RESUMO
Endothelial barrier dysfunction is an important contributor to the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Even though approaches that target the prevention and repair of endothelial barrier dysfunction are clearly needed, our understanding of the molecular regulation of pulmonary microvascular endothelial permeability remains incomplete. Cultured pulmonary microvascular endothelial cells represent an attractive paradigm for the study of barrier function. Here, we describe a method for the harvest, identification and culture of human lung microvascular endothelial cells (HLMVEC). HLMVEC thus obtained, grow as a monolayer, exhibit contact inhibition and have the typical cobblestone appearance. They express endothelial proteins, such as von Willebrand factor and endothelial nitric oxide synthase and take up an acetylated LDL. Furthermore, HLMVEC respond predictably and with superior sensitivity to the barrier disruptive effects of Gram positive and Gram negative bacterial products, thrombin, vascular endothelial growth factor and microtubule disrupting agents. These HLMVEC present an in-house-derived alternative to commercially available human cells for the study of mechanisms contributing to ALI and ARDS.
Assuntos
Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Pulmão/citologia , Lesão Pulmonar Aguda/fisiopatologia , Técnicas de Cultura de Células/métodos , Células Cultivadas , Endotélio Vascular/metabolismo , Humanos , Microvasos , Óxido Nítrico Sintase Tipo III/metabolismo , Permeabilidade , Síndrome do Desconforto Respiratório/fisiopatologia , Fator de von Willebrand/metabolismoRESUMO
OBJECTIVES: Mediastinal radiation for thoracic malignancies uses multiple treatment fields and doses. We investigated whether more extensive radiation exposure is associated with more hospital complications and worse survival after cardiac surgery. METHODS: From January 2000 to January 2005, 230 patients underwent cardiac surgery after 3 levels of mediastinal radiation: extensive (Hodgkin disease, thymoma, and testicular cancer; n = 70), variable (eg, non-Hodgkin lymphoma and lung cancer; n = 35); and tangential (breast cancer; n = 125). Hospital complications were recorded prospectively, and time-related survival was assessed by patient follow-up (mean follow-up, 2.2 +/- 1.4 years). RESULTS: Patients receiving extensive exposure were youngest (51 vs 64 vs 72 years), with the longest radiation-to-operation interval (25 vs 13 vs 14 years), and had the most diastolic dysfunction, left main stenosis of greater than 70% (21% vs 9% vs 8%), and aortic regurgitation (79% vs 54% vs 50%). Patients receiving extensive and variable exposure had the poorest pulmonary function (percent predicted forced expiratory volume in 1 second, 57% vs 54% vs 67%; percent predicted forced vital capacity, 56% vs 63% vs 66%). All groups received a similar mix of cardiac procedures. Hospital deaths (13% vs 8.6% vs 2.4%) and respiratory complications (24% vs 20% vs 9.6%) were higher after more extensive radiation, and survival was poorer (4-year survival, 64% vs 57% vs 80%) than for patients receiving tangential radiation exposure, and it deviated more from expected matched-population life tables. CONCLUSIONS: Among patients undergoing cardiac surgery after thoracic radiation, radiation exposure is heterogeneous, and therefore these patients cannot be managed and assessed as a single uniform cohort. Extensively irradiated patients are more likely to develop radiation heart disease, which increases perioperative morbidity and decreases short- and long-term survival.
Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Cardiopatias/mortalidade , Neoplasias do Mediastino/diagnóstico por imagem , Lesões por Radiação/complicações , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/métodos , Estudos de Coortes , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Cardiopatias/diagnóstico , Cardiopatias/cirurgia , Mortalidade Hospitalar , Humanos , Masculino , Neoplasias do Mediastino/mortalidade , Neoplasias do Mediastino/patologia , Mediastino/efeitos da radiação , Pessoa de Meia-Idade , Doses de Radiação , Radiografia , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Análise de SobrevidaRESUMO
Regional referral networks ("hub and spoke") have been created to facilitate the transfer of patients on mechanical circulatory support. Although individual centers report good success, overall outcomes have remained poor. We investigated whether preoperative variables influenced survival and could be used to help select patients best served by referral. A retrospective chart review was conducted on all patients transferred to our institution supported on cardiac assist devices. Between January 1995 and September 2003, 39 patients were received in transfer for continued care after the implantation of a cardiac assist device. Eighty-five percent of patients had the ABIOMED BVS 5000 implanted. The most common indication was postcardiotomy shock. Sixty-four percent of patients were not candidates for heart transplantation due to medical or social contraindications. The 30-day mortality of this group was 62%. Survivors had less comorbidity and were less likely to have complex surgeries, neurologic impairment, and multisystem organ failure when presenting to our center. Devices were weaned in 30% of cases. Only six patients (15%) were successfully transplanted, and five of these patients have done well at follow-up. Based on our experience, we believe that cardiogenic shock patients benefit from a regional referral system if they have not had complex cardiac surgical procedures or developed multisystem organ failure. Furthermore, there is a survival advantage when using long-term devices because this allows possible recovery or transplantation.
