Antithrombin plus alpha–1 protease inhibitor does not affect pulmonary inflammation and coagulation in a ‘double-hit’ lung injury model

Abstract Severe respiratory disorder induced by pulmonary inflammation is one of the causes of acute respiratory distress syndrome, which still has high mortality. It is crucial to remove causative substances and inflammatory mediators early in order to inhibit the progression of pulmonary inflammation. Total alveolar lavage (TAL) may avert the inflammatory response by eliminating causative substances in certain inflammatory lung diseases. We developed an efficient TAL system and examined the efficacy of short-term TAL treatment performed for acute lung injury models of rats. In the first experiment with a severe lung injury model, 15 rats were divided into 3 groups: sham group, mechanical gas ventilation (MGV) treatment group, and TAL treatment group. The treatments were conducted for 5 min, 20 min after the provocation of inflammation. Two days after treatment, the TAL and MGV treatment groups exhibited significant differences in blood oxygen levels, mean arterial pressure, weight-loss ratio, and inflammatory cytokine levels in the lungs. In contrast, almost no differences were observed between the TAL treatment and sham groups. In the second experiment with a lethal lung injury model, the TAL treatment dramatically improved the survival rate of the rats compared to the MGV treatment groups (p = 0.0079). Histopathological analysis confirmed pronounced differences in neutrophil accumulation and thickening of the interstitial membrane between the TAL and MGV treatment groups in both experiments. These results indicate that as little as 5 min of TAL treatment can protect rats from acute lung injury by removing causative substances from the lungs.

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Alkaline phosphatase in pulmonary inflammation—a translational study in ventilated critically ill patients and rats

Intensive Care Medicine Experimental ◽

10.1186/s40635-020-00335-x ◽

2020 ◽

Vol 8 (S1) ◽

Author(s):

Jenny Juschten ◽

◽

Sarah A. Ingelse ◽

Lieuwe D. J. Bos ◽

Armand R. J. Girbes ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Lung Injury ◽

Critically Ill ◽

Inflammatory Mediators ◽

Critically Ill Patients ◽

Pulmonary Inflammation ◽

Markers Of Inflammation ◽

Injury Model ◽

Lung Injury Model ◽

Epithelial Dysfunction

Abstract Background Alkaline phosphatase (AP), a dephosphorylating enzyme, is involved in various physiological processes and has been shown to have anti-inflammatory effects. Aim To determine the correlation between pulmonary AP activity and markers of inflammation in invasively ventilated critically ill patients with or without acute respiratory distress syndrome (ARDS), and to investigate the effect of administration of recombinant AP on pulmonary inflammation in a well-established lung injury model in rats Methods AP activity was determined and compared with levels of various inflammatory mediators in bronchoalveolar lavage fluid (BALF) samples obtained from critically ill patients within 2 days of start of invasive ventilation. The endpoints of this part of the study were the correlations between AP activity and markers of inflammation, i.e., interleukin (IL)-6 levels in BALF. In RccHan Wistar rats, lung injury was induced by intravenous administration of 10 mg/kg lipopolysaccharide, followed by ventilation with a high tidal volume for 4 h. Rats received either an intravenous bolus of 1500 IU/kg recombinant AP or normal saline 2 h after intravenous LPS administration, right before start of ventilation. Endpoints of this part of the study were pulmonary levels of markers of inflammation, including IL-6, and markers of endothelial and epithelial dysfunction. Results BALF was collected from 83 patients; 10 patients had mild ARDS, and 15 had moderate to severe ARDS. AP activity correlated well with levels of IL-6 (r = 0.70), as well as with levels of other inflammatory mediators. Pulmonary AP activity between patients with and without ARDS was comparable (0.33 [0.14–1.20] vs 0.55 [0.21–1.42] U/L; p = 0.37). Animals with acute lung injury had markedly elevated pulmonary AP activity compared to healthy controls (2.58 [2.18–3.59] vs 1.01 [0.80–1.46] U/L; p < 0.01). Intravenous administration of recombinant AP did neither affect pulmonary inflammation nor endothelial and epithelial dysfunction. Conclusions In ventilated critically ill patients, pulmonary AP activity correlates well with markers of pulmonary inflammation, such as IL-6 and IL-8. In animals with lung injury, pulmonary AP activity is elevated. Administration of recombinant AP does not alter pulmonary inflammation and endothelial or epithelial dysfunction in the acute phase of a murine lung injury model.

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Modulation of LPS-Stimulated Pulmonary Inflammation by Borneol in Murine Acute Lung Injury Model

Inflammation ◽

10.1007/s10753-014-9839-8 ◽

2014 ◽

Vol 37 (4) ◽

pp. 1148-1157 ◽

Cited By ~ 32

Author(s):

Weiting Zhong ◽

Yiwen Cui ◽

Qinlei Yu ◽

Xianxing Xie ◽

Yan Liu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Pulmonary Inflammation ◽

Injury Model ◽

Lung Injury Model

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Dynamic single-slice CT estimates whole-lung dual-energy CT variables in pigs with and without experimental lung injury

Intensive Care Medicine Experimental ◽

10.1186/s40635-019-0273-y ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 1

Author(s):

John N. Cronin ◽

João Batista Borges ◽

Douglas C. Crockett ◽

Andrew D. Farmery ◽

Göran Hedenstierna ◽

...

Keyword(s):

Lung Injury ◽

Dual Energy ◽

Dual Energy Ct ◽

Lung Density ◽

Density Distributions ◽

Single Slice ◽

Injury Model ◽

Lung Injury Model ◽

Ct Density ◽

Surfactant Depletion

Abstract Background Dynamic single-slice CT (dCT) is increasingly used to examine the intra-tidal, physiological variation in aeration and lung density in experimental lung injury. The ability of dCT to predict whole-lung values is unclear, especially for dual-energy CT (DECT) variables. Additionally, the effect of inspiration-related lung movement on CT variables has not yet been quantified. Methods Eight domestic pigs were studied under general anaesthesia, including four following saline-lavage surfactant depletion (lung injury model). DECT, dCT and whole-lung images were collected at 12 ventilatory settings. Whole-lung single energy scans images were collected during expiratory and inspiratory apnoeas at positive end-expiratory pressures from 0 to 20 cmH2O. Means and distributions of CT variables were calculated for both dCT and whole-lung images. The cranio-caudal displacement of the anatomical slice was measured from whole-lung images. Results Mean CT density and volume fractions of soft tissue, gas, iodinated blood, atelectasis, poor aeration, normal aeration and overdistension correlated between dCT and the whole lung (r2 0.75–0.94) with agreement between CT density distributions (r 0.89–0.97). Inspiration increased the matching between dCT and whole-lung values and was associated with a movement of 32% (SD 15%) of the imaged slice out of the scanner field-of-view. This effect introduced an artefactual increase in dCT mean CT density during inspiration, opposite to that caused by the underlying physiology. Conclusions Overall, dCT closely approximates whole-lung aeration and density. This approximation is improved by inspiration where a decrease in CT density and atelectasis can be interpreted as physiological rather than artefactual.

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