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Impact of high tidal volume ventilation on surfactant metabolism and lung injury in infant rats


Wiegert, Susanne; Greco, Francesco; Baumann, Philipp; Wellmann, Sven; Grest, Paula; Hetzel, Udo; Cannizzaro, Vincenzo (2020). Impact of high tidal volume ventilation on surfactant metabolism and lung injury in infant rats. American Journal of Physiology. Lung Cellular and Molecular Physiology, 319(3):L562-L575.

Abstract

The poorly understood tolerance towards high tidal volume (V<jats:sub>T</jats:sub>) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high V<jats:sub>T</jats:sub> with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion leading to improved lung function and whether extreme mechanical ventilation affects intracellular lamellar body formation and exocytosis. Fourteen days old rats were allocated to five groups: non-ventilated controls, PEEP 5 cmH<jats:sub>2</jats:sub>O with V<jats:sub>T</jats:sub> of 8, 16, and 24 mL/kg, respectively, and PEEP 1 cmH<jats:sub>2</jats:sub>O with V<jats:sub>T</jats:sub> 24 mL/kg. Following 6 hours of ventilation, lung function, surfactant proteins and phospholipids, and lamellar bodies were assessed by forced oscillation technique, quantitative real-time polymerase chain reaction, mass spectrometry, immunohistochemistry, and transmission electron microscopy, respectively. High V<jats:sub>T</jats:sub> (24 mL/kg) with PEEP of 5 cmH<jats:sub>2</jats:sub>O improved respiratory system mechanics and was not associated with lung injury, elevated surfactant protein expression, or surfactant phospholipid content. Extreme ventilation with V<jats:sub>T</jats:sub> 24 mL/kg and PEEP 1 cmH<jats:sub>2</jats:sub>O produced a mild inflammatory response and correlated with higher surfactant phospholipid concentrations in bronchoalveolar lavage fluid without affecting lamellar body count and morphology. Elevated phospholipid concentrations in the potentially most injurious strategy (V<jats:sub>T</jats:sub> 24 mL/kg, PEEP 1 cmH<jats:sub>2</jats:sub>O) need further evaluation and might reflect accumulation of biophysically inactive small aggregates. In conclusion, our data confirm the resilience of infant rats towards high V<jats:sub>T</jats:sub>-induced lung injury and challenge the relevance of surfactant synthesis, storage, and secretion as protective factors.

Abstract

The poorly understood tolerance towards high tidal volume (V<jats:sub>T</jats:sub>) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high V<jats:sub>T</jats:sub> with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion leading to improved lung function and whether extreme mechanical ventilation affects intracellular lamellar body formation and exocytosis. Fourteen days old rats were allocated to five groups: non-ventilated controls, PEEP 5 cmH<jats:sub>2</jats:sub>O with V<jats:sub>T</jats:sub> of 8, 16, and 24 mL/kg, respectively, and PEEP 1 cmH<jats:sub>2</jats:sub>O with V<jats:sub>T</jats:sub> 24 mL/kg. Following 6 hours of ventilation, lung function, surfactant proteins and phospholipids, and lamellar bodies were assessed by forced oscillation technique, quantitative real-time polymerase chain reaction, mass spectrometry, immunohistochemistry, and transmission electron microscopy, respectively. High V<jats:sub>T</jats:sub> (24 mL/kg) with PEEP of 5 cmH<jats:sub>2</jats:sub>O improved respiratory system mechanics and was not associated with lung injury, elevated surfactant protein expression, or surfactant phospholipid content. Extreme ventilation with V<jats:sub>T</jats:sub> 24 mL/kg and PEEP 1 cmH<jats:sub>2</jats:sub>O produced a mild inflammatory response and correlated with higher surfactant phospholipid concentrations in bronchoalveolar lavage fluid without affecting lamellar body count and morphology. Elevated phospholipid concentrations in the potentially most injurious strategy (V<jats:sub>T</jats:sub> 24 mL/kg, PEEP 1 cmH<jats:sub>2</jats:sub>O) need further evaluation and might reflect accumulation of biophysically inactive small aggregates. In conclusion, our data confirm the resilience of infant rats towards high V<jats:sub>T</jats:sub>-induced lung injury and challenge the relevance of surfactant synthesis, storage, and secretion as protective factors.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
05 Vetsuisse Faculty > Institute of Veterinary Pathology
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:Physiology (medical), Cell Biology, Physiology, Pulmonary and Respiratory Medicine
Language:English
Date:1 September 2020
Deposited On:13 Aug 2020 14:01
Last Modified:24 Jun 2021 00:00
Publisher:American Physiological Society
ISSN:1040-0605
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1152/ajplung.00043.2020
PubMed ID:32579393
Project Information:
  • : FunderFP7
  • : Grant ID201690
  • : Project TitleFAST-XDR-DETECT - Development of a two-approach plate system for the fast and simultaneous detection of MDR and XDR M. tuberculosis
  • : FunderSNSF
  • : Grant ID1000-000001
  • : Project TitleSchlussband (Bd. VI) der Jacob Burckhardt-Biographie
  • : FunderSNSF
  • : Grant ID1000-000001
  • : Project TitleSchlussband (Bd. VI) der Jacob Burckhardt-Biographie
  • : FunderSNSF
  • : Grant ID1000-000001
  • : Project TitleSchlussband (Bd. VI) der Jacob Burckhardt-Biographie
  • : FunderFP7
  • : Grant ID212966
  • : Project TitleRELIAWIND - Reliability focused research on optimizing Wind Energy systems design, operation and maintenance: Tools, proof of concepts, guidelines & methodologies for a new generation.
  • : FunderSNSF
  • : Grant ID1000-000001
  • : Project TitleSchlussband (Bd. VI) der Jacob Burckhardt-Biographie
  • : FunderSNSF
  • : Grant ID1000-000001
  • : Project TitleSchlussband (Bd. VI) der Jacob Burckhardt-Biographie

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