Assuntos
Fundações , Serviços de Saúde , Coração Auxiliar , Encaminhamento e Consulta , Adulto , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Causas de Morte , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Choque Cardiogênico/etiologia , Choque Cardiogênico/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Patients bridged to heart transplantation with a ventricular assist device (VAD) developed coronary vasculopathy at the same rate as non-bridged patients despite having higher levels of pre-formed antibodies. We hypothesized that allosensitized VAD patients have higher levels of immunosuppression and thus different morbidity and causes of mortality. METHODS: Patients who received a transplant between January 1996 and May 2002 were separated into 2 groups based on the need for VAD support as a bridge to transplantation. Transplant and Inpatient Pharmacy Databases and charts were queried for date of transplantation, degree of allosensitization, use of desensitization therapy, immunosuppressive strategies, number of treated rejection episodes, and specific causes of death. RESULTS: This study investigated 238 patients (125 VAD patients, 113 non-VAD patients). VAD patients were more likely to be allosensitized than non-VAD patients (20% vs 5%, p < 0.01). OKT3 was given to 22% of VAD patients as anti-rejection prophylaxis and 14% received pre-transplant plasmapheresis. Non-VAD patients rarely were desensitized (2.6% of non-VAD patients). After transplantation, 68 VAD patients (54%) and 44 non-VAD patients (39%) had episodes of severe rejection requiring therapy. Episodes of rejection in VAD patients were commonly treated with steroids (90%), plasmapheresis (10%), and OKT3 (7%), and episodes of rejection in non-VAD patients were treated with steroids (76%) and OKT3 (8%). The 5-year survival for both groups was similar (90% and 86% respectively, p = 0.31). VAD patients commonly died of sepsis (75%), and non-VAD patients died of rejection (39%) and ischemic transplant cardiomyopathy (30%). CONCLUSION: When short-term outcomes between bridged and non-bridged heart transplant recipients were compared, overall survival was similar but causes of death differed. Findings in this study might aid in the post-operative management of patients bridged to transplantation with a VAD.
Assuntos
Soro Antilinfocitário/uso terapêutico , Transplante de Coração/imunologia , Coração Auxiliar , Imunossupressores/uso terapêutico , Muromonab-CD3/uso terapêutico , Idoso , Soro Antilinfocitário/administração & dosagem , Causas de Morte , Doença das Coronárias/imunologia , Doença das Coronárias/prevenção & controle , Doença das Coronárias/cirurgia , Feminino , Rejeição de Enxerto/tratamento farmacológico , Transplante de Coração/mortalidade , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Fragmentos de Peptídeos , Plasmaferese , Estudos Retrospectivos , Sepse/epidemiologia , Linfócitos T/imunologiaRESUMO
BACKGROUND: Coronary transplant vasculopathy (CAV) has been associated with both immunologic and nonimmunologic factors. The impact of preoperative ventricular assist device (VAD) support on the development of CAV has not been studied. To examine this, we obtained posttransplant coronary angiograms from a group of patients bridged with VAD and compared them to post transplant coronary angiograms of a non-VAD cohort. METHODS: Adult patients undergoing orthotopic heart transplant between 1996-2000 were retrospectively studied and divided into VAD and non-VAD patients. Coronary angiograms were retrospectively reviewed and severity of coronary vasculopathy was categorized as trivial, mild, moderate, or severe. Other variables studied included recipient and donor demographics, cytotoxic panel reactive antibodies (PRA) against T-cell targets and flow cytometric crossmatching against donor T lymphocytes. RESULTS: There was no significant difference between groups regarding demographics. However, VAD patients had a sixfold greater chance of having a T-cell PRA >10% at the time of transplant (p < 0.05), and a fourfold greater chance of having a positive cross match when compared to non-VAD patients (p < 0.05). There was no significant difference in the degree of CAV between groups. Normal coronary anatomy was present in 76% of VAD patients and 64% of non-VAD patients (p = 0.37). These results were similar at 2- and 3-year follow-up (76 vs. 74% and 80 vs. 62%, respectively). CONCLUSION: Preoperative VAD use is associated with increased sensitization; however, these patients develop CAV at the same rate as those not bridged with a VAD.