Background: Prolonged controlled mechanical ventilation depresses diaphragmatic efficiency. Assisted modes of ventilation should improve it. We assessed the impact of pressure support ventilation versus neurally adjusted ventilator assist on diaphragmatic efficiency. Method: Patients previously ventilated with controlled mechanical ventilation for 72 hours or more were randomized to be ventilated for 48 hours with pressure support ventilation (n =12) or neurally adjusted ventilatory assist (n = 13). Neuro-ventilatory efficiency (tidal volume/diaphragmatic electrical activity) and neuro-mechanical efficiency (pressure generated against the occluded airways/diaphragmatic electrical activity) were measured during three spontaneous breathing trials (0, 24 and 48 hours). Breathing pattern, diaphragmatic electrical activity and pressure time product of the diaphragm were assessed every 4 hours. Results: In patients randomized to neurally adjusted ventilator assist, neuro-ventilatory efficiency increased from 27 ± 19 ml/μV at baseline to 62 ± 30 ml/μV at 48 hours (p <0.0001) and neuro-mechanical efficiency increased from 1 ± 0.6 to 2.6 ± 1.1 cmH₂O/μV (p = 0.033). In patients randomized to pressure support ventilation, these did not change. Electrical activity of the diaphragm, neural inspiratory time, pressure time product of the diaphragm and variability of the breathing pattern were significantly higher in patients ventilated with neurally adjusted ventilatory assist. The asynchrony index was 9.48 [6.38– 21.73] in patients ventilated with pressure support ventilation and 5.39 [3.78– 8.36] in patients ventilated with neurally adjusted ventilatory assist (p = 0.04). Conclusion: After prolonged controlled mechanical ventilation, neurally adjusted ventilator assist improves diaphragm efficiency whereas pressure support ventilation does not. Trial registration: ClinicalTrials.gov study registration: NCT0247317, 06/11/2015.

Objective—To compare the effect of 2 concentrations of oxygen in inspired gas (fraction of inspired oxygen [FIO₂] 1.0 or 0.4) on pulmonary aeration and gas exchange in dogs during inhalation anesthesia. Animals—20 healthy dogs. Procedures—Following administration of acepromazine and morphine, anesthesia was induced in each dog with thiopental and maintained with isoflurane in 100% oxygen (100% group; n = 10) or a mixture of 40% oxygen and air (40% group; 10). Dogs were placed in dorsal recumbency and were mechanically ventilated. After surgery, spiral computed tomography (CT) of the thorax was performed and PaO₂, PaCO₂, and the alveolar-arterial oxygen tension difference (P_[A–a]O₂) were assessed. The lung CT images were analyzed, and the extent of hyperinflated (−1,000 to −901 Hounsfield units [HUs]), normally aerated (−900 to −501 HUs), poorly aerated (−500 to −101 HUs), or nonaerated (−100 to +100 HUs) areas was determined. Results—Compared with the 100% oxygen group, the normally aerated lung area was significantly greater and the poorly aerated and nonaerated areas were significantly smaller in the 40% oxygen group. The time to CT (duration of surgery) was similar in both groups. Although PaCO₂ was similar in both groups, PaO₂ and P_(A–a)O₂ were significantly higher in the 100% oxygen group. In both groups, pulmonary atelectasis developed preferentially in caudal lung fields. Conclusion and Clinical Relevance—In isoflurane-anesthetized dogs, mechanical ventilation with 40% oxygen appeared to maintain significantly better lung aeration and gas exchange than ventilation with 100% oxygen.

Rationale: The open lung strategy aims at reopening (recruitment) of nonaerated lung areas in patients with acute respiratory distress syndrome, avoiding tidal alveolar hyperinflation in the limited area of normally aerated tissue (baby lung). Objectives: We tested the hypothesis that recruited lung areas do not resume elastic properties of adjacent baby lung. Methods: Twenty-five anesthetized, mechanically ventilated pigs were studied. Four lung-healthy pigs served as controls and the remaining 21 were divided into three groups (n = 7 each) in which lung injury was produced by surfactant lavage, lipopolysaccharide infusion, or hydrochloride inhalation. Computed tomography scans, respiratory mechanics, and gas exchange parameters were recorded under three conditions: at baseline, during lung recruitment maneuver, and at end-expiration and end-inspiration when ventilating after an open lung protocol. Measurements and Main Results: During recruitment maneuver and open lung protocol, the gas volume entering the insufficiently aerated compartment was 96% (75–117%) and 48% (41–63%) (median [interquartile range]) of the functional residual capacity measured before and at zero end-expiratory pressure, respectively. Nonetheless, the volume of hyperinflated lung increased during both recruitment maneuver (by 1–28% of total lung volume; P < 0.01) and open lung protocol ventilation at end-inspiration (by 1–15% of total lung volume; P < 0.01). Regional elastance of recruited lung tissue was consistently higher than that of the baby lung regardless of the ARDS model (P < 0.01). Conclusions: Alveolar recruitment is not protective against hyperinflation of the baby lung because lung parenchyma is inhomogeneous during ventilation with the open lung strategy.

Increasing evidence demonstrates a phenotypic plasticity of endothelial cells (ECs). Endothelial-to-mesenchymal transition (EndMT) contributes to the development of tissue fibrosis. However, the pathogenic factors and signalling pathways regulating this process in ischaemia/reperfusion (I/R) injury are still poorly understood. We investigated the possible role of complement in the induction of this endothelial dysfunction in a swine model of renal I/R injury by using recombinant C1 inhibitor in vivo. Here, we showed that I/R injury reduced the density of renal peritubular capillaries and induced tissue fibrosis with generation of CD31⁺/α-SMA⁺ and CD31⁺/FPS-1⁺ cells indicating EndMT. When we inhibited complement, the process of EndMT became rare, with preserved density of peritubular capillaries and significant reduction in renal fibrosis. When we activated ECs by anaphylatoxins in vitro, C3a and C5a led to altered endothelial phenotype with increased expression of fibroblast markers and decrease expression of specific endothelial markers. The activation of Akt pathway was pivotal for the C3a and C5a-induced EndMT in vitro. In accordance, inhibition of complement in vivo led to the abrogation of Akt signalling, with hampered EndMT and tissue fibrosis. Our data demonstrate a critical role for complement in the acute induction of EndMT via the Akt pathway. Therapeutic inhibition of these systems may be essential to prevent vascular damage and tissue fibrosis in transplanted kidney.