Na,K-ATPase Gene Transfer Increases Liquid Clearance during Ventilation-induced Lung Injury

Yochai Adir, Phillip Factor, Vidas Dumasius, Karen M. Ridge, Jacob I. Sznajder*

*Corresponding author for this work

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Mechanical ventilation with high tidal volumes (HVT) downregulates alveolar Na,K-ATPase function and impairs lung liquid clearance. We hypothesized that overexpression of Na,K-ATPase in the alveolar epithelium could counterbalance these changes and increase clearance in a rat model of mild ventilation-induced lung injury. We used a surfactant-based system to deliver 4 x 109 plaque-forming units of E1a-/E3 - recombinant adenovirus containing either a rat β1, Na,K-ATPase subunit cDNA (adβ1 or no cDNA (adnull) to rat lungs 7 days before ventilation with a VT of approximately 40 ml/kg (peak airway pressure of less than 35 cm H2O) for 40 minutes. Lung liquid clearance and Na, K-ATPase activity and protein abundance were increased in HVT adβ1,-infected lungs as compared with sham and adnull-infected HVT lungs. These results suggest that Na,K-ATPase subunit gene over-expression in the alveolar epithelium increases Na,K-ATPase function and lung liquid clearance in a model of HVT. We provide here the first evidence that using a genetic approach improves active Na+ transport and thus liquid clearance in the setting of mild ventilation-induced lung injury.

Original languageEnglish (US)
Pages (from-to)1445-1448
Number of pages4
JournalAmerican journal of respiratory and critical care medicine
Volume168
Issue number12
DOIs
StatePublished - Dec 15 2003

Keywords

  • Gene therapy
  • Na,K-ATPase
  • Ventilation-induced lung injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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