap failure, and donor site morbidity, impacting up to 54% of cases. This study aimed to investigate the influence of socioeconomic variables, with a particular focus on median household income (MHI), on the incidence of postoperative complications in FFF reconstruction for head and neck cancer. METHODS: A retrospective analysis of 80 patients who underwent FFF reconstruction for head and neck cancer at a single center from 2016 to 2022 was conducted. Demographic and patient characteristics, including race, MHI, insurance type, history of radiation therapy, and TNM (tumor, node, metastasis) cancer stage, were evaluated. Logistic regression, controlling for comorbidities, was used to assess the impact of MHI on 30-, 90-, and 180-day postoperative complications. RESULTS: The patient population was predominantly male (n = 51, 63.8%) and White (n = 63, 78.8%), with the majority falling within the $55,000 to $100,000 range of MHI (n = 51, 63.8%). Nearly half of the patients had received neoadjuvant radiation treatment (n = 39, 48.75%), and 36.25% (n = 29) presented with osteoradionecrosis. Logistic regression analysis revealed that the $55,000-$100,000 MHI group had significantly lower odds of developing complications in the 0- to 30-day postoperative period when compared with those in the <$55,000 group (odds ratio [OR], 0.440; 95% confidence interval [CI], 0.205-0.943; P = 0.035). This trend persisted in the 31- to 90-day period (OR, 0.136; 95% CI, 0.050-0.368; P < 0.001) and was also observed in the likelihood of flap takeback. In addition, the $100,000-$150,000 group had significantly lower odds of developing complications in the 31- to 90-day period (OR, 0.182; 95% CI, 0.035-0.940; P = 0.042). No significant difference was found in the >$150,000 group. CONCLUSIONS: Median household income is a significant determinant and potentially a more influential factor than neoadjuvant radiation in predicting postoperative complications after FFF reconstruction. Disparities in postoperative outcomes based on income highlight the need for substantial health care policy shifts and the development of targeted support strategies for patients with lower MHI.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Humanos , Masculino , Feminino , Estudos Retrospectivos , Disparidades Socioeconômicas em Saúde , Neoplasias de Cabeça e Pescoço/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
2.
Ann Plast Surg ; 92(4S Suppl 2): S161-S166, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556667

RESUMO

BACKGROUND: Tissue expansion has been widely used to reconstruct soft tissue defects following burn injuries in pediatric patients, allowing for satisfactory cosmetic and functional outcomes. Factors impacting the success of tissue expander (TE)-based reconstruction in these patients are poorly understood. Herein, we aim to determine the risk factors for postoperative complications following TE-based reconstruction in pediatric burn patients. METHODS: A retrospective review of pediatric patients who underwent TE placement for burn reconstruction from 2006 to 2019 was performed. Primary outcomes were major complications (TE explantation, extrusion, replacement, flap necrosis, unplanned reoperation, readmission) and wound complications (surgical site infection and wound dehiscence). Descriptive statistics were calculated. The association between primary outcomes, patient demographics, burn characteristics, and TE characteristics was assessed using the chi-squared, Fisher's exact, and Mann-Whitney U tests. RESULTS: Of 28 patients included in the study, the median [interquartile range (IQR)] age was 6.5 (3.3-11.8) years, with a follow-up of 12 (7-32) months. The majority were males [n = 20 (71%)], Black patients [n = 11 (39%)], and experienced burns due to flames [n = 78 (29%)]. Eleven (39%) patients experienced major complications, most commonly TE premature explantation [n = 6 (21%)]. Patients who experienced major complications, compared to those who did not, had a significantly greater median (IQR) % total body surface area (TBSA) [38 (27-52), 10 (5-19), P = 0.002] and number of TEs inserted [2 (2-3), 1 (1-2), P = 0.01]. Ten (36%) patients experienced wound complications, most commonly surgical site infection following TE placement [n = 6 (21%)]. Patients who experienced wound complications, compared to those who did not, had a significantly greater median (IQR) %TBSA [35 (18-45), 19 (13-24), P = 0.02]. CONCLUSION: Pediatric burn injuries involving greater than 30% TBSA and necessitating an increasing number of TEs were associated with worse postoperative complications following TE-based reconstruction.


