During PSV, PEEP of 5 cmH2O, but not a PEEP of 2 cmH2O, reduced lung damage and inflammatory markers while maintaining epithelial cell integrity.

BackgroundEmphysema is a progressive disease characterized by irreversible airspace enlargement followed by a decline in lung function. It also causes extrapulmonary effects, such as loss of body mass and cor pulmonale, which are associated with shorter survival and worse clinical outcomes. Ghrelin, a growth-hormone secretagogue, stimulates muscle anabolism, has anti-inflammatory effects, promotes vasodilation, and improves cardiac performance. Therefore, we hypothesized that ghrelin might reduce lung inflammation and remodelling as well as improve lung mechanics and cardiac function in experimental emphysema.MethodsForty female C57BL/6 mice were randomly assigned into two main groups: control (C) and emphysema (ELA). In the ELA group (n=20), animals received four intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals. C animals (n=20) received saline alone (50 μL) using the same protocol. Two weeks after the last instillation of saline or PPE, C and ELA animals received ghrelin or saline (n=10/group) intraperitoneally (i.p.) daily, during 3 weeks. Dual-energy X-ray absorptiometry (DEXA), echocardiography, lung mechanics, histology, and molecular biology were analysed.ResultsIn elastase-induced emphysema, ghrelin treatment decreased alveolar hyperinflation and mean linear intercept, neutrophil infiltration, and collagen fibre content in the alveolar septa and pulmonary vessel wall; increased elastic fibre content; reduced M1-macrophage populations and increased M2 polarization; decreased levels of keratinocyte-derived chemokine (KC, a mouse analogue of interleukin-8), tumour necrosis factor-α, and transforming growth factor-β, but increased interleukin-10 in lung tissue; augmented static lung elastance; reduced arterial pulmonary hypertension and right ventricular hypertrophy on echocardiography; and increased lean mass.ConclusionIn the elastase-induced emphysema model used herein, ghrelin not only reduced lung damage but also improved cardiac function and increased lean mass. These findings should prompt further studies to evaluate ghrelin as a potential therapy for emphysema.Electronic supplementary materialThe online version of this article (10.1186/s12931-017-0668-9) contains supplementary material, which is available to authorized users.

BackgroundIn patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema.MethodsEmphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks. Control animals received saline under the same protocol. Eight weeks after first instillation, control and emphysema rats were randomly assigned to PCV (n = 6/each) or PSV (n = 6/each) under protective tidal volume (6 ml/kg) for 4 h. Non-ventilated control and emphysema animals (n = 6/group) were used to characterize the model and for molecular biology analysis. Cardiorespiratory function, lung histology, diaphragm ultrastructure alterations, extracellular matrix organization, diaphragmatic proteolysis, and biological markers associated with pulmonary inflammation, alveolar stretch, and epithelial and endothelial cell damage were assessed.ResultsEmphysema animals exhibited cardiorespiratory changes that resemble human emphysema, such as increased areas of lung hyperinflation, pulmonary amphiregulin expression, and diaphragmatic injury. In emphysema animals, PSV compared to PCV yielded: no changes in gas exchange; decreased mean transpulmonary pressure (Pmean,L), ratio between inspiratory and total time (Ti/Ttot), lung hyperinflation, and amphiregulin expression in lung; increased ratio of pulmonary artery acceleration time to pulmonary artery ejection time, suggesting reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm. Amphiregulin correlated with Pmean,L (r = 0.99, p < 0.0001) and hyperinflation (r = 0.70, p = 0.043), whereas Ti/Ttot correlated with hyperinflation (r = 0.81, p = 0.002) and Pmean,L (r = 0.60, p = 0.04).ConclusionsIn the model of elastase-induced emphysema used herein, PSV reduced lung damage and improved cardiac function when compared to PCV, but worsened diaphragmatic injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-016-0107-0) contains supplementary material, which is available to authorized users.

Background/Aims: Exogenous surfactant has been proposed as adjunctive therapy for acute respiratory distress syndrome (ARDS), but it is inactivated by different factors present in the alveolar space. We hypothesized that co-administration of LASSBio596, a molecule with significant anti-inflammatory properties, and exogenous surfactant could reduce lung inflammation, thus enabling the surfactant to reduce edema and improve lung function, in experimental ARDS. Methods: ARDS was induced by cecal ligation and puncture surgery in BALB/c mice. A sham-operated group was used as control (CTRL). After surgery (6 hours), CTRL and ARDS animals were assigned to receive: (1) sterile saline solution; (2) LASSBio596; (3) exogenous surfactant or (4) LASSBio596 plus exogenous surfactant (n = 22/group). Results: Regardless of exogenous surfactant administration, LASSBio596 improved survival rate and