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Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury
Mechanical ventilation of lungs suffering from microatelectases may trigger the development of acute lung injury (ALI). Direct lung injury by bleomycin results in surfactant dysfunction and microatelectases at day 1 while tissue elastance and oxygenation remain normal. Computational simulations of a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530907/ https://www.ncbi.nlm.nih.gov/pubmed/33071807 http://dx.doi.org/10.3389/fphys.2020.530485 |
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author | Albert, Karolin Krischer, Jeanne-Marie Pfaffenroth, Alexander Wilde, Sabrina Lopez-Rodriguez, Elena Braun, Armin Smith, Bradford J. Knudsen, Lars |
author_facet | Albert, Karolin Krischer, Jeanne-Marie Pfaffenroth, Alexander Wilde, Sabrina Lopez-Rodriguez, Elena Braun, Armin Smith, Bradford J. Knudsen, Lars |
author_sort | Albert, Karolin |
collection | PubMed |
description | Mechanical ventilation of lungs suffering from microatelectases may trigger the development of acute lung injury (ALI). Direct lung injury by bleomycin results in surfactant dysfunction and microatelectases at day 1 while tissue elastance and oxygenation remain normal. Computational simulations of alveolar micromechanics 1-day post-bleomycin predict persisting microatelectases throughout the respiratory cycle and increased alveolar strain during low positive end-expiratory pressure (PEEP) ventilation. As such, we hypothesize that mechanical ventilation in presence of microatelectases, which occur at low but not at higher PEEP, aggravates and unmasks ALI in the bleomycin injury model. Rats were randomized and challenged with bleomycin (B) or not (H = healthy). One day after bleomycin instillation the animals were ventilated for 3 h with PEEP 1 (PEEP1) or 5 cmH(2)O (PEEP5) and a tidal volume of 10 ml/kg bodyweight. Tissue elastance was repetitively measured after a recruitment maneuver to investigate the degree of distal airspace instability. The right lung was subjected to bronchoalveolar lavage (BAL), the left lung was fixed for design-based stereology at light- and electron microscopic level. Prior to mechanical ventilation, lung tissue elastance did not differ. During mechanical ventilation tissue elastance increased in bleomycin-injured lungs ventilated with PEEP = 1 cmH(2)O but remained stable in all other groups. Measurements at the conclusion of ventilation showed the largest time-dependent increase in tissue elastance after recruitment in B/PEEP1, indicating increased instability of distal airspaces. These lung mechanical findings correlated with BAL measurements including elevated BAL neutrophilic granulocytes as well as BAL protein and albumin in B/PEEP1. Moreover, the increased septal wall thickness and volume of peri-bronchiolar-vascular connective tissue in B/PEEP1 suggested aggravation of interstitial edema by ventilation in presence of microatelectases. At the electron microscopic level, the largest surface area of injured alveolar epithelial was observed in bleomycin-challenged lungs after PEEP = 1 cmH(2)O ventilation. After bleomycin treatment cellular markers of endoplasmic reticulum stress (p-Perk and p-EIF-2α) were positive within the septal wall and ventilation with PEEP = 1 cmH(2)O ventilation increased the surface area stained positively for p-EIF-2α. In conclusion, hidden microatelectases are linked with an increased pulmonary vulnerability for mechanical ventilation characterized by an aggravation of epithelial injury. |
format | Online Article Text |
id | pubmed-7530907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75309072020-10-17 Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury Albert, Karolin Krischer, Jeanne-Marie Pfaffenroth, Alexander Wilde, Sabrina Lopez-Rodriguez, Elena Braun, Armin Smith, Bradford J. Knudsen, Lars Front Physiol Physiology Mechanical ventilation of lungs suffering from microatelectases may trigger the development of acute lung injury (ALI). Direct lung injury by bleomycin results in surfactant dysfunction and microatelectases at day 1 while tissue elastance and oxygenation remain normal. Computational simulations of alveolar micromechanics 1-day post-bleomycin predict persisting microatelectases throughout the respiratory cycle and increased alveolar strain during low positive end-expiratory pressure (PEEP) ventilation. As such, we hypothesize that mechanical ventilation in presence of microatelectases, which occur at low but not at higher PEEP, aggravates and unmasks ALI in the bleomycin injury model. Rats were randomized and challenged with bleomycin (B) or not (H = healthy). One day after bleomycin instillation the animals were ventilated for 3 h with PEEP 1 (PEEP1) or 5 cmH(2)O (PEEP5) and a tidal volume of 10 ml/kg bodyweight. Tissue elastance was repetitively measured after a recruitment maneuver to investigate the degree of distal airspace instability. The right lung was subjected to bronchoalveolar lavage (BAL), the left lung was fixed for design-based stereology at light- and electron microscopic level. Prior to mechanical ventilation, lung tissue elastance did not differ. During mechanical ventilation tissue elastance increased in bleomycin-injured lungs ventilated with PEEP = 1 cmH(2)O but remained stable in all other groups. Measurements at the conclusion of ventilation showed the largest time-dependent increase in tissue elastance after recruitment in B/PEEP1, indicating increased instability of distal airspaces. These lung mechanical findings correlated with BAL measurements including elevated BAL neutrophilic granulocytes as well as BAL protein and albumin in B/PEEP1. Moreover, the increased septal wall thickness and volume of peri-bronchiolar-vascular connective tissue in B/PEEP1 suggested aggravation of interstitial edema by ventilation in presence of microatelectases. At the electron microscopic level, the largest surface area of injured alveolar epithelial was observed in bleomycin-challenged lungs after PEEP = 1 cmH(2)O ventilation. After bleomycin treatment cellular markers of endoplasmic reticulum stress (p-Perk and p-EIF-2α) were positive within the septal wall and ventilation with PEEP = 1 cmH(2)O ventilation increased the surface area stained positively for p-EIF-2α. In conclusion, hidden microatelectases are linked with an increased pulmonary vulnerability for mechanical ventilation characterized by an aggravation of epithelial injury. Frontiers Media S.A. 2020-09-18 /pmc/articles/PMC7530907/ /pubmed/33071807 http://dx.doi.org/10.3389/fphys.2020.530485 Text en Copyright © 2020 Albert, Krischer, Pfaffenroth, Wilde, Lopez-Rodriguez, Braun, Smith and Knudsen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Albert, Karolin Krischer, Jeanne-Marie Pfaffenroth, Alexander Wilde, Sabrina Lopez-Rodriguez, Elena Braun, Armin Smith, Bradford J. Knudsen, Lars Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury |
title | Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury |
title_full | Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury |
title_fullStr | Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury |
title_full_unstemmed | Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury |
title_short | Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury |
title_sort | hidden microatelectases increase vulnerability to ventilation-induced lung injury |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530907/ https://www.ncbi.nlm.nih.gov/pubmed/33071807 http://dx.doi.org/10.3389/fphys.2020.530485 |
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