Alveolar epithelial fluid clearance persists in the presence of moderate left atrial hypertension in sheep

Abstract

The effect of moderate left atrial (LA) hypertension on alveolar liquid clearance (ALC) was investigated in anesthetized, ventilated sheep, surgically prepared to measure lung lymph flow as well as hemodynamics. To simulate alveolar edema, 3-4 ml/kg of isosmolar 5% albumin in Ringer lactate were instilled into each lower lobe, and ALC was measured. After 4 h of LA hypertension (24 cmH2O), ALC was similar to that in control sheep (31 +/- 3% with LA hypertension vs. 34 +/- 10% with normal LA pressure). Because plasma epinephrine levels were moderately elevated in the presence of LA hypertension, ALC was then studied in the presence of LA hypertension following bilateral adrenalectomy. Without endogenous release of epinephrine, ALC was significantly reduced compared with normal LA pressure (20 +/- 7% compared with 34 +/- 10%, P < 0.05). Thus endogenous catecholamines caused a submaximal stimulation of ALC in the presence of LA hypertension. Exogenous administration of aerosolized beta2-agonist therapy with salmeterol increased ALC in the presence of normal LA pressure but had no stimulatory effect in the presence of moderate LA hypertension. Therefore, we tested the hypothesis that endogenous release of atrial natriuretic factor (ANF) may downregulate alveolar epithelial Na+ and fluid transport in the presence of LA hypertension. There was a modest twofold increase in plasma ANF levels after LA hypertension. Additional in vitro studies demonstrated that, in the presence of beta2-agonist stimulation, ANF decreased Na+ pump activity (Na+-K+-ATPase) in isolated rat alveolar epithelial type II cells. ANF may downregulate vectorial Na+ and fluid transport stimulated by endogenous or exogenous beta-adrenergic agonist stimulation in the presence of LA hypertension. In summary, ALC continues even in the presence of moderate LA hypertension. Aerosolized beta2-adrenergic agonist therapy significantly increased ALC, but only when LA pressure was normal.

Selected Contribution: Mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung

“…In the lung recipient, pulmonary edema due to reperfusion lung injury occurs in 15-35% of recipients and is a major cause of primary graft failure, morbidity, and mortality in the lung transplant population (39). ␤-Adrenergic agonists have been shown to enhance the resolution of pulmonary edema experimentally (6,8,33) and have a good safety profile in critically ill patients (10,19). Furthermore, the clinical utility of ␤-adrenergic agonists for one type of pulmonary edema has now been demonstrated: inhalation of the ␤-agonist salmeterol was recently shown to reduce the incidence of high-altitude pulmonary edema in those at risk (35).…”

β-Adrenoceptor stimulation of alveolar fluid clearance is increased in rats with heart failure

“…These include acute elevation of left atrial pressure (8,41), the creation of systemic left-to-right shunts (3), rapid electrical pacing of the heart (43-45), supracoronary aortic banding (24), as well as the coronary ligation technique used in this study. With respect to the lung's ability to clear alveolar fluid, acute increases in left atrial pressure have been shown to either depress baseline alveolar fluid clearance or inhibit the ability of ␤-adrenergic agonists to increase alveolar fluid clearance, whereas longer-term studies have shown either maintenance of or increased alveolar fluid clearance.…”

Salmeterol for the Prevention of High-Altitude Pulmonary Edema

“…4 Betaadrenergic agonists increase vectorial sodium transport in vitro, 5 enhance the clearance of alveolar fluid in the resected human lung 6 and in several species of animals, [7][8][9][10] and accelerate the resolution of pulmonary edema in animal models of lung injury. [11][12][13][14][15] However, the effects of beta-adrenergic agonists in the treatment of pulmonary edema in humans have not been assessed, and information demonstrating the importance of this vectorial sodium transport in the development of and recovery from pulmonary edema in humans is sparse and indirect. 16,17 In a double-blind, placebo-controlled study, we tested whether the prophylactic inhalation of the betaadrenergic agonist salmeterol at a dose shown to stimulate the clearance of alveolar fluid 18 decreases the incidence of pulmonary edema during exposure to high altitudes in subjects who are prone to high-altitude pulmonary edema.…”

“…2). [11][12][13][14][15] It is also possible that salmeterol, by improving alveolar ventilation and reducing alveolar hypoxia at high altitude, attenuates the hypoxiainduced impairment of alveolar absorption of sodium and fluid 27 in these subjects. Alternatively, salmeterol *Plus-minus values are means ±SD.…”