RESUMO
BACKGROUND: There is accumulating evidence that extracellular adenosine triphosphate (eATP) promotes many of the underlying mechanisms that exacerbate acute lung injury. However, much of these data are from inbred rodent models, indicating the need for further investigation in higher vertebrates to better establish clinical relevance. To this end we evaluated a human recombinant apyrase therapy in a canine warm pulmonary ischemia-reperfusion injury (IRI) model and measured eATP levels in human lung recipients with or without primary lung graft dysfunction (PGD). METHODS: Warm ischemia was induced for 90 minutes in the left lung of 14 mongrel dogs. Seven minutes after reperfusion, the apyrase APT102 (1 mg/kg, n = 7) or saline vehicle (n = 7) was injected into the pulmonary artery. Arterial blood gases were obtained every 30 minutes up to 180 minutes after reperfusion. Bronchioalveolar lavage fluid (BALF) was analyzed for eATP concentration, cellularity, and inflammatory mediator accumulation. Thirty bilateral human lung transplant recipients were graded for immediate early PGD and assessed for BALF eATP levels. RESULTS: APT102-treated dogs had progressively better lung function and less pulmonary edema during the 3-hour reperfusion period compared with vehicle-treated controls. Protection from IRI was observed, with lower BALF eATP levels, fewer airway leukocytes, and blunted inflammatory mediator expression. Human lung recipients with moderate to severe PGD had significantly higher eATP levels compared with recipients without this injury. CONCLUSIONS: Extracellular ATP accumulates in acutely injured canine and human lungs. Strategies that target eATP reduction may help protect lung recipients from IRI.
Assuntos
Apirase/uso terapêutico , Pneumopatias/prevenção & controle , Transplante de Pulmão , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Cães , Humanos , Disfunção Primária do Enxerto , Proteínas Recombinantes/uso terapêuticoRESUMO
OBJECTIVES: A limited number of patients undergoing coronary artery bypass grafting (CABG) currently receive bilateral internal thoracic arteries (BITA) as a consequence of lack of evidence on survival benefit and concerns about sternal wound complications. This study was undertaken to determine the impact of BITA grafting on short- and long-term outcomes in obese patients. METHODS: Propensity score matching for short- and long-term outcomes was conducted for 1522 obese (body mass index ≥ 30 kg/m(2)) patients undergoing CABG using BITA (n = 229, 15.0%) or a single internal thoracic artery (SITA, n = 1293, 85.0%). RESULTS: Propensity score matching created 229 matching sets. In the matched sample, operative mortality (within 30 days) occurred in 3 (1.3%) and 4 (1.7%) patients in the BITA and SITA groups, respectively (P = 1). Deep sternal wound infection occurred in 6 (2.6%) and 2 (0.9%) patients (P = .2) in the BITA and SITA group, respectively. After a median follow-up of 4.5 ± 3.3 years, the use of BITA was associated with an improved late survival (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.13-0.97; P = .03) and a reduced need for repeat revascularization (HR, 0.45; 95% CI, 0.23-0.85; P = .01). CONCLUSIONS: BITA grafting can be safely offered to obese patients with significant long-term advantages without substantial additional risk of operative complications including deep sternal wound infection.
Assuntos
Doença da Artéria Coronariana/cirurgia , Anastomose de Artéria Torácica Interna-Coronária/métodos , Artéria Torácica Interna/cirurgia , Obesidade/complicações , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Bases de Dados Factuais , Feminino , Humanos , Anastomose de Artéria Torácica Interna-Coronária/efeitos adversos , Anastomose de Artéria Torácica Interna-Coronária/mortalidade , Londres , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/mortalidade , Segurança do Paciente , Seleção de Pacientes , Pontuação de Propensão , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Atrial fibrillation (AF) is the most prevalent arrhythmia encountered in clinical practice with greater than 2.2 million people in the United States being affected. Oral anticoagulant therapy has been used to reduce risk of stroke in patients with nonvalvular AF who are at a high risk of thromboembolism. Alternative treatment strategies to prevent thromboembolism have been tested in patients with AF. This article examines the history of left atrial appendage occlusion and the efficacy of the various surgical techniques and provides a brief overview of the minimally invasive surgical strategy adopted to manage the left atrial appendage.
RESUMO
OBJECTIVES: This study aimed at identifying the ideal right-to-left shunt-fraction to improve cardiac output (CO) and systemic perfusion in pulmonary arterial hypertension (PHT). BACKGROUND: Atrial septostomy (AS) has been a high-risk therapeutic option for symptomatic drug-refractory patients with PHT. Results have been unpredictable due to limited knowledge of the optimal shunt-quantity. METHODS: In nine dogs, an 8-mm shunt-prosthesis was inserted between the superior vena cava (SVC) and the left atrium. With pulmonary artery (PA) banding, mean (± SEM) systolic right ventricular pressure increased from 37 ± 1 mm Hg at baseline to 44 ± 1 mm Hg (moderate PHT, P = 0.005) and 50 ± 2 mm Hg (severe PHT, P < 0.001). Shunt-flow was adjusted by total (forcing all flow through the shunt) or partial occlusion of the SVC and partial or total clamping of the shunt. Caval-, shunt-, and aortic-flow were measured by ultrasonic flow-probes. Blood gases were drawn from the aortic root and PA. RESULTS: At severe PHT, a shunt-flow of 11 ± 1% of CO (253 ± 90 mL/min) increased CO significantly by 25% (1.8 ± 0.1 to 2.4 ± 0.2 L/min, P = 0.005) causing an increase of systemic oxygen delivery index (DO2 I) by 23% (309 ± 23 to 399 ± 32 mL/min/m(2), P = 0.035). Arterial O2 -saturation did not change significantly until a shunt-flow of 18 ± 2% was exceeded, causing a drop from 96 ± 1% to 84 ± 4% (P = 0.013). At moderate PHT, CO or DO2 I did not improve significantly at any shunt-flow. CONCLUSIONS: In severe PHT, a shunt-flow of 11% of CO represented the ideal shunt-fraction. Augmentation of CO compensated for declined O2 -saturation due to right-to-left shunting and improved DO2 I. In moderate PHT, AS is less promising.