Alveolar fluid reabsorption is increased in rats with compensated heart failure

Abstract

) is important in keeping the air spaces free of edema. This process is accomplished via active transport of Na ϩ across the alveolo-capillary barrier mostly by apical Na ϩ channels and basolateral Na ϩ -K ϩ -ATPases. Recently, we have reported that acute elevation of left atrial pressures is associated with decreased AFR in isolated rat lungs. However, the effect of chronic elevation of pulmonary capillary pressure, such as seen in patients with congestive heart failure (CHF), on AFR is unknown. CHF was induced by creating an aorto-caval fistula (ACF) in Sprague-Dawley male rats. Seven days after the placement of the fistula, AFR was studied in the isolated perfused rat lung model. AFR in control rats was 0.49 Ϯ 0.02 ml/h (all values are means Ϯ SE) and increased by ϳ40% (0.69 Ϯ 0.03 ml/h) in rats with chronic CHF (P Ͻ 0.001). The albumin flux from the pulmonary circulation into the air spaces did not increase in the experimental groups, indicating that lung permeability for large solutes was not increased. Na ϩ -K ϩ -ATPase activity and protein abundance at the plasma membrane of distal alveolar epithelial tissue were significantly increased in CHF rats compared with controls. These changes were associated with increased plasma norepinephrine levels in CHF rats compared with controls. We provide evidence that in a rat model of chronic compensated CHF, AFR is increased, possibly due to increased endogenous norepinephrine upregulating active sodium transport and protecting against alveolar flooding. edema; alveolar epithelium; Na ϩ -K ϩ -ATPase PULMONARY EDEMA DEVELOPS when fluid movement into the air space exceeds the ability of the lung to clear it (20, 37). Many in vivo and ex vivo models of normal and injured lungs have been used to determine the mechanisms by which excess air space fluid is cleared (8,13,26,29,34, 38). These studies have used models where fluid was either directly instilled into the lung or rapidly accumulated in the air space. However, there are no data regarding how the lung adapts to chronic imbalance of Starling forces as occurs in congestive heart failure (CHF). Tandon and Kasturi (40) reported that in patients with mitral stenosis, the pulmonary tissue remodels in response to chronically elevated left atrial pressure; the arterioles were muscularized with pronounced intimal proliferation. Other changes included medial hypertrophy in the veins and occasional muscularization and dilatation of the lymphatics. Patients with CHF have chronically elevated pulmonary capillary pressures, yet they develop frank pulmonary edema only occasionally and intermittently. These clinical features thus suggest that the lung must have mechanisms to compensate for chronic elevation of pulmonary hydrostatic pressures leading to lung edema. These mechanisms have not been previously defined.Recently, several studies have shown that exposure to acute elevation in left atrial pressures impairs alveolar fluid reabsorption (AFR) in rat lungs; however, exogenous administration of catecholamines and overexpressi...

Lung fluid clearance in chronic heart failure patients

“…This result supports previous animal investigations in isolated perfused lungs from volume overload CHF [12,13], as well as the trend observed in a decompensated patient population [14], in which there is an increase in alveolar fluid clearance, but is inconsistent with our previous findings in the isolated nonperfused rat lung [8].…”

“…It has been suggested that increased rate of alveolar fluid clearance in CHF may be due to an increase in the absolute expression and activation of vectorial fluid channels on both endothelial and epithelial cells, controlled through a nitric oxide negative feedback mechanism [12,13]. This mechanism, which allows for an increase in fluid flux capacity of the lung in CHF, provides a possible explanation for our previous finding of…”

“…However, in order to explain our finding of decreased alveolar clearance in the non-perfused CHF lung, this mechanism would necessitate a sequential activation whereby the endothelium is activated prior to activation of these channels on the epithelium. In addition, changes in the expression of these channels have not been consistently observed, including in our animal study [8,12].…”

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

“…With respect to the former, Campbell and colleagues (8) found that instilled ␤ 2 -agonists failed to stimulate alveolar fluid clearance in sheep in which left atrial pressure had been increased for 4 h. Consistent results were observed in ex vivo isolated, perfused rat lungs (41), where lung fluid absorption was decreased following an hour elevation of left atrial pressure. In contrast, over a longer time frame of 7 days, Azzam and colleagues (3) observed that baseline alveolar fluid clearance was increased in rats with compensated heart failure produced by an aorto-caval fistula. These authors suggested that this response was mediated by an increased endogenous plasma norepinephrine upregulation of active Na transport.…”

Patterns of alveolar fluid clearance in heart failure

“…1B and C respectively). We suggested that this upregulation of Na + transport is enhanced in order to keep the alveolar spaces free of edema in experimental chronic CHF [41].…”