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Published ahead of print on January 24, 2003, doi:10.1164/rccm.200204-312OC
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American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 1440-1450, (2003)
© 2003 American Thoracic Society

Alveolar Liquid Clearance and Sodium Channel Expression Are Decreased in Transplanted Canine Lungs

Makoto Sugita, Pasquale Ferraro, André Dagenais, Marie-Eve Clermont, Pascal Barbry, René P. Michel and Yves Berthiaume

Centre de Recherche, Centre hospitalier de l'Université de Montréal, Hôtel-Dieu; Départements de médecine et de chirurgie, Université de Montréal; Department of Pathology, McGill University, Montréal, Québec, Canada; CNRS/UNSA UMR 6097, IPMC, F-06560 Sophia-Antipolis, France

Correspondence and requests for reprints should be addressed to Dr. Yves Berthiaume, M.D., M.Sc., Centre de recherche, Hôtel-Dieu du CHUM, 3850 St-Urbain, Montréal, Québec H2W 1T7, Canada. E-mail: yves.berthiaume{at}umontreal.ca

To determine the impact of transplantation-associated injury on the clearance mechanisms of pulmonary edema, we created a canine single lung transplant model. After 3 hours of preservation and 4 hours of reperfusion, right native lungs and left transplanted lungs were used to measure alveolar liquid clearance (ALC) in ex vivo liquid-filled lung preparations. We also examined the role of the pulmonary circulation in edema clearance in in vivo liquid-filled lungs between 4 and 8 hours of reperfusion. To study molecular modifications in ALC, we also measured expression levels of the epithelial sodium channel (ENaC) and sodium–potassium–adenosine triphosphatase (ATPase). We found that ALC was significantly lower in transplanted than in right native lungs ex vivo (p < 0.05) and that transplanted lungs did not respond to the ß-adrenergic agonist terbutaline. Our in vivo study confirmed the ex vivo results. Molecular analyses revealed that ENaC messenger RNA but not sodium–potassium–ATPase was significantly decreased in transplanted lungs (p < 0.01). Furthermore, there was a significant decrease in ENaC protein expression. Therefore, we conclude that the current investigation indicates that the lung injury caused by lung preservation and transplantation significantly reduces the edema clearance ability of transplanted lungs.

Key Words: lung transplantation • ischemia–reperfusion injury • alveolar liquid clearance • epithelial sodium channel • sodium–potassium–adenosine triphosphatase




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