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

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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 β2-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 β2-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 β-adrenergic agonist stimulation in the presence of LA hypertension. In summary, ALC continues even in the presence of moderate LA hypertension. Aerosolized β2-adrenergic agonist therapy significantly increased ALC, but only when LA pressure was normal.