Assuntos
Queimaduras , Dispositivos para Expansão de Tecidos , Masculino , Humanos , Criança , Feminino , Dispositivos para Expansão de Tecidos/efeitos adversos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/etiologia , Queimaduras/complicações , Expansão de Tecido/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
3.
Cleft Palate Craniofac J ; : 10556656241259883, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836317

RESUMO

OBJECTIVE: This study evaluates the geospatial distribution of cleft lip and/or cleft palate (CL/P) care in the United States, assesses disparities between families with and without one-hour proximity to CL/P care, and recommends interventions for improving access. DESIGN: We identified American Cleft Palate Craniofacial Association-approved CL/P teams and calculated a one-hour driving radius around each clinic. We then used census data to compare risk factors for developing cleft (i.e., incidence risk factors) and obstacles to care (i.e., access risk factors) between counties with and without one-hour proximity. RESULTS: We identified 187 CL/P teams in 45 states. Most were in the South (n = 60, 32.0%), though children in the Middle Atlantic had the greatest access to care. Alabama, Mississippi, Tennessee, and Kentucky had the least access. Children without access were 39% more likely to have gestational tobacco exposure, 8% more likely to have gestational obesity exposure, and 28% less likely to have health insurance (p < 0.01). Children without access in the South were 29% more likely to have a low birth weight and 46% more likely to be living below the poverty line (p < 0.01). Children with access were twice as likely to live in immigrant families and 7-times more likely to speak English as a second language. CONCLUSIONS: Pronounced disparities affect patients with and without one-hour access to CL/P care. Interventions should address care costs for patients living furthest without access and language barriers for patients with access that speak English as a second language.

4.
Cleft Palate Craniofac J ; : 10556656221135925, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36310432

RESUMO

OBJECTIVE: Determine if the ideal location of the construct in microtia reconstruction for hemifacial microsomia (HFM) can be more accurately derived from measurements on the cranium. DESIGN: High-resolution computerized tomography (CT) images were analyzed through craniometric linear relationships. SETTING: Our tertiary care institution from 2000 to 2021. PATIENTS/PARTICIPANTS: Patients diagnosed with HFM and microtia, who had high-resolution craniofacial CT scans, yielding 36 patients accounting for 44 CT scans. MAIN OUTCOME MEASURE(S): First, the integrity of the posterior cranial vault among HFM patients was determined. If proven to be unaffected, it could be used as a reference in the placement of the construct. Second, the position of the ear in relation to the cranium was assessed in healthy age-matched controls. Third, if proven to be useful, the concordance of these cranium-based relationships could be validated among our HFM cohort. RESULTS: The posterior cranial vault is unaffected in HFM (P > .001). Further, craniometric relationships between the tragus and the Foramen Magnum, as well as between the tragus and the posterior cranium, have been shown to be highly similar and equally precise in predicting tragus position in healthy controls (P > .001). These relationships held true across all age groups (P > .001), and importantly among HFM patients, where the mean absolute difference in predicted tragus position never surpassed 1.5 mm. CONCLUSIONS: Relationships between the tragus and the cranium may be used as an alternative to distorted facial anatomy or surgeon's experience to assist in pre-operative planning of construct placement in microtia reconstruction for HFM patients.

5.
J Craniofac Surg ; 30(7): 1999-2000, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31232988

RESUMO

Spontaneous osteogenesis of traumatic mandibular defects in the pediatric population remains a relatively rare phenomenon with only 2 patients reported in the literature. In the adult population, a low threshold exists for bone graft placement in the presence of small mandibular gaps, with no role for spontaneous osteogenesis in significant mandibular defects. The approach to traumatic mandibular defects in the pediatric population is not clearly described in the literature and the risks and benefits associated with donor site morbidity of bone graft harvest must be tempered by the possibility for potential spontaneous osteogenesis. The present study reports 1 such patient in whom a significant mandibular defect healed by means of rigid fixation of the defect and spontaneous osteogenesis, with no functional or esthetic sequelae at long-term follow-up. A review of the pertinent literature was performed, and the authors' approach is discussed. The authors propose that traumatic mandibular defects of < 3 cm in patients under the age of 10 years should be considered for treatment with rigid internal fixation alone and spontaneous osteogenesis.


