) Acute lung injury (ALI) is characterized by flooding of alveoli with fluid that creates a high degree of intrapulmonary shunt. Clearance of alveolar edema fluid is required for restoration of gas exchange. Transcellular epithelial sodium resorption by joint action of Na channel and Na, K-ATPase is critical in this process. Pharmacological stimulation of sodium and fluid resorption is possible in the normal lung, and the applicant previously demonstrated that terbutaline accelerates net alveolar sodium and fluid clearance in rat lungs injured by hyperoxia. Humans with ALI who resorb alveolar fluid have a better prognosis (Matthay 1990), but a mortality benefit of increasing alveolar fluid resorption has not been demonstrated. The goal of this project is to assess the effect of Na, K-ATPase over-expression on transepithelial sodium transport in vitro and on the resolution of lung injury in vivo. They will use viral vectors to transfer Na, K-ATPase genes to alveolar epithelial cells and test these hypotheses: (1) in vitro over-expression of Na, K-ATPase in epithelial cells increases Transcellular sodium and fluid transport; (2)in vivo over-expression of Na, K-ATPase increases alveolar fluid resorption in normal and in injured lungs; and (3) this effect benefits mortality in a lung injury model. This project is a logical extension of the applicant's previous physiologic studies of Na, K-ATPase upregulation and represents an excellent training vehicle, since he will acquire skills in molecular biology, gene transfer technology and electrophysiology.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003787-03
Application #
6138920
Study Section
Special Emphasis Panel (ZHL1-CSR-Y (O1))
Project Start
1998-01-15
Project End
2002-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
3
Fiscal Year
2000
Total Cost
$115,188
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455