Transmigration and activation of neutrophils in the lung reflect key steps in the progression of acute lung injury (ALI). It is known that hydrogen sulfide (H₂S) can limit neutrophil activation, but the respective mechanisms remain elusive. Here, we aimed to examine the underlying pathways in pulmonary inflammation. In vivo, C57BL/6N mice received the H₂S slow releasing compound GYY4137 prior to lipopolysaccharide (LPS) inhalation. LPS challenge led to pulmonary injury, inflammation, and neutrophil transmigration that were inhibited in response to H₂S pretreatment. Moreover, H₂S reduced mRNA expression of macrophage inflammatory protein-2 (MIP-2) and its receptor in lung tissue, as well as the accumulation of MIP-2 and interleukin-1β in the alveolar space. In vitro, GYY4137 did not exert toxic effects on Hoxb8 neutrophils, but prevented their transmigration through an endothelial barrier in the presence and absence of MIP-2. In addition, the release of MIP-2 and reactive oxygen species from LPS-stimulated Hoxb8 neutrophils were directly inhibited by H₂S. Taken together, we provide first evidence that H₂S limits lung neutrophil sequestration upon LPS challenge. As proposed underlying mechanisms, H₂S prevents neutrophil transmigration through the inflamed endothelium and directly inhibits pro-inflammatory as well as oxidative signalling in neutrophils. Subsequently, H₂S pretreatment ameliorates LPS-induced ALI.

For the surveillance of transmissible spongiform encephalopathies (TSEs) in animals and humans, the discrimination of different TSE strains causing scrapie, BSE, or Creutzfeldt-Jakob disease constitutes a substantial challenge. We addressed this problem by Fourier transform-infrared (FT-IR) spectroscopy of pathological prion protein PrP27–30. Different isolates of hamster-adapted scrapie (263K, 22A-H, and ME7-H) and BSE (BSE-H) were passaged in Syrian hamsters. Two of these agents, 22A-H and ME7-H, caused TSEs with indistinguishable clinical symptoms, neuropathological changes, and electrophoretic mobilities and glycosylation patterns of PrP27–30. However, FT-IR spectroscopy revealed that PrP27–30 of all four isolates featured different characteristics in the secondary structure, allowing a clear distinction between the passaged TSE agents. FT-IR analysis showed that phenotypic information is mirrored in β-sheet and other secondary structure elements of PrP27–30, also in cases where immunobiochemical typing failed to detect structural differences. If the findings of this study hold true for nonexperimental TSEs in animals and humans, FT-IR characterization of PrP27–30 may provide a versatile tool for molecular strain typing without antibodies and without restrictions to specific TSEs or mammalian species.

In contrast to conventional mandatory ventilation, a new ventilation mode, expiratory ventilation assistance (EVA), linearises the expiratory tracheal pressure decline. We hypothesised that due to a recruiting effect, linearised expiration oxygenates better than volume controlled ventilation (VCV). We compared the EVA with VCV mode with regard to gas exchange, ventilation volumes and pressures and lung aeration in a model of peri-operative mandatory ventilation in healthy pigs. Controlled interventional trial. Animal operating facility at a university medical centre. A total of 16 German Landrace hybrid pigs. The lungs of anaesthetised pigs were ventilated with the EVA mode (n=9) or VCV (control, n=7) for 5 h with positive end-expiratory pressure of 5 cmH2O and tidal volume of 8 ml kg−1. The respiratory rate was adjusted for a target end-tidal CO2 of 4.7 to 6 kPa. Tracheal pressure, minute volume and arterial blood gases were recorded repeatedly. Computed thoracic tomography was performed to quantify the percentages of normally and poorly aerated lung tissue. Two animals in the EVA group were excluded due to unstable ventilation (n=1) or unstable FiO2 delivery (n=1). Mean tracheal pressure and P aO2 were higher in the EVA group compared with control (mean tracheal pressure: 11.6 ± 0.4 versus 9.0 ± 0.3 cmH2O, P < 0.001 and P aO2: 19.2 ± 0.7 versus 17.5 ± 0.4 kPa, P = 0.002) with comparable peak inspiratory tracheal pressure (18.3 ± 0.9 versus 18.0 ± 1.2 cmH2O, P > 0.99). Minute volume was lower in the EVA group compared with control (5.5 ± 0.2 versus 7.0 ± 1.0 l min−1, P = 0.02) with normoventilation in both groups (P aCO2 5.4 ± 0.3 versus 5.5 ± 0.3 kPa, P > 0.99). In the EVA group, the percentage of normally aerated lung tissue was higher (81.0 ± 3.6 versus 75.8 ± 3.0%, P = 0.017) and of poorly aerated lung tissue lower (9.5 ± 3.3 versus 15.7 ± 3.5%, P = 0.002) compared with control. EVA ventilation improves lung aeration via elevated mean tracheal pressure and consequently improves arterial oxygenation at unaltered positive end-expiratory pressure (PEEP) and peak inspiratory pressure (PIP). These findings suggest the EVA mode is a new approach for protective lung ventilation.

Local pulmonary and systemic infections can lead to acute lung injury (ALI). The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality. Hydrogen sulfide (H2S) appears to represent a new therapeutic approach to ALI. The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo. This study was designed to define its potentially protective role in sepsis-induced lung injury.