Assuntos
Osteogênese , Transplante Ósseo , Criança , Feminino , Humanos , Mandíbula/cirurgia
6.
World J Surg ; 42(2): 376-383, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29110159

RESUMO

BACKGROUND: Errors in judgment during thyroidectomy can lead to recurrent laryngeal nerve injury and other complications. Despite the strong link between patient outcomes and intraoperative decision-making, methods to evaluate these complex skills are lacking. The purpose of this study was to develop objective metrics to evaluate advanced cognitive skills during thyroidectomy and to obtain validity evidence for them. METHODS: An interactive online learning platform was developed ( www.thinklikeasurgeon.com ). Trainees and surgeons from four institutions completed a 33-item assessment, developed based on a cognitive task analysis and expert Delphi consensus. Sixteen items required subjects to make annotations on still frames of thyroidectomy videos, and accuracy scores were calculated based on an algorithm derived from experts' responses ("visual concordance test," VCT). Seven items were short answer (SA), requiring users to type their answers, and scores were automatically calculated based on their similarity to a pre-populated repertoire of correct responses. Test-retest reliability, internal consistency, and correlation of scores with self-reported experience and training level (novice, intermediate, expert) were calculated. RESULTS: Twenty-eight subjects (10 endocrine surgeons and otolaryngologists, 18 trainees) participated. There was high test-retest reliability (intraclass correlation coefficient = 0.96; n = 10) and internal consistency (Cronbach's α = 0.93). The assessment demonstrated significant differences between novices, intermediates, and experts in total score (p < 0.01), VCT score (p < 0.01) and SA score (p < 0.01). There was high correlation between total case number and total score (ρ = 0.95, p < 0.01), between total case number and VCT score (ρ = 0.93, p < 0.01), and between total case number and SA score (ρ = 0.83, p < 0.01). CONCLUSION: This study describes the development of novel metrics and provides validity evidence for an interactive Web-based platform to objectively assess decision-making during thyroidectomy.


Assuntos
Tomada de Decisões Assistida por Computador , Técnicas de Apoio para a Decisão , Internet , Cirurgiões , Tireoidectomia/educação , Adulto , Competência Clínica , Tomada de Decisões , Feminino , Humanos , Masculino , Erros Médicos/prevenção & controle , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Tireoidectomia/métodos
7.
Plast Reconstr Surg Glob Open ; 10(1): e4050, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35083104

RESUMO

Syndactyly is one of the most common congenital hand malformations, involving an abnormal fusion of digits and with treatment varying according to its complexity. The internet has become a primary source of information for both families and patients with congenital hand anomalies. The purpose of this study was to evaluate both the readability and quality of available web content for syndactyly, using validated instruments. METHODS: Two independent reviewers conducted searches for "Syndactyly" using three of the largest online search engines: Bing, Google, and Yahoo. The top 10 websites for each search engine, along with any webpage within one click of the parent website, were analyzed. Readability was assessed using seven established quantitative tests. The quality of the web pages was analyzed using the Discern questionnaire and handbook. RESULTS: A total of 15 websites were included in the analysis. The average readability of all websites was equivalent to comprehension at a grade 11.3 level. The average Flesch reading ease score was 49.3 out of 100, which is considered difficult to read. Quality was assessed using Discern, a brief questionnaire consisting of 16 questions with five points attributed per question. The mean quality score using Discern was 33.3 points out of a maximum of 80 points. CONCLUSIONS: Online materials pertaining to the treatment of syndactyly far exceed the recommended sixth-grade reading level, and lack in terms of quality and comprehensiveness of information. Health care professionals should be cognizant of the paucity of available online information and provide patients with more appropriate resources.

