Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice

<p>Abstract</p> <p>Background</p> <p>Deep inspirations (DI) have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation.</p> <p>Methods</p> <p>Balb/c mice were sensitized to ovalbumin (OVA) and exposed to nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which were given twice during the minute before assessment of lung mechanics.</p> <p>Results</p> <p>DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8 ± 0.3 to 2.8 ± 0.1 cmH₂O·s·mL^-1in healthy mice and 5.1 ± 0.3 to 3.5 ± 0.3 cmH₂O·s·mL^-1in acute airway inflammation (both <it>P </it>< 0.001). In healthy mice, DI reduced the maximum decrease in lung compliance from 15.9 ± 1.5% to 5.6 ± 0.6% (<it>P </it>< 0.0001). This protective effect was even more pronounced in mice with chronic inflammation where DI attenuated maximum decrease in compliance from 44.1 ± 6.6% to 14.3 ± 1.3% (<it>P </it>< 0.001). DI largely prevented increased peripheral tissue damping (G) and tissue elastance (H) in both healthy (G and H both <it>P </it>< 0.0001) and chronic allergen-treated animals (G and H both <it>P </it>< 0.0001).</p> <p>Conclusion</p> <p>We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.</p

Effects of Bone Marrow-Derived Mononuclear Cells From Healthy or Acute Respiratory Distress Syndrome Donors on Recipient Lung-Injured Mice.

The advantage of using autologous bone marrow-derived mononuclear cells to treat acute respiratory distress syndrome patients is to prevent immunological rejection. However, bone marrow-derived mononuclear cells may be altered by different acute respiratory distress syndrome etiologies, resulting in questionable efficacy and thus limited clinical application. We aimed to investigate the effects of bone marrow-derived mononuclear cells obtained from healthy and acute respiratory distress syndrome donors on pulmonary and extrapulmonary acute respiratory distress syndrome. DESIGN:: Prospective, randomized, controlled experimental study. SETTING:: University research laboratory. SUBJECTS:: Two hundred and twenty-five C57BL/6 mice. INTERVENTIONS:: Acute respiratory distress syndrome was induced by Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). Control mice (Healthy) received saline solution intratracheally (Cp) or intraperitoneally (Cexp). After 24 hours, whole bone marrow cells were analyzed in vitro: 1) colony-forming unit-fibroblasts and 2) hematopoietic stem cells, neutrophils, T helper lymphocytes, B lymphocytes, and nonhematopoietic precursors. After cell characterization, all groups received saline or bone marrow-derived mononuclear cells (2 7 106), obtained from Cp, Cexp, ARDSp, and ARDSexp donor mice, IV, on day 1. MEASUREMENTS AND MAIN RESULTS:: On day 1, in ARDSp, different patterns of colony formation were found, with nonstromal cells (mainly neutrophils) predominating over fibroblastoid colonies. In ARDSexp, irregular colony-forming unit-fibroblasts morphology with dispersed proliferating colonies and a greater number of hematopoietic stem cells were observed. In ARDSp, colony-forming unit-fibroblasts count was higher but not measurable in ARDSexp. In ARDSp, monocytes and T lymphocytes were increased and hematopoietic precursor cells reduced, with no significant changes in ARDSexp. On day 7, bone marrow-derived mononuclear cells improved survival and attenuated changes in lung mechanics, alveolar collapse, inflammation, pulmonary fibrosis, and apoptosis in the lung and distal organs, regardless of donor type. CONCLUSIONS:: Bone marrow-derived mononuclear cells from ARDSp and ARDSexp donors showed different characteristics but were as effective as cells obtained from healthy donors in reducing inflammation and remodeling, suggesting the utility of autologous transplant of bone marrow-derived mononuclear cells in the clinical setting