Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury

Albert, Karolin; Krischer, Jeanne-Marie; Pfaffenroth, Alexander; Wilde, Sabrina; López-Rodríguez, Elena; Braun, Armin; Smith, Bradford J.; Knudsen, Lars

doi:10.3389/fphys.2020.530485

Cited by 17 publications

(20 citation statements)

References 57 publications

(107 reference statements)

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“…Tissue elastance H, based on impedance data from forced oscillation perturbations at the conclusion of the mechanical ventilation demonstrated a positive correlation with the volume of electronlucent multivesicular bodies (d). The tissue elastance data shown in d were taken from a previous publication (Albert et al 2020). The Pearson correlation coefficient r and statistical significant p are given.…”

Section: Discussionmentioning

confidence: 99%

“…After randomization, male rats (Fisher 344/DuCrl, Charles River, Sulzfeld, Germany) were either treated intratracheally with Bleomycin (Group B; Dosage: 4.5 U/kg bodyweight, n = 20) or not (Group H,healthy,n = 17). This dosage of Bleomycin has been shown to result in subclinical lung injury at day 1, meaning that clinical presentation, oxygen saturation and tissue elastance measurements are not substantially different from healthy controls (Lutz et al 2015;Albert et al 2020). At day 1, animals were further randomized into three subgroups characterized by different mechanical ventilation protocols.…”

Section: Subjects and Study Designmentioning

confidence: 99%

“…8c). In our previous study we characterized the mechanical properties during mechanical ventilation and repetitively measured the tissue elastance by means of the forced oscillation perturbation (Albert et al 2020). The final measurements of tissue elastance, which was carried out during PEEP = 3 cmH 2 O ventilation were taken from that study for correlation with Fig.…”

Section: Correlation Analysesmentioning

confidence: 99%

“…Therefore, we opted to ventilate the lungs with PEEP = 1 cmH 2 O, where microatelectases are present, or at PEEP = 5 cmH 2 O, where microatelectases are nearly absent. Since mechanical ventilation of lungs suffering from microatelectases would induce alveolar overdistension due to alveolar interdependence (Albert et al 2019(Albert et al , 2020, we hypothesize that PEEP = 1 cmH 2 O ventilation of bleomycin-injured lungs will exhibit abnormalities of intracellular surfactant pool and interstitial abnormalities that demarcate injury progression within alveolar septa.…”

Section: Introductionmentioning

confidence: 99%

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Mechanical ventilation-induced alterations of intracellular surfactant pool and blood–gas barrier in healthy and pre-injured lungs

Krischer

Albert

Pfaffenroth

et al. 2020

Histochem Cell Biol

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Mechanical ventilation triggers the manifestation of lung injury and pre-injured lungs are more susceptible. Ventilation-induced abnormalities of alveolar surfactant are involved in injury progression. The effects of mechanical ventilation on the surfactant system might be different in healthy compared to pre-injured lungs. In the present study, we investigated the effects of different positive end-expiratory pressure (PEEP) ventilations on the structure of the blood–gas barrier, the ultrastructure of alveolar epithelial type II (AE2) cells and the intracellular surfactant pool (= lamellar bodies, LB). Rats were randomized into bleomycin-pre-injured or healthy control groups. One day later, rats were either not ventilated, or ventilated with PEEP = 1 or 5 cmH2O and a tidal volume of 10 ml/kg bodyweight for 3 h. Left lungs were subjected to design-based stereology, right lungs to measurements of surfactant proteins (SP−) B and C expression. In pre-injured lungs without ventilation, the expression of SP-C was reduced by bleomycin; while, there were fewer and larger LB compared to healthy lungs. PEEP = 1 cmH2O ventilation of bleomycin-injured lungs was linked with the thickest blood–gas barrier due to increased septal interstitial volumes. In healthy lungs, increasing PEEP levels reduced mean AE2 cell size and volume of LB per AE2 cell; while in pre-injured lungs, volumes of AE2 cells and LB per cell remained stable across PEEPs. Instead, in pre-injured lungs, increasing PEEP levels increased the number and decreased the mean size of LB. In conclusion, mechanical ventilation-induced alterations in LB ultrastructure differ between healthy and pre-injured lungs. PEEP = 1 cmH2O but not PEEP = 5 cmH2O ventilation aggravated septal interstitial abnormalities after bleomycin challenge.

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Section: Discussionmentioning

confidence: 99%

Section: Subjects and Study Designmentioning

confidence: 99%

Section: Correlation Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mechanical ventilation-induced alterations of intracellular surfactant pool and blood–gas barrier in healthy and pre-injured lungs

Krischer

Albert

Pfaffenroth

et al. 2020

Histochem Cell Biol

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“…b A stack of virtual, twodimensional images was generated using multi-photon microscopy to create a three-dimensional dataset. This lung was part of a study of ventilation-induced lung injury (Albert et al 2020), using intravenous administration of Evans blue which binds to albumin so that those areas suffering from vascular leakage could be identified (arrow). c A confocal microscopic image shows a 3D view of the lung parenchyma with alveolar epithelial type II cells labeled in red, cell nuclei in blue and septa in green.…”

Section: Prerequisites: Sampling Tissue Deformation Spatial Orientationmentioning

confidence: 99%

Stereology as the 3D tool to quantitate lung architecture

Knudsen

Brandenberger

Ochs

2020

Histochem Cell Biol

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Stereology is the method of choice for the quantitative assessment of biological objects in microscopy. It takes into account the fact that, in traditional microscopy such as conventional light and transmission electron microscopy, although one has to rely on measurements on nearly two-dimensional sections from fixed and embedded tissue samples, the quantitative data obtained by these measurements should characterize the real three-dimensional properties of the biological objects and not just their “flatland” appearance on the sections. Thus, three-dimensionality is a built-in property of stereological sampling and measurement tools. Stereology is, therefore, perfectly suited to be combined with 3D imaging techniques which cover a wide range of complementary sample sizes and resolutions, e.g. micro-computed tomography, confocal microscopy and volume electron microscopy. Here, we review those stereological principles that are of particular relevance for 3D imaging and provide an overview of applications of 3D imaging-based stereology to the lung in health and disease. The symbiosis of stereology and 3D imaging thus provides the unique opportunity for unbiased and comprehensive quantitative characterization of the three-dimensional architecture of the lung from macro to nano scale.

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Unifying Hypothesis of Ventilator-Induced Lung Injury

Nieman,

Habashi

2024

Applied Physiology to Reduce Ventilator Induced Lung Injury

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Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury

Cited by 17 publications

References 57 publications

Mechanical ventilation-induced alterations of intracellular surfactant pool and blood–gas barrier in healthy and pre-injured lungs

Mechanical ventilation-induced alterations of intracellular surfactant pool and blood–gas barrier in healthy and pre-injured lungs

Stereology as the 3D tool to quantitate lung architecture

Unifying Hypothesis of Ventilator-Induced Lung Injury

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