8.
Plast Reconstr Surg Glob Open ; 10(11): e4649, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36415618

RESUMO

Facial vascularized composite allotransplantation (VCA) offers an added layer of complexity when compared to solid organ transplantation. VCAs must account for aesthetic variables such as skin tone and color. The goal of this study is to validate the Nix Color Sensor as a novel tool to be added to the plastic surgeon's armamentarium for evaluating skin color match of the donor and recipient. Methods: A prospective study of 100 individuals was conducted. All participants were photographed and scanned with the Nix Color Sensor. Sixty pairwise comparisons were randomly generated. Skin color analysis was performed using photographs and the Nix Color Sensor. Delta E2000 values were compared to mean evaluator ratings using a Spearman correlation analysis. Results: One hundred patients were included. A Spearman's correlation demonstrated a strong inverse correlation between Delta E2000 values and the mean evaluator ratings. The higher the mean evaluator rating for likeness, the lower the delta. A correlation coefficient of -0.850 demonstrates a statistically significant relationship (P < 0.01). Conclusions: When the Delta E2000 rises above 5 there is a significant drop in the mean evaluator ratings. As mean evaluator ratings of 5 and above would be considered adequate for face transplant amongst most plastic surgeons, an E2000 value of 5 or lower should be targeted when matching donors with recipients for face transplant. The Nix Color Sensor positively correlates to the plastic surgeon's perception of skin color and can serve as an adjunct in donor selection for facial VCAs.

9.
Plast Reconstr Surg Glob Open ; 10(8): e4486, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36032368

RESUMO

Background: Hemifacial microsomia (HFM) is one of the most common congenital craniofacial disorders. Among many other features, microtia is present in the large majority of these patients. However, mainly due to the unilateral hypoplastic anatomy, microtia reconstruction among this patient population remains a reconstructive challenge for plastic surgeons. Given that no clear standards exist, an evidence-based synthesis of the literature was devised. Methods: A systematic search of Pubmed, Medline, and Embase was carried out, in accordance with the PRISMA guidelines. Studies discussing surgical microtia reconstruction for HFM patients were retained. Qualitative data regarding study design, challenges addressed, specific recommendations, and their respective strengths/limitations were extracted from each. Retrieved recommendations were consolidated and assigned a level of evidence grade. Results: Although only 11 studies were included in this review, these provided 22 main recommendations regarding the eight HFM-specific challenges identified, which were of either grade C (n = 5) or D (n = 17). Included studies addressed construct location (n = 7), the low hairline (n = 6), soft tissue construct coverage (n = 6), earlobe reconstruction (n = 6), construct projection (n = 5), anomalies of the relevant neurovascular systems (n = 2), retroauricular construct coverage (n = 2), and sizing of the construct (n = 2). Conclusions: Given the many persisting reconstructive challenges regarding surgical microtia reconstruction for HFM patients, the authors present a comprehensive and evidence-based consolidation of recommendations specific to these challenges. The authors hope this systematic review can appropriately guide plastic surgeons and will ultimately improve care for this patient population.

10.
JPRAS Open ; 32: 116-121, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35368582

RESUMO

Arterialized venous flaps (AVFs) are an innovative option in hand reconstruction. Their exact vascular physiology and survival mechanisms remain unclear. We report on two hand reconstruction cases with AVFs. Indocyanine green laser angiography was used to assess vascular perfusion of the flaps. A notable change in flap perfusion was seen by 48 h post-operatively with normalization of shunting and progression to a diffuse perfusion pattern resembling traditional flaps. Flap survival was attributed to reversed shunting at the microvascular level occurring within the first 48 h post-operatively.

11.
Plast Reconstr Surg Glob Open ; 10(4): e4268, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35475286

RESUMO

Background: The intercanthal distance (ICD) is central to our perception of facial proportions, and it varies according to gender and ethnicity. Current standardized reference values do not reflect the diversity among patients. Therefore, the authors sought to provide an evidence-based and gender/ethnicity-specific reference when evaluating patients' ICD. Methods: As per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of PubMed, Medline, and Embase was carried out for studies reporting on the ICD. Demographics, study characteristics, and ICDs were extracted from included studies. ICD values were then pooled for each ethnicity and stratified by gender. The difference between men and women, and that across ethnicities and measurement types were compared by means of independent sample t-test and one-way ANOVA (SPSS v.24). Results: A total of 67 studies accounting for 22,638 patients and 118 ethnic cohorts were included in this pooled analysis. The most reported ethnicities were Middle Eastern (n = 6629) and Asian (n = 5473). ICD values (mm) in decreasing order were: African 38.5 ± 3.2, Asian 36.4 ± 1.6, Southeast Asian 32.8 ± 2.0, Hispanic 32.3 ± 2.0, White 31.4 ± 2.5, and Middle Eastern 31.2 ± 1.5. A statistically significant difference (P < 0.05) existed between all ethnic cohorts, between genders among most cohorts, and between most values stratified by measurement type. Conclusions: Our standards of craniofacial anthropometry must evolve from the neoclassical canons using White values as references. The values provided in this review can aid surgeons in appreciating the gender- and ethnic-specific differences in the ICD of their patients.

