RESUMO
Obese patients are at higher risk of developing acute respiratory distress syndrome (ARDS); however, their survival rates are also higher compared to those of similarly ill non-obese patients. We hypothesized that obesity would not only prevent lung inflammation, but also reduce remodeling in moderate endotoxin-induced acute lung injury (ALI). Obesity was induced by early postnatal overfeeding in Wistar rats in which the litter size was reduced to 3 pups/litter (Obese, n = 18); Control animals (n = 18) were obtained from unculled litters. On postnatal day 150, Control, and Obese animals randomly received E. coli lipopolysaccharide (ALI) or saline (SAL) intratracheally. After 24 h, echocardiography, lung function and morphometry, and biological markers in lung tissue were evaluated. Additionally, mediator expression in neutrophils and macrophages obtained from blood and bronchoalveolar lavage fluid (BALF) was analyzed. Compared to Control-SAL animals, Control-ALI rats showed no changes in echocardiographic parameters, increased lung elastance and resistance, higher monocyte phagocytic capacity, collagen fiber content, myeloperoxidase (MPO) activity, and levels of interleukin (IL-6), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, and type III (PCIII), and I (PCI) procollagen in lung tissue, as well as increased expressions of TNF-α and monocyte chemoattractant protein (MCP)-1 in blood and BALF neutrophils. Monocyte (blood) and macrophage (adipose tissue) phagocytic capacities were lower in Obese-ALI compared to Control-ALI animals, and Obese animals exhibited reduced neutrophil migration compared to Control. Obese-ALI animals, compared to Obese-SAL, exhibited increased interventricular septum thickness (p = 0.003) and posterior wall thickness (p = 0.003) and decreased pulmonary acceleration time to pulmonary ejection time ratio (p = 0.005); no changes in lung mechanics, IL-6, TNF-α, TGF-ß, PCIII, and PCI in lung tissue; increased IL-10 levels in lung homogenate (p = 0.007); reduced MCP-1 expression in blood neutrophils (p = 0.009); decreased TNF-α expression in blood (p = 0.02) and BALF (p = 0.008) neutrophils; and increased IL-10 expression in monocytes (p = 0.004). In conclusion, after endotoxin challenge, obese rats showed less deterioration of lung function, secondary to anti-inflammatory and anti-fibrotic effects, as well as changes in neutrophil and monocyte/macrophage phenotype in blood and BALF compared to Control rats.
Assuntos
Lesão Pulmonar Aguda/fisiopatologia , Obesidade/fisiopatologia , Pneumonia/fisiopatologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/etiologia , Animais , Líquido da Lavagem Broncoalveolar , Quimiotaxia de Leucócito , Colágeno/metabolismo , Citocinas/biossíntese , Citocinas/genética , Feminino , Fibrose , Regulação da Expressão Gênica , Septos Cardíacos/patologia , Lipopolissacarídeos/toxicidade , Pulmão/patologia , Pulmão/fisiopatologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Neutrófilos/imunologia , Neutrófilos/metabolismo , Obesidade/complicações , Hipernutrição/complicações , Peroxidase/análise , Fagocitose , Pneumonia/induzido quimicamente , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/fisiopatologia , Ratos , Ratos WistarRESUMO
Intraoperative positive end-expiratory pressure (PEEP) has been proposed to restore lung volumes and improve respiratory function in obesity. However, the biological impact of different PEEP levels on the lungs in obesity remains unknown. We aimed to compare the effects of PEEP = 2 cmH2O versus PEEP = 6 cmH2O during ventilation with low tidal volumes on lung function, histology, and biological markers in obese and non-obese rats undergoing open abdominal surgery. Forty-two Wistar rats (21 obese, 21 non-obese) were anesthetized and tracheotomized, and laparotomy was performed with standardized bowel manipulation. Rats were randomly ventilated with protective tidal volume (7 ml/kg) at PEEP = 2 cmH2O or PEEP = 6 cmH2O for 4 h, after which they were euthanized. Lung mechanics and histology, alveolar epithelial cell integrity, and biological markers associated with pulmonary inflammation, alveolar stretch, extracellular matrix, and epithelial and endothelial cell damage were analyzed. In obese rats, PEEP = 6 cmH2O compared with PEEP = 2 cmH2O was associated with less alveolar collapse (p = 0.02). E-cadherin expression was not different between the two PEEP groups. Gene expressions of interleukin (IL)-6 (p = 0.01) and type III procollagen (p = 0.004), as well as protein levels of tumor necrosis factor-alpha (p = 0.016), were lower at PEEP = 6 cmH2O than at PEEP = 2 cmH2O. In non-obese animals, PEEP = 6 cmH2O compared with PEEP = 2 cmH2O led to increased hyperinflation, reduced e-cadherin (p = 0.04), and increased gene expression of IL-6 (p = 0.004) and protein levels of tumor necrosis factor-alpha (p-0.029), but no changes in fibrogenesis. In conclusion, PEEP = 6 cmH2O reduced lung damage and inflammation in an experimental model of mechanical ventilation for open abdominal surgery, but only in obese animals.