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

Author:

Wiegert Susanne123,Greco Francesco123,Baumann Philipp12ORCID,Wellmann Sven345,Grest Paula6,Hetzel Udo6,Cannizzaro Vincenzo123ORCID

Affiliation:

1. Department of Intensive Care Medicine and Neonatology, University Children’s Hospital Zurich, Zurich, Switzerland

2. Children’s Research Centre, University Children’s Hospital Zurich, Zurich, Switzerland

3. Zurich Centre for Integrative Human Physiology, Zurich, Switzerland

4. Department of Neonatology, University Children’s Hospital Basel, Basel, Switzerland

5. Department of Neonatology, University Children’s Hospital Regensburg, University of Regensburg, Regensburg, Germany

6. Vetsuisse Faculty, Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, University of Zurich, Zurich, Switzerland

Abstract

The poorly understood tolerance toward high tidal volume (VT) 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 VT 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. Rats (14 days old) were allocated to five groups: nonventilated controls, PEEP 5 cmH2O with VT of 8, 16, and 24 mL/kg, and PEEP 1 cmH2O with VT 24 mL/kg. Following 6 h 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. High VT (24 mL/kg) with PEEP of 5 cmH2O improved respiratory system mechanics and was not associated with lung injury, elevated surfactant protein expression, or surfactant phospholipid content. Extreme ventilation with VT 24 mL/kg and PEEP 1 cmH2O 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 (VT 24 mL/kg, PEEP 1 cmH2O) need further evaluation and might reflect accumulation of biophysically inactive small aggregates. In conclusion, our data confirm the resilience of infant rats toward high VT-induced lung injury and challenge the relevance of surfactant synthesis, storage, and secretion as protective factors.

Funder

Zurich Center for Integrative Human Physiology

EMDO Foundation

Donation by UBS AG in order of a client

Hartmann Mueller Foundation

Zurich Center of Human Physiology

Heartbay Foundation

Gottfried und Juli Bangerter-Rhyner-Foundation

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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