12.
JPRAS Open ; 19: 87-97, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32158860

RESUMO

INTRODUCTION: The objective of this study was to evaluate the safety and efficacy of fat grafting to the facial region for the reconstruction and aesthetic enhancement of facial contour. METHODS: A systematic literature review of the National Library of Medicine (PubMed), MEDLINE and Cochrane databases was performed. Studies involving the outcomes of autologous fat grafting to correct or enhance contour defects of the face were included. Extracted data included patient demographics, harvest and injection sites, graft harvesting and injection technique, mean injected volume, retained volume percentage and complications. RESULTS: Forty-three articles met the inclusion criteria, resulting in 4577 patients with various facial contour defects treated with autologous fat grafting. Injection sites were categorized by anatomic facial regions as upper (32.5%), middle (53%) and lower face (14.5%). The mean volume of injected fat was 16.9 ml. The mean weighted volume retention of non-enriched grafts was 41.63% at the time of follow up (mean 13.9 months). A total of 104 (2.27%) complications were reported including asymmetry (74), skin irregularities (14), prolonged edema (4), graft hypertrophy (4), fat necrosis (3), infection (2), erythema (1), telangiectasia (1), and activation of acne (1). CONCLUSION: The present study represents the first systematic review of fat grafting in the facial region, a widely-performed procedure within plastic surgery practice. Importantly, it presents pooled important data such as retained grafting volume and complication rates in this anatomical region, providing clinicians with more accurate information with which to guide their decision-making and patient education.

13.
J Cancer Prev ; 23(2): 93-98, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30003070

RESUMO

BACKGROUND: There is a paucity of data comparing the oncologic properties of breast cancer among patients previously having undergone breast augmentation in either the subglandular or subpectoral planes. The objective of the present systematic review was to evaluate whether implant location influenced the characteristics of breast tumors in previously augmented women. METHODS: A systematic literature search was performed to identify relevant articles reporting tumor characteristics in augmented patients. The search included published articles in three electronic databases; Ovid MEDLINE, EMBASE, and PubMed. Comparative studies (subglandular vs. subpectoral) were included. RESULTS: Analysis of data pooled from the included studies showed that subglandular implants had a higher frequency of tumors between 2 to 5 cm (26.5% vs. 9.9%, P = 0.0130). Subglandular implants also had a higher frequency of stage 2 tumors (42.9% vs. 23.7%, P = 0.0308). There was no significant difference in lymphovascular invasion between the 2 groups. These results of this systematic review suggest that the prognosis of patients undergoing augmentation is unaffected by implant location (subpectoral vs. subglandular). CONCLUSIONS: With the absence of large randomized controlled trials, our study provides surgeons with an evidence-based reference to improve informed consent with regards to implant placement.

14.
J Hypertens ; 35(7): 1390-1401, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28234672

RESUMO

AIMS: Peroxisome proliferator-activated receptor γ (PPARγ) agonists reduce blood pressure and vascular injury in hypertensive rodents. Pparγ inactivation in vascular smooth muscle cells (VSMC) enhances vascular injury. Transgenic mice overexpressing endothelin (ET)-1 selectively in the endothelium (eET-1) exhibit endothelial dysfunction, increased oxidative stress and inflammation. We hypothesized that inactivation of the Pparγ gene in VSMC (smPparγ-/-) would exaggerate ET-1-induced vascular injury. METHODS AND RESULTS: eET-1, smPparγ-/- and eET-1/smPparγ-/- mice were treated with tamoxifen for 5 days and studied 4 weeks later. SBP was higher in eET-1 and unaffected by smPparγ inactivation. Mesenteric artery vasodilatory responses to acetylcholine were impaired only in smPparγ-/-. N(omega)-Nitro-L-arginine methyl ester abrogated relaxation responses, and the Ednra/Ednrb mRNA ratio was decreased in eET-1/smPparγ-/-, which could indicate that nitric oxide production was enhanced by ET-1 stimulation of endothelin type B receptors. Mesenteric artery media/lumen was greater only in eET-1/smPparγ-/-. Mesenteric artery reactive oxygen species increased in smPparγ and were further enhanced in eET-1/smPparγ-/-. Perivascular fat monocyte/macrophage infiltration was higher in eET-1 and smPparγ and increased further in eET-1/smPparγ-/-. Spleen CD11b+ cells were increased in smPparγ-/- and further enhanced in eET-1/smPparγ-/-, whereas Ly-6C(hi) monocytes increased in eET-1 and smPparγ-/- but not in eET-1/smPparγ-/-. Spleen T regulatory lymphocytes increased in smPparγ and decreased in eET-1, and decreased further in eET-1/smPparγ-/-. CONCLUSION: VSMC Pparγ inactivation exaggerates ET-1-induced vascular injury, supporting a protective role for PPARγ in hypertension through modulation of pro-oxidant and proinflammatory pathways. Paradoxically, ET-1 overexpression preserved endothelial function in smPparγ-/- mice, presumably by enhancing nitric oxide through stimulation of endothelin type B receptors.


Assuntos
Endotelina-1/metabolismo , Inflamação/metabolismo , Músculo Liso Vascular/metabolismo , Estresse Oxidativo/fisiologia , PPAR gama/metabolismo , Animais , Endotelina-1/genética , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Inflamação/genética , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Camundongos , Camundongos Transgênicos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/genética , Espécies Reativas de Oxigênio/metabolismo
15.
Am J Hypertens ; 29(11): 1245-1251, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27465439

RESUMO

BACKGROUND: Increased endothelin (ET)-1 expression causes endothelial dysfunction and oxidative stress. Plasma ET-1 is increased in patients with diabetes mellitus. Since endothelial dysfunction often precedes vascular complications in diabetes, we hypothesized that overexpression of ET-1 in the endothelium would exaggerate diabetes-induced endothelial dysfunction. METHODS: Diabetes was induced by streptozotocin treatment (55mg/kg/day, i.p.) for 5 days in 6-week-old male wild type (WT) mice and in mice overexpressing human ET-1 restricted to the endothelium (eET-1). Mice were studied 14 weeks later. Small mesenteric artery (MA) endothelial function and vascular remodeling by pressurized myography, reactive oxygen species (ROS) production by dihydroethidium staining and mRNA expression by reverse transcription/quantitative PCR were determined. RESULTS: Endothelium-dependent vasodilatory responses to acetylcholine of MA were reduced 24% by diabetes in WT ( P < 0.05), and further decreased by 12% in eET-1 ( P < 0.05). Diabetes decreased MA media/lumen in WT and eET-1 ( P < 0.05), whereas ET-1 overexpression increased MA media/lumen similarly in diabetic and nondiabetic WT mice ( P < 0.05). Vascular ROS production was increased 2-fold by diabetes in WT ( P < 0.05) and further augmented 1.7-fold in eET-1 ( P < 0.05). Diabetes reduced endothelial nitric oxide synthase (eNOS, Nos3 ) expression in eET-1 by 31% ( P < 0.05) but not in WT. Induction of diabetes caused a 52% ( P < 0.05) increase in superoxide dismutase 1 ( Sod1 ) and a 32% ( P < 0.05) increase in Sod2 expression in WT but not in eET-1. CONCLUSIONS: Increased expression of ET-1 exaggerates diabetes-induced endothelial dysfunction. This may be caused by decrease in eNOS expression, increase in vascular oxidative stress, and decrease in antioxidant capacity.


Assuntos
Diabetes Mellitus , Endotelina-1 , Estresse Oxidativo , Animais , Diabetes Mellitus/metabolismo , Endotelina-1/metabolismo , Endotélio Vascular/fisiopatologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico , Óxido Nítrico Sintase Tipo III/metabolismo , Espécies Reativas de Oxigênio
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