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Published ahead of print on January 24, 2003, doi:10.1164/rccm.200204-312OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 10, May 2003, 1440-1450

A more recent version of this article appeared on May 15, 2003
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Submitted on April 12, 2002
Accepted on January 21, 2003

Alveolar liquid clearance and Na+ channel expression are decreased in transplanted canine lungs

Makoto Sugita1, Pasquale Ferraro2, Andre Dagenais3, Marie-Eve Clermont1, Pascal Barbry4, Rene P Michel5, and Yves Berthiaume3*

1 Centre de recherche, Centre hospitalier de l'Universite de Montreal, Hotel-Dieu du Chum, Montreal, Quebec, Canada, 2 Centre de recherche, Centre hospitalier de l'Universite de Montreal, Hotel-Dieu du Chum, Montreal, Quebec, Canada; Chirurgie, Universite de Montreal, Montreal, Quebec, Canada, 3 Centre de recherche, Centre hospitalier de l'Universite de Montreal, Hotel-Dieu du Chum, Montreal, Quebec, Canada; Medecine, Universite de Montreal, Montreal, Quebec, Canada, 4 Institut de pharmacologie cellulaire et moleculaire, CNRS, Universite Nice Sophia Antipolis, Sophia-Antipolis, France, 5 Pathology, McGill University, Montreal, Quebec, Canada

* To whom correspondence should be addressed. 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 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 alveolar liquid clearance, we also measured expression levels of the epithelial Na+channel (ENaC) and Na+-K+-ATPase. We found that alveolar liquid clearance was significantly lower in transplanted than in right native lungs ex vivo (p < 0.05), and that transplanted lungs did not respond to the {beta}-adrenergic agonist terbutaline. Our in vivo study confirmed the ex vivo results. Molecular analyses revealed that ENaC mRNA but not Na+-K+-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 clerance, epithelial sodium channel, Na-K-ATPase




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