Ion composition of airway surface liquid of patients with cystic fibrosis as compared with normal and disease-control subjects.

To test whether a major contribution of airways epithelial ion transport to lung defense reflects the regulation of airway surface liquid (ASL) ionic composition, we measured ASL composition using the filter paper technique. On nasal surfaces, the Cl- concentration (approximately 125 meq/liter) was similar to plasma, but the Na+ concentration (approximately 110 meq/liter) was below plasma, and K+ concentration (approximately 30 meq/liter) above plasma. The resting ASL osmolarity [2(Na+ + K+); 277 meq/liter] approximated isotonicity. There were no detectable differences between cystic fibrosis (CF) and normal subjects. In the lower airways, the Na+ concentrations were 80-85 meq/liter, K+ levels approximately 15 meq/liter, and Cl- concentrations 75-80 meq/liter. Measurements of Na+ activity with Na(+)-selective electrodes and osmolality with freezing point depression yielded values consistent with the monovalent cation measurements. Like the nasal surfaces, no differences in cations were detected between CF, normal, or chronic bronchitis subjects. The tracheobronchial ASL hypotonicity was hypothesized to reflect collection-induced gland secretion, a speculation consistent with observations in which induction of nasal gland secretion produced hypotonic secretions. We conclude that there are no significant differences in ASL ion concentrations between CF, normal, and chronic bronchitis subjects and, because ASL ion concentrations exceed values consistent with defensin activity, the failure of CF lung defense may reflect predominantly factors other than salt-dependent defensins.

Measurement of cardiopulmonary function by rebreathing methodology in piglets.

The use of a multiple gas rebreathing method for the measurement of cardiopulmonary function in mechanically ventilated neonates was evaluated. The following indices of cardiopulmonary function were assessed in 20 piglets (mean weight, 2.3 kg): 1) pulmonary capillary blood flow (Qc), 2) diffusing capacity for carbon monoxide (DLCO), 3) lung gas volume (FRC), 4) oxygen consumption (VO2), and 5) volume of the pulmonary tissues and capillaries (VTPC), the latter an estimate of total lung water. During mechanical ventilation at zero end expiratory pressure, all rebreathing parameters correlated well with body weight. Additionally, a good correlation (r = 0.81, slope = 0.99) between VTPC and postmortem estimate of total lung water was observed. The effect of ventilation with positive end expiratory pressure (PEEP) was then studied in 10 piglets. On increasing PEEP from zero to 15 cm H2O, FRC significantly increased by 208%, Qc significantly decreased by 60%, and no changes in VTPC occurred. Seven piglets were then studied after induction of lung injury by oleic acid infusion. Compared with the pre-oleic acid infusion values, all the rebreathing variables decreased during ventilation without PEEP. Unlike the situation with the normal piglets, when PEEP was increased from zero to 10 cm H2O in the oleic acid-infused piglets, the values for FRC and VTPC significantly increased. Mean VTPC at 10 cm H2O was 20 +/- 2 ml/kg which correlated well (r = 0.93) with the postmortem total lung water value of 19 +/- 1 g/kg. Thus, multiple gas rebreathing methodology is applicable to studies using small animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Deposition, clearance, and effects of aerosolized amiloride in sheep airways.

Persistent Na+ absorption across a relatively Cl- impermeable epithelial barrier may contribute to the smaller water content of airway surface liquid (ASL) in cystic fibrosis. In this study, the feasibility and effectiveness of delivering an inhibitor of Na+ absorption, amiloride, by aerosol to the ASL of awake sheep was evaluated. Aerosolization of 6 X 10(-3) M amiloride, with [14C]amiloride, resulted in an estimated concentration of 7 X 10(-4) M in ASL. The transtracheal electric potential difference (PD), an index of the rate of Na+ absorption, was significantly inhibited (-29%) immediately after aerosolization of amiloride. The inhibition was short-lived and was correlated with rapid disappearance of the drug from ASL (half-time, 10.5 min between 0 and 30 min after aerosolization). Amiloride but not aerosol vehicle increased ASL volume significantly. The unidirectional flow of [14C]amiloride from the lumen to the submucosa across excised, short-circuited sheep airways exceeded flow from submucosa to lumen by a factor of at least 6. This finding suggests that amiloride is actively absorbed and is consistent with the rapid clearance from the airway surface and the short-lived effects of aerosolized amiloride in vivo. We conclude that sufficient concentrations of amiloride can be delivered to sheep airways by aerosol to inhibit PD and Na+ absorption for short periods.