Pressure induced lung injury in a novel in vitro model of the alveolar interface: Protective effect of dexamethasone

Divya D. Nalayanda, William B. Fulton, Paul M. Colombani, Tza Huei Wang, Fizan Abdullah

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose The lungs of infants born with congenital diaphragmatic hernia suffer from immaturity as well as the short and long term consequences of ventilator-induced lung injury, including chronic lung disease. Antenatal and postnatal steroids are among current strategies promoted to treat premature lungs and limit long term morbidity. Although studied in whole-animal models, insight into ventilator-induced injury at the alveolar-capillary interface as well as the benefits of steroids, remains limited. The present study utilizes a multi-fluidic in vitro model of the alveolar-interface to analyze membrane disruption from compressive aerodynamic forces in dexamethasone-treated cultures. Methods Human alveolar epithelial cell lines, H441 and A549, were cultured in a custom-built chamber under constant aerodynamic shear followed by introduction of pressure stimuli with and without dexamethasone (0.1μM). On-chip bioelectrical measurements were noted to track changes to the cellular surface and live-dead assay to ascertain cellular viability. Results Pressure-exposed alveolar cultures demonstrated a significant drop in TEER that was less prominent with an underlying extracellular-matrix coating. Addition of dexamethasone resulted in increased alveolar layer integrity demonstrated by higher TEER values. Furthermore, dexamethasone-treated cells exhibited faster recovery, and the effects of pressure appeared to be mitigated in both cell types. Conclusion Using a novel in vitro model of the alveolus, we demonstrate a dose-response relationship between pressure application and loss of alveolar layer integrity. This effect appears to be alleviated by dexamethasone and matrix sub-coating.

Original languageEnglish (US)
Pages (from-to)61-65
Number of pages5
JournalJournal of pediatric surgery
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2014

Keywords

  • Air-interface culture
  • Alveolar cells
  • Dexamethasone
  • Pressure-induced injury

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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