Mechanisms of pulmonary edema clearance during acute hypoxemic respiratory failure: role of the Na,K-ATPase.
Pulmonary edema is the hallmark of acute respiratory distress syndrome. It occurs when the permeability of the alveolar-capillary barrier is increased, causing alveolar flooding and impaired gas exchange. The mechanisms of alveolar fluid resorption are different from those of alveolar edema formation. Alveolar fluid resorption into the vessels is brought about mainly by active transport of sodium ions (Na+) out of the alveolar spaces with water following the osmotic gradient. Na+ transport across the alveolar epithelium, and thus alveolar fluid resorption, is regulated by apical Na+ channels, the basolateral sodium potassium-adenosine triphosphatase (Na,K-ATPase), and possibly chloride channels. The Na,K-ATPase has been localized to the alveolar epithelium and the importance of its role in contributing to lung edema clearance has been demonstrated. In models of lung injury, several reports have shown that catecholamines such as isoproterenol and dopamine up-regulate Na+ channels and the Na,K-ATPase giving rise to increased alveolar fluid resorption. Although recombinant gene technology is not yet a therapeutic option for the treatment of pulmonary edema, several experimental studies have reported that overexpression of Na,K-ATPase genes causes increased fluid resorption during hyperoxic lung injury. There is significant evidence that fluid clearance is impaired in patients with lung injury. Therapeutic strategies aimed at increasing the ability of alveolar epithelium to resorb the edema should lead to benefits for patients with acute respiratory distress syndrome.
Dada
Laura A
LA
Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, 300 E. Superior, Tarry Building 14-707, Chicago, IL 60611, USA.
Sznajder
Jacob I
JI
D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000502:physiology*; D011654:Pulmonary Edema / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism / Q000502:physiology*
D000254:Sodium-Potassium-Exchanging ATPase