To study the effect of increases in lung volume on solute uptake, we measured clearance of 99mTc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosol (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure [12 cmH2O continuous positive airway pressure (CPAP)] or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH2O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH2O; clearance and FRC were determined at CPAP of 12 cmH2O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method.

No abstract

We studied the effects of oleic acid (OA) on pulmonary clearance of three aerosolized radioactive solutes: 99mTc-diethylenetriamine pentaacetate (99mTc-DTPