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Ventilator-induced lung injury results in oxidative stress response and mitochondrial swelling in a mouse model

Ventilator-induced lung injury results in oxidative stress response and mitochondrial swelling in a mouse model


Title: Ventilator-induced lung injury results in oxidative stress response and mitochondrial swelling in a mouse model
Author: Jóelsson, Jón Pétur
Ásbjarnarson, Árni
Sigurdsson, Snaevar   orcid.org/0000-0003-4860-6311
Kricker, Jennifer   orcid.org/0000-0002-0757-1936
Valdimarsdottir, Bryndis
Thorarinsdottir, Holmfridur
Starradottir, Eir
Gudjonsson, Thorarinn   orcid.org/0000-0001-9645-9665
Ingthorsson, Saevar   orcid.org/0000-0001-8480-9680
Kárason, Sigurbergur
Date: 2022-07-22
Language: English
Scope: 23
University/Institute: Landspitali - The National University Hospital of Iceland
Department: Faculty of Medicine
Perioperative Services
Series: Laboratory animal research; 38(1)
ISSN: 1738-6055
DOI: https://doi.org/10.1186/s42826-022-00133-4
Subject: Svæfinga- og gjörgæslulæknisfræði
URI: https://hdl.handle.net/20.500.11815/3496

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Citation:

Jóelsson , J P , Ásbjarnarson , Á , Sigurdsson , S , Kricker , J , Valdimarsdottir , B , Thorarinsdottir , H , Starradottir , E , Gudjonsson , T , Ingthorsson , S & Kárason , S 2022 , ' Ventilator-induced lung injury results in oxidative stress response and mitochondrial swelling in a mouse model ' , Laboratory animal research , vol. 38 , no. 1 , pp. 23 . https://doi.org/10.1186/s42826-022-00133-4

Abstract:

BACKGROUND: Mechanical ventilation is a life-saving therapy for critically ill patients, providing rest to the respiratory muscles and facilitating gas exchange in the lungs. Ventilator-induced lung injury (VILI) is an unfortunate side effect of mechanical ventilation that may lead to serious consequences for the patient and increase mortality. The four main injury mechanisms associated with VILI are: baro/volutrauma caused by overstretching the lung tissues; atelectrauma, caused by repeated opening and closing of the alveoli resulting in shear stress; oxygen toxicity due to use of high ratio of oxygen in inspired air, causing formation of free radicals; and biotrauma, the resulting biological response to tissue injury, that leads to a cascade of events due to excessive inflammatory reactions and may cause multi-organ failure. An often-overlooked part of the inflammatory reaction is oxidative stress. In this research, a mouse model of VILI was set up with three tidal volume settings (10, 20 and 30 mL/kg) at atmospheric oxygen level. Airway pressures and heart rate were monitored and bronchoalveolar lavage fluid (BALF) and lung tissue samples were taken. RESULTS: We show a correlation between increased inflammation and barrier failure, and higher tidal volumes, evidenced by increased IL-6 expression, high concentration of proteins in BALF along with changes in expression of adhesion molecules. Furthermore, swelling of mitochondria in alveolar type II cells was seen indicating their dysfunction and senescence-like state. RNA sequencing data present clear increases in inflammation, mitochondrial biogenesis and oxidative stress as tidal volume is increased, supported by degradation of Keap1, a redox-regulated substrate adaptor protein. CONCLUSIONS: Oxidative stress seems to be a more prominent mechanism of VILI than previously considered, indicating that possible treatment methods against VILI might be identified by impeding oxidative pathways.

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© 2022. The Author(s).

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