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In a rat model of Escherichia coli lipopolysaccharide-induced mild/moderate acute respiratory distress syndrome, a gradual PEEP increase (shorter adaptation time) effectively mitigated histological lung injury and biomarker release associated with lung inflammation, damage to epithelial cells, endothelial cells, and the extracellular matrix compared with an abrupt increase in PEEP. A more gradual PEEP increase (longer adaptation time) decreased lung damage, pulmonary vessel compression, and pulmonary arterial pressure.

Background Although bone marrow-derived mesenchymal stromal cells (BM-MSC) from patients with chronic obstructive pulmonary disease (COPD) appear to be phenotypically and functionally similar to BM-MSC from healthy sources in vitro, the impact of COPD on MSC metabolism and mitochondrial function has not been evaluated. In this study, we aimed to comparatively characterize MSC from healthy and emphysematous donors (H-MSC and E-MSC) in vitro and to assess therapeutic potential of these MSC and their EV (H-EV and E-EV) in an in vivo model of severe emphysema. Methods C57BL/6 mice received intratracheal porcine pancreatic elastase once weekly for 4 weeks to induce emphysema. Control animals received saline under the same protocol. Twenty-four hours after the last instillation, animals received saline, H-MSC, E-MSC, H-EV or E-EV intravenously. Results In vitro characterization demonstrated that E-MSC present downregulation of anti-inflammatory (TSG-6, VEGF, TGF-β and HGF) and antioxidant (CAT, SOD, Nrf2 and GSH) genes and their EV had larger median diameter and lower average concentration. Compared to H-MSC, E-MSC mitochondria also exhibited higher respiration rate, were morphologically elongated, expressed less dynamin-related protein-1, and produced more superoxide. When co-cultured with alveolar macrophages, both H-MSC and E-MSC induced an increase in iNOS and arginase-1 levels, but only H-MSC and their EV were able to enhance IL-10 levels. In vivo, emphysematous mice treated with E-MSC or E-EV demonstrated no amelioration in cardiorespiratory dysfunction. On the other hand, H-EVs, but not H-MSCs, improved lung inflammation and morphometry, as well as reduced pulmonary arterial hypertension and right ventricular dysfunction induced by severe emphysema. Based on these results, we also compared naive E-MSC and mitocepted E-MSC with H-MSC mitochondria (E-MSCMITO1:1), revealing that E-MSCMITO1:1 exhibited a higher respiration rate, an increase in gene expression of antioxidant mediators (CAT, SOD, Nrf2 and GSH-Px), mitofusin-2 and Miro1 (related to mitochondrial transfer) compared to naive E-MSC. Conclusion E-MSC and E-EV were unable to reverse cardiorespiratory dysfunction; however, E-MSC with mitochondrial reinforcement was found to have a more antioxidant profile and appears to benefit mitochondrial transfer more than naive E-MSC, suggesting a potential therapeutic approach that could potentiate the prognosis of autologous transplantation in severe COPD.

In experimental elastase-induced emphysema, mechanical ventilation with variable tidal volumes (VT) set to 30% coefficient of variation (CV) may result in more homogenous ventilation distribution, but might also impair right heart function. We hypothesized that a different CV setting could improve both lung and cardiovascular function. Therefore, we investigated the effects of different levels of VT variability on cardiorespiratory function, lung histology, and gene expression of biomarkers associated with inflammation, fibrogenesis, epithelial cell damage, and mechanical cell stress in this emphysema model. Wistar rats (n = 35) received repeated intratracheal instillation of porcine pancreatic elastase to induce emphysema. Seven animals were not ventilated and served as controls (NV). Twenty-eight animals were anesthetized and assigned to mechanical ventilation with a VT CV of 0% (BASELINE). After data collection, animals (n = 7/group) were randomly allocated to VT CVs of 0% (VV0); 15% (VV15); 22.5% (VV22.5); or 30% (VV30). In all groups, mean VT was 6 mL/kg and positive end-expiratory pressure was 3 cmH2O. Respiratory system mechanics and cardiac function (by echocardiography) were assessed continuously for 2 h (END). Lung histology and molecular biology were measured post-mortem. VV22.5 and VV30 decreased respiratory system elastance, while VV15 had no effect. VV0, VV15, and VV22.5, but not VV30, increased pulmonary acceleration time to pulmonary ejection time ratio. VV22.5 decreased the central moment of the mean linear intercept (D2 of Lm) while increasing the homogeneity index (1/β) compared to NV (77 ± 8 μm vs. 152 ± 45 μm; 0.85 ± 0.06 vs. 0.66 ± 0.13, p < 0.05 for both). Compared to NV, VV30 was associated with higher interleukin-6 expression. Cytokine-induced neutrophil chemoattractant-1 expression was higher in all groups, except VV22.5, compared to NV. IL-1β expression was lower in VV22.5 and VV30 compared to VV0. IL-10 expression was higher in VV22.5 than NV. Club cell protein 16 expression was higher in VV22.5 than VV0. SP-D expression was higher in VV30 than NV, while SP-C was higher in VV30 and VV22.5 than VV0. In conclusion, VV22.5 improved respiratory system elastance and homogeneity of airspace enlargement, mitigated inflammation and epithelial cell damage, while avoiding impairment of right cardiac function in experimental elastase-induced emphysema.

A dextran/fructose mixture was obtained by fermentation of a sucrose rich media using Leuconostoc mesenteroides NRRL B512(f). The dextran and fructose mixture obtained by fermentation as well as a synthetic mixture of pure components were separated using simulated moving bed (SMB) chromatography. In the case of the synthetic feed, the purity in the raffinate (dextran) and extract (fructose) was 96 and 81%, respectively. For the fermented mixture the purity values were 87.2% for the extract and 100% for the raffinate., (undefined)