Published ahead of print on August 28, 2003, doi:10.1164/rccm.200207-702OC
Am. J. Respir. Crit. Care Med., Volume 168, Number 12, December 2003, 1445-1448
A more recent version of this article appeared on December 15, 2003
Submitted on July 15, 2002
Accepted on August 24, 2003
Na,K-ATPase gene transfer increases liquid clearance during ventilation-induced lung injury
Yochai Adir1, Phillip Factor2, Vidas Dumasius3, Karen M Ridge1, and Jacob I Sznajder1*
1 Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL, USA,
2 Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL, USA; Evanston Northwestern Healthcare, Evanston, IL, USA,
3 Evanston Northwestern Healthcare, Evanston, IL, USA
* To whom correspondence should be addressed. E-mail: j-sznajder{at}northwestern.edu.
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 4x109 pfu of E1a-/E3- recombinant adenovirus containing either a rat  1 Na,K-ATPase subunit cDNA (ad1) or no cDNA (adnull) to rat lungs 7 days prior to ventilation with a VT of ~ 40 ml/kg (peak airway pressure <35 cm H2O) for 40 min. Lung liquid clearance and Na,K-ATPase activity and protein abundance was increased in HVT ad1-infected lungs as compared to sham and adnull infected HVT lungs. These results suggest that Na,K-ATPase subunit gene overexpression 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 utilizing a genetic approach improves active Na+ transport and thus liquid clearance in the setting of mild ventilation-induced lung injury.
Key words: Gene therapy, VILI, Na,K-ATPase
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