Ventilator-induced lung-injury in mouse models: Is there a trap?

Joelsson, Jon Pétur; Ingþórsson, Sævar; Kricker, Jennifer A.; Guðjónsson, Þórarinn; Kárason, Sigurbergur

doi:10.1186/s42826-021-00108-x

Cited by 13 publications

(11 citation statements)

References 117 publications

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“…Mouse models of VILI have shown that overstretching the lung tissues increases the inflammatory response in mice along with damaging the lung epithelium [ 3 ]. Setting up our own mouse model of VILI, we set out to identify important genes involved in the transcriptional response to mechanical ventilation of different tidal volumes.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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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Section: Discussionmentioning

confidence: 99%

“…The four main hallmarks of VILI have traditionally been baro/volutrauma, atelectrauma, oxygen toxicity and biotrauma [ 3 ]. Baro/volutrauma occurs when using inappropriately high airway pressures or tidal volumes subjecting open alveoli to over-distension.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…This must be considered in the selection of a mouse ARDS model. As shown in Table 1 , models directly linked to lung damage use intratracheal or intranasal application of lipopolysaccharide (LPS) or bacteria, intratracheal instillation of acids or bleomycin, 100% O 2 and mechanical ventilation (MV) [ 18 ], or pulmonary ischemia/reperfusion injury. Whereas the last-mentioned intervention requires surgery, all the other methods depend on intranasal or intratracheal application, which is easier to achieve.…”

Section: Methodsmentioning

confidence: 99%

Antioxidants as Therapeutic Agents in Acute Respiratory Distress Syndrome (ARDS) Treatment—From Mice to Men

et al. 2022

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Acute respiratory distress syndrome (ARDS) is a major cause of patient mortality in intensive care units (ICUs) worldwide. Considering that no causative treatment but only symptomatic care is available, it is obvious that there is a high unmet medical need for a new therapeutic concept. One reason for a missing etiologic therapy strategy is the multifactorial origin of ARDS, which leads to a large heterogeneity of patients. This review summarizes the various kinds of ARDS onset with a special focus on the role of reactive oxygen species (ROS), which are generally linked to ARDS development and progression. Taking a closer look at the data which already have been established in mouse models, this review finally proposes the translation of these results on successful antioxidant use in a personalized approach to the ICU patient as a potential adjuvant to standard ARDS treatment.

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“…The EIT measurement was undertaken during the following ventilator maneuver: An initial respiratory rate set at 120 breaths/min and positive end-expiratory pressure of 5 cm H 2 O ( Basoalto, et al, 2021 ; Ferrini, et al, 2021 ; Joelsson et al, 2021 ). Over 120 s, PIP was increased from 10 to 35 cm H 2 O in 5 cm H 2 O increments (stepwise inflation) and thereafter returned in 5 cm H 2 O steps back to the baseline (stepwise deflation).…”

Section: Methodsmentioning

confidence: 99%

Surfactant Treatment Shows Higher Correlation Between Ventilator and EIT Tidal Volumes in an RDS Animal Model

Kim

Choi

et al. 2022

Front. Physiol.

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Neonatal respiratory distress syndrome (RDS) is a condition of pulmonary surfactant insufficiency in the premature newborn. As such, artificial pulmonary surfactant administration is a key treatment. Despite continued improvement in the clinical outcomes of RDS, there are currently no established bedside tools to monitor whether pulmonary surfactant is effectively instilled throughout the lungs. Electrical impedance tomography (EIT) is an emerging technique in which physiological functions are monitored on the basis of temporal changes in conductivity of different tissues in the body. In this preliminary study, we aimed to assess how EIT tidal volumes correlate with ventilator tidal volumes in an RDS animal model, namely untreated, surfactant-treated, and normal control rabbit pups. Tidal volumes were measured simultaneously on an EIT system and a mechanical ventilator and compared at different peak inspiratory pressures. The linear correlation between tidal volumes measured by EIT and by ventilator had an R2 of 0.71, 0.76 and 0.86 in the untreated, surfactant-treated, and normal control groups, respectively. Bland–Altman analysis showed a good correlation between the measurements obtained with these two modalities. The intraclass correlation coefficients (ICC) between ventilator tidal volume and EIT tidal volume were 0.83, 0.87, and 0.93 (all p < 0.001) in the untreated, surfactant-treated, and normal control groups, respectively, indicating that the higher ICC value, the better inflated status of the lung. In conclusion, we demonstrated that EIT tidal volume correlated with ventilator tidal volume. ICC was higher in the surfactant treated group.

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Ventilator-induced lung-injury in mouse models: Is there a trap?

Cited by 13 publications

References 117 publications

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

Antioxidants as Therapeutic Agents in Acute Respiratory Distress Syndrome (ARDS) Treatment—From Mice to Men

Surfactant Treatment Shows Higher Correlation Between Ventilator and EIT Tidal Volumes in an RDS Animal Model

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