Effects of Obesity on Pulmonary Inflammation and Remodeling in Experimental Moderate Acute Lung Injury.

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.

Biologic Impact of Mechanical Power at High and Low Tidal Volumes in Experimental Mild Acute Respiratory Distress Syndrome.

BACKGROUND: The authors hypothesized that low tidal volume (VT) would minimize ventilator-induced lung injury regardless of the degree of mechanical power. The authors investigated the impact of power, obtained by different combinations of VT and respiratory rate (RR), on ventilator-induced lung injury in experimental mild acute respiratory distress syndrome (ARDS). METHODS: Forty Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 32 rats were randomly assigned to be mechanically ventilated (2 h) with a combination of different VT (6 ml/kg and 11 ml/kg) and RR that resulted in low and high power. Power was calculated as energy (ΔP,L/E,L) × RR (ΔP,L = transpulmonary driving pressure; E,L = lung elastance), and was threefold higher in high than in low power groups. Eight rats were not mechanically ventilated and used for molecular biology analysis. RESULTS: Diffuse alveolar damage score, which represents the severity of edema, atelectasis, and overdistension, was increased in high VT compared to low VT, in both low (low VT: 11 [9 to 14], high VT: 18 [15 to 20]) and high (low VT: 19 [16 to 25], high VT: 29 [27 to 30]) power groups. At high VT, interleukin-6 and amphiregulin expressions were higher in high-power than in low-power groups. At high power, amphiregulin and club cell protein 16 expressions were higher in high VT than in low VT. Mechanical energy and power correlated well with diffuse alveolar damage score and interleukin-6, amphiregulin, and club cell protein 16 expression. CONCLUSIONS: In experimental mild ARDS, even at low VT, high mechanical power promoted ventilator-induced lung injury. To minimize ventilator-induced lung injury, low VT should be combined with low power.

Biological Response to Time-Controlled Adaptive Ventilation Depends on Acute Respiratory Distress Syndrome Etiology.

OBJECTIVES: To compare a time-controlled adaptive ventilation strategy, set in airway pressure release ventilation mode, versus a protective mechanical ventilation strategy in pulmonary and extrapulmonary acute respiratory distress syndrome with similar mechanical impairment. DESIGN: Animal study. SETTING: Laboratory investigation. SUBJECTS: Forty-two Wistar rats. INTERVENTIONS: Pulmonary acute respiratory distress syndrome and extrapulmonary acute respiratory distress syndrome were induced by instillation of Escherichia coli lipopolysaccharide intratracheally or intraperitoneally, respectively. After 24 hours, animals were randomly assigned to receive 1 hour of volume-controlled ventilation (n = 7/etiology) or time-controlled adaptive ventilation (n = 7/etiology) (tidal volume = 8 mL/kg). Time-controlled adaptive ventilation consisted of the application of continuous positive airway pressure 2 cm H2O higher than baseline respiratory system peak pressure for a time (Thigh) of 0.75-0.85 seconds. The release pressure (Plow = 0 cm H2O) was applied for a time (Tlow) of 0.11-0.18 seconds. Tlow was set to target an end-expiratory flow to peak expiratory flow ratio of 75%. Nonventilated animals (n = 7/etiology) were used for Diffuse Alveolar Damage and molecular biology markers analyses. MEASUREMENT AND MAIN RESULTS: Time-controlled adaptive ventilation increased mean respiratory system pressure regardless of acute respiratory distress syndrome etiology. The Diffuse Alveolar Damage score was lower in time-controlled adaptive ventilation compared with volume-controlled ventilation in pulmonary acute respiratory distress syndrome and lower in time-controlled adaptive ventilation than nonventilated in extrapulmonary acute respiratory distress syndrome. In pulmonary acute respiratory distress syndrome, volume-controlled ventilation, but not time-controlled adaptive ventilation, increased the expression of amphiregulin, vascular cell adhesion molecule-1, and metalloproteinase-9. Collagen density was higher, whereas expression of decorin was lower in time-controlled adaptive ventilation than nonventilated, independent of acute respiratory distress syndrome etiology. In pulmonary acute respiratory distress syndrome, but not in extrapulmonary acute respiratory distress syndrome, time-controlled adaptive ventilation increased syndecan expression. CONCLUSION: In pulmonary acute respiratory distress syndrome, time-controlled adaptive ventilation led to more pronounced beneficial effects on expression of biomarkers related to overdistension and extracellular matrix homeostasis.