Evaluation of Respiratory System Mechanics in Mice using the Forced Oscillation Technique

McGovern, Toby K.; Robichaud, Annette; Fereydoonzad, Liah; Schuessler, Thomas F.; Martin, James G.

doi:10.3791/50172-v

Cited by 14 publications

(12 citation statements)

References 7 publications

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“…Lung mechanics such as lung resistance, lung compliance, and tissue elastance were measured in anesthetized mice. Mice were mechanically ventilated with a tidal volume of 10 ml/kg and a positive end-expiratory pressure of 2 cm H 2 O using the flexiVent (Scireq, Montreal, QC, Canada) ventilation setup as previously described in McGovern et al (30).…”

Section: Measurement Of Lung Mechanicsmentioning

confidence: 99%

Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury

2019

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Adiponectin (APN), an adipocyte-derived adipokine, has been shown to limit lung injury originating from endothelial cell (EC) damage. Previously we reported that obese mice with low circulatory APN levels exhibited pulmonary vascular endothelial dysfunction. This study was designed to investigate the cellular and molecular mechanisms underlying the pulmonary endothelium-dependent protective effects of APN. Our results demonstrated that in APN 2/2 mice, there was an inherent state of endothelium mitochondrial dysfunction that could contribute to endothelial activation and increased susceptibility to LPS-induced acute lung injury (ALI). We noted that APN 2/2 mice showed decreased expression of mitochondrial biogenesis regulatory protein peroxisome proliferator-activated receptor g coactivator 1-a (PGC-1a) and its downstream proteins nuclear respiratory factor 1, transcription factor A, mitochondrial, and Sirtuin (Sirt)3 and Sirt1 expression in whole lungs and in freshly isolated lung ECs from these mice at baseline and subjected to LPS-induced ALI. We further showed that treating APN 2/2 mice with PGC-1a activator pyrroloquinoline quinone enhances mitochondrial biogenesis and function in lung endothelium and attenuation of ALI. These results suggest that the pulmonary endothelium-protective properties of APN are mediated, at least in part, by an enhancement of mitochondrial biogenesis through a mechanism involving PGC-1a activation.-Shah, D., Torres, C., Bhandari, V. Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury.

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Section: Measurement Of Lung Mechanicsmentioning

confidence: 99%

Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury

2019

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“…Lung function assessments were conducted using a flexiVent® mechanical respirator (flexiVent®, SCIREQ, Montreal, PQ, Canada) according to SCIREQ Scientific Respiratory Equipment Inc.'s published protocols 49 . FlexiVent® enabled the measurement of lung elastance which is a functional parameter derived from the pressure‐driven pressure–volume loops.…”

Section: Methodsmentioning

confidence: 99%

Myeloid‐specific deletion of activating transcription factor 6 alpha increases CD11b⁺ macrophage subpopulations and aggravates lung fibrosis

et al. 2023

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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease of unknown etiology. The accumulation of macrophages is associated with disease pathogenesis. The unfolded protein response (UPR) has been linked to macrophage activation in pulmonary fibrosis. To date, the impact of activating transcription factor 6 alpha (ATF6α), one of the UPR mediators, on the composition and function of pulmonary macrophage subpopulations during lung injury and fibrogenesis is not fully understood. We began by examining the expression of Atf6α in IPF patients’ lung single‐cell RNA sequencing dataset, archived surgical lung specimens, and CD14+ circulating monocytes. To assess the impact of ATF6α on pulmonary macrophage composition and pro‐fibrotic function during tissue remodeling, we conducted an in vivo myeloid‐specific deletion of Atf6α. Flow cytometric assessments of pulmonary macrophages were carried out in C57BL/6 and myeloid specific ATF6α‐deficient mice in the context of bleomycin‐induced lung injury. Our results demonstrated that Atf6α mRNA was expressed in pro‐fibrotic macrophages found in the lung of a patient with IPF and in CD14+ circulating monocytes obtained from blood of a patient with IPF. After bleomycin administration, the myeloid‐specific deletion of Atf6α altered the pulmonary macrophage composition, expanding CD11b+ subpopulations with dual polarized CD38+CD206+ expressing macrophages. Compositional changes were associated with an aggravation of fibrogenesis including increased myofibroblast and collagen deposition. A further mechanistic ex vivo investigation revealed that ATF6α was required for CHOP induction and the death of bone marrow‐derived macrophages. Overall, our findings suggest a detrimental role for the ATF6α‐deficient CD11b+ macrophages which had altered function during lung injury and fibrosis.

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“…Ventilation studies were performed using flexiVent (SCIREQ Inc.). FlexiVent is a murine ventilation system based on the linear single‐frequency forced oscillation technique (FOT), as previously described 10,11 . This FOT system was used to determine inspiratory capacity (IC) and large airway resistance in CDH and control rodents.…”

Section: Methodsmentioning

confidence: 99%

“…FlexiVent is a murine ventilation system based on the linear single-frequency forced oscillation technique (FOT), as previously described. 10,11 This FOT system was used to determine inspiratory capacity (IC) and large airway resistance in CDH and control rodents. Newborn pups were anesthetized with inhalational isoflurane (4%; Clipper Distributing Company, LLC).…”

Section: Oxygenation and Ventilation Datamentioning

confidence: 99%

Neonatal rodent ventilation and clinical correlation in congenital diaphragmatic hernia

Gupta

Wilson

Popp

et al. 2022

Pediatric Pulmonology

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Introduction Ventilator management is a critical part of managing congenital diaphragmatic hernia (CDH). We aimed to use a murine model and patient data to study CDH‐associated differences in oxygenation, airway resistance, and pulmonary mechanics by disease severity. Methods We used the nitrofen model of CDH. For control and CDH rodents, data were collected within the first hour of life. Oxygen saturations (SpO2) were collected using MouseOx, and large airway resistance and inspiratory capacities were collected using flexiVent. A single‐center, retrospective review of term CDH infants from 2014 to 2020 was performed. Tidal volumes were collected every 6 h for the first 48 h of life or until the patient was taken off conventional ventilation. Newborns that were mechanically ventilated but had no pulmonary pathology were used as controls. CDH severity was defined using the CDH Study Group (CDHSG) classification system. Results Control rodents had a median SpO2 of 94% (IQR: 88%–98%); CDH pups had a median SpO2 of 27.9% (IQR: 22%–30%) (p < 0.01). CDH rodents had lower inspiratory capacity than controls (median: 110 μl, IQR: 70–170 vs. median: 267 μl, IQR: 216–352; p < 0.01). CDH infants had a lower initial SpO2 than control infants. Overall, CDH infants had lower tidal volumes than control infants (median: 4.2 ml/kg, IQR: 3.3–5.0 vs. 5.4 ml/kg, IQR: 4.7–6.2; p = 0.03). Tidal volumes varied by CDHSG stage. Conclusion Newborns with CDH have lower SpO2 and lower, CDHSG stage specific, tidal volumes than control infants. The nitrofen model of CDH reflects these differences. Rodent models may be useful in studying therapeutic ventilatory strategies for CDH infants.

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Evaluation of Respiratory System Mechanics in Mice using the Forced Oscillation Technique

Cited by 14 publications

References 7 publications

Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury

Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury

Myeloid‐specific deletion of activating transcription factor 6 alpha increases CD11b⁺ macrophage subpopulations and aggravates lung fibrosis

Neonatal rodent ventilation and clinical correlation in congenital diaphragmatic hernia

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Evaluation of Respiratory System Mechanics in Mice using the Forced Oscillation Technique

Cited by 14 publications

References 7 publications

Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury

Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury

Myeloid‐specific deletion of activating transcription factor 6 alpha increases CD11b+ macrophage subpopulations and aggravates lung fibrosis

Neonatal rodent ventilation and clinical correlation in congenital diaphragmatic hernia

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Myeloid‐specific deletion of activating transcription factor 6 alpha increases CD11b⁺ macrophage subpopulations and aggravates lung fibrosis