Angeli P, Prado CM, Xisto DG, Silva PL, Pá ssaro CP, Nakazato HD, Leick-Maldonado EA, Martins MA, Rocco PR, Tibério IF. Effects of chronic L-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation.

In vivo (lung resistive and viscoelastic pressures and static elastance) and in vitro (tissue resistance, elastance, and hysteresivity) respiratory mechanics were analyzed 1 and 30 days after saline (control) or paraquat (P [10 and 25 mg/kg intraperitoneally]) injection in rats. Additionally, P10 and P25 were treated with methylprednisolone (2 mg/kg intravenously) at 1 or 6 hours after acute lung injury (ALI) induction. Collagen and elastic fibers were quantified. Lung resistive and viscoelastic pressures and static elastance were higher in P10 and P25 than in the control. Tissue elastance and resistance augmented from control to P10 (1 and 30 days) and P25. Hysteresivity increased in only P25. Methylprednisolone at 1 or 6 hours attenuated in vivo and in vitro mechanical changes in P25, whereas P10 parameters were similar to the control. Collagen increment was dose and time dependent. Elastic fibers increased in P25 and at 30 days in P10. Corticosteroid prevented collagen increment and avoided elastogenesis. In conclusion, methylprednisolone led to a complete maintenance of in vivo and in vitro respiratory mechanics in mild lesion, whereas it minimized the changes in tissue impedance and extracellular matrix in severe ALI. The beneficial effects of the early use of steroids in ALI remained unaltered at Day 30.

In the present nonrecruited ALI model, protective mechanical ventilation with lower and higher PEEP levels than required for better oxygenation increased Est, L and DeltaP2, L, the amount of atelectasis, and PCIII mRNA expression. PEEP selection titrated for a minimum elastance and maximum oxygenation may prevent lung injury while deviation from these settings may be harmful.

Undernutrition thwarts lung structure and function, but there are disagreements about the behavior of lung mechanics in malnourished animals. To clarify this issue, lung and chest wall mechanical properties were subdivided into their resistive, elastic, and viscoelastic properties in nutritionally deprived (ND) rats and correlated with the data gathered from histology (light and electron microscopy and elastic fiber content), and bronchoalveolar lavage fluid analysis (lipid and protein content). Twenty-four Wistar rats were assigned into two groups. In the control (Ctrl) group the animals received food ad libitum. In the ND group, rats received one-third of their usual daily food consumption until they lost 40% of their initial body weight. Lung static elastance, viscoelastic and resistive pressures (normalized by functional residual capacity), and chest wall pressures were higher in the ND group than in the Ctrl group. The ND group exhibited patchy atelectasis, areas of emphysema, interstitial edema, and reduced elastic fiber content. The amount of lipid and protein in bronchoalveolar lavage fluid was significantly reduced in the ND group. Electron microscopy showed 1) type II pneumocytes with a reduction in lamellar body content, multilamellated structures, membrane vesicles, granular debris, and structurally aberrant mitochondria; and 2) diaphragm and intercostals with atrophy, disarrangement of the myofibrils, and deposition of collagen type I fibers. In conclusion, undernutrition led to lung and chest wall mechanical changes that were the result from a balance among the following modifications: 1) distorted structure of diaphragm and intercostals, 2) surfactant content reduction, and 3) decrease in elastic fiber content.

The time course of lung mechanics, histology, and inflammatory and fibrogenic mediators are analysed after intratracheal instillation (IT) of bone marrow-derived cells (BMDC) in a model of silicosis. C57BL/6 mice were randomly divided into SIL (silica, 20mg IT) and control (CTRL) groups (saline IT). At day 15, mice received saline or BMDC (2 x 10(6)cells) IT. The biodistribution of technetium-99m BMDC was higher in lungs compared with other organs. At days 30 and 60, lung mechanics, the area of granulomatous nodules, and mRNA expression of IL-1beta and TGF-beta were higher in SIL than CTRL animals. BMDC minimized changes in lung mechanics, the area of granulomatous nodules, and total cell infiltration at day 30, but these effects were no longer observed at day 60. Conversely, BMDC avoided the expression of IL-1beta at days 30 and 60 and TGF-beta only at day 30. In conclusion, BMDC therapy improved lung mechanics and histology, but this beneficial effect was not maintained in the course of injury.

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