Simulated Aeromedical Evacuation Exacerbates Burn Induced Lung Injury: Targeting Mitochondrial DNA for Reversal

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background:</jats:bold> Aeromedical evacuation of patients with burn trauma is an important transport method at both wartime and peacetime, which exposes patients to prolonged periods of hypobaric hypoxia. However, the effects of such exposure on burn injury, particularly on burn induced lung injury are largely unexplored. The objective of this study is to investigate the effect of hypobaric hypoxia on burn induced lung injury and to discuss the possible mechanism by using a rat burn model. <jats:bold>Methods:</jats:bold> Male wistar rats inflicted with 30% total body surface area burn were exposed to hypobaric hypoxia condition (simulated 2000m altitude) or normoxia control for 24 h. Deoxyribonuclease I was systemically administrated as treatment intervention. Systemic inflammatory mediators and mitochondrial deoxyribonucleic acid level were detected. The histopathological examination, and acute lung injury score were determined. Malonaldehyde content, myeloperoxidase activity, and the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome level in the lung tissue were measured. Data among groups were compared by using analysis of variance followed by the post hoc analysis of Tukey's test. <jats:bold>Results:</jats:bold> Burn resulted in remarkably higher level of systemic inflammatory cytokines and mitochondrial deoxyribonucleic acid release, which was further heightened by hypobaric hypoxia exposure. Moreover, hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression, elevated malonaldehyde content and myeloperoxidase activity in the lung. Burn induced lung injury was exacerbated as shown by histopathological examination and acute lung injury score. Administration of deoxyribonuclease I markedly reduced mitochondrial deoxyribonucleic acid release and systemic inflammatory cytokines production. Furthermore, NLRP3 inflammasome level in the lung tissue was decreased and burn induced lung injury was ameliorated. <jats:bold>Conclusions:</jats:bold> Our results suggested that simulated aeromedical evacuation further increased the burn induced mitochondrial deoxyribonucleic acid release and exacerbated burn induced inflammation and lung injury. Deoxyribonuclease I reduced the release of mitochondrial deoxyribonucleic acid and limited the mitochondrial deoxyribonucleic acid-induced systemic inflammation, ameliorated burn-induced acute lung injury. Intervening mitochondrial deoxyribonucleic acid level could be a potential target to protect from burn-induced lung injury during aeromedical conditions and provide with safer air evacuations for severely burned patients.</jats:p>

Salvianolic Acid A Protects against Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Neutrophil NETosis

“…Sections were stained with hematoxylin and eosin (HE) after deparaffinization and observed under light microscopy. A histopathological semiquantitative score was independently conducted and assessed by two pathologists according to the criteria based on the alveolar congestion, hemorrhage, the existence of assembling with inflammatory cells, and the thickness of the alveolar walls [40,41]. Briefly, alveolar wall thickness, cellular infiltration, and hemorrhage were each scored from 0 (no injury) to 4 (maximal injury).…”