Evaluation of a simultaneous adsorption device for cytokines and platelet–neutrophil complexes in vitro and in a rabbit acute lung injury model

Background Platelet–neutrophil complexes (PNCs) readily migrate into tissues and induce tissue damage via cytokine or other pathogenic factors release. These actions are involved in onset and progression of acute respiratory distress syndrome (ARDS). Thus, simultaneous removal of cytokines and activated neutrophils, including PNCs by blood purification may prevent development of ARDS and enhance drug effects. The goal of this study was to examine the effect of a newly developed adsorption column (NOA-001) that eliminates cytokines and activated neutrophils in a lung injury model. Results Adsorption of cytokines, such as IL-8, IL-6 and HMGB-1, and PNCs was first measured in vitro. Lung injury was induced by HCl and lipopolysaccharide intratracheal infusion in rabbits ventilated at a low tidal volume (7–8 mL/kg) and PEEP (2.5 cmH2O) for lung protection. Arterial blood gas, hematologic values, plasma IL-8, blood pressure and heart rate were measured, and lung damage was evaluated histopathologically in animals treated with 8-h direct hemoperfusion with or without use of NOA-001. The in vitro adsorption rates for IL-8, IL-6, HMGB-1, activated granulocytes and PNCs were 99.5 (99.4–99.5)%, 63.9 (63.4–63.9)%, 57.6 (57.4–62.1)%, 9.9 (-4.4–21.3)% and 60.9 (49.0–67.6)%, respectively. Absorption of PNCs onto fibers was confirmed microscopically. These adsorption effects were associated with several improvements in the rabbit model. In respiratory function, the PaO2/FIO2 ratios at 8 h were 314 ± 55 mmHg in the NOA-001 group and 134 ± 41 mmHg in the sham group. The oxygenation index and PaCO2 at 8 h were 9.6 ± 3.1 and 57.0 ± 9.6 mmHg in the sham group and 3.0 ± 0.8 and 40.4 ± 4.5 mmHg in the NOA-001 group, respectively (p < 0.05). Blood pH at 8 h reached 7.18 ± 0.06 in the sham group, but was maintained at 7.36 ± 0.03 (within the normal range) in the NOA-001 group (p < 0.05). In lung histopathology, fewer hyaline membrane and inflammatory cells were observed in the NOA-001 group. Conclusion A column for simultaneous removal of cytokines and PNCs showed efficacy for improvement of pulmonary function in an animal model. This column may be effective in support of treatment of ARDS.

Penehyclidine Hydrochloride Has the Function of Lung Protection for Acute Lung Injury in Rat Models:A Systemic Review and Meta-analysis

ObjectiveThis systematic review and meta-analysis aims to review the effects of penehyclidine hydrochloride (PHC) on acute lung injury in animal models. MethodsPubMed, Embase, CNKI were searched for collecting the randomized controlled trials(RCTs) on the effects of penehyclidine hydrochloride on acute lung injury in rat models from inception to July 1, 2021. We used Cochrane evaluating quality and RevMan 5.3 software performing Meta-analysis.(lung W/D ratio、PaO2/FiO2、SOD、MPO activity、IL-6 and TNF-α) ResultsOur search including 11 studies in 3 databases. Meta-analysis showed that, Compared with the acute lung injury model group, the PHC treatment group: lung W/D ratio[MD=-1.29，95%CI（-1.94，-0.64），P＜0.01]、PaO2/FiO2[MD=1.73，95%CI（0.01，3.45），P＜0.01]、SOD[MD=7.05，95%CI（5.58，8.52），P＜0.000,01]、IL-6 [MD=-1.03，95%CI（-1.29，-0.77），P＜0.0001]、IL-6 [MD=-3.35，95%CI（-5.29，-1.40），P＜0.001]and TNF-α[MD=-2.17，95%CI（-3.27，-1.07），P＜0.0001].Conclusionspenehyclidine hydrochloride has the function of lung protection in acute lung injury and provides a new therapy for future clinical treatment.

Intrabronchial application of extracellular histones shows no proinflammatory effects in swine in a translational pilot study

Objective Extracellular histones have been identified as one molecular factor that can cause and sustain alveolar damage and were linked to high mortality rates in critically ill patients. In this pilot study, we wanted to validate the proinflammatory in vivo effects of local histone application in a prospective translational porcine model. This was combined with the evaluation of an experimental acute lung injury model using intrabronchial lipopolysaccharides, which has been published previously. Results The targeted application of histones was successful in all animals. Animals showed decreased oxygenation after instillation, but no differences could be detected between the sham and histone treatments. The histologic analyses and inflammatory responses indicated that there were no differences in tissue damage between the groups.

Resveratrol-Loaded Lipid-Core Nanocapsules Modulate Acute Lung Inflammation and Oxidative Imbalance Induced by LPS in Mice

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are inflammatory and oxidative imbalance lung conditions with no successful pharmacological therapy and a high mortality rate. Resveratrol (RSV) is a plant-derived stilbene that presents anti-inflammatory and antioxidant effects. However, its therapeutic application remains limited due to its poor bioavailability, which can be solved by the use of nanocarriers. Previously, we demonstrated that nanoencapsulated RSV (RSV-LNC) pre-treatment, performed 4 h before lipopolysaccharide (LPS) stimulation in mice, increased its anti-inflammatory properties. In this study, we evaluated the anti-inflammatory and antioxidant effects, and lung distribution of RSV-LNCs administered therapeutically (6 h post LPS exposure) in a lung injury mouse model. The results showed that RSV-LNCs posttreatment improved lung function and diminished pulmonary inflammation. Moreover, RSV-LNC treatment enhanced the antioxidant catalase level together with a decrease in the oxidative biomarker in mouse lungs, which was accompanied by an increase in pulmonary Nrf2 antioxidant expression. Finally, the presence of RSV in lung tissue was significantly detected when mice received RSV-LNCs but not when they received RSV in its free form. Together, our results confirm that RSV nanoencapsulation promotes an increase in RSV bioavailability, enhancing its therapeutic effects in an LPS-induced lung injury model.