Acid-base disturbances, such as metabolic or respiratory alkalosis, are relatively common in critically ill patients. We examined the effects of alkalosis (hypocapnic or metabolic alkalosis) on alveolar fluid reabsorption in the isolated and continuously perfused rat lung model. We found that alveolar fluid reabsorption after 1 hour was impaired by low levels of CO 2 partial pressure (PCO 2 ; 10 and 20 mm Hg) independent of pH levels (7.7 or 7.4). In addition, PCO 2 higher than 30 mm Hg or metabolic alkalosis did not have an effect on this process. The hypocapnia-mediated decrease of alveolar fluid reabsorption was associated with decreased Na,K-ATPase activity and protein abundance at the basolateral membranes of distal airspaces. The effect of low PCO 2 on alveolar fluid reabsorption was reversible because clearance normalized after correcting the PCO 2 back to normal levels. These data suggest that hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption. Conceivably, correction of hypocapnic alkalosis in critically ill patients may contribute to the normalization of lung ability to clear edema.Keywords: alveolar epithelial cells; hypocapnic alkalosis; ion transport; Na,K-ATPase; pulmonary edemaThe resolution of pulmonary edema is the result of active sodium transport across the alveolar epithelium (1-5). Sodium enters the alveolar epithelial cells via apically located sodium channels, and it is extruded via basolaterally located sodium pumps (Na, K-ATPases), which causes water to be reabsorbed from the alveolar space (4, 6-10). In experimental models, it has been reported that alveolar fluid reabsorption (AFR) is decreased during acute hyperoxia (11), hypoxia (12), ventilator-associated lung injury (13), increased left atrial pressures (14), infection (15), and scorpion envenomation (16). In some of these models of lung injury, the impairment in AFR has been associated with decreased Na,K-ATPase activity and protein abundance at the basolateral membrane of alveolar epithelial cells (13,(16)(17)(18).Acid-base disturbances and particularly hypocapnia can be observed during hyperventilation because it may occur during air travel, hiking at high altitudes, early asthma attack, diabetic ketoacidosis, or systemic inflammatory response syndrome (19)(20)(21)(22). The effect of hypocapnic alkalosis on alveolar fluid reabsorption as an index of alveolar epithelial function has not been eluci- dated. However, it has been reported that when AFR is impaired in patients with lung dysfunction, it is associated with worst outcomes (23).The present study examined the effects of hypocapnic alkalosis by changing the levels of CO 2 in the pulmonary circulation of the isolated, perfused, fluid-filled rat lung model. In parallel experiments, we examined the effects of CO 2 partial pressure (Pco 2 ) changes on Na,K-ATPase activity and protein abundance at the plasma membranes of distal airspaces.
METHODSPathogen-free male Sprague-Dawley rats weighing 320 to 350 g were purchased from Harlan Sprague Dawley (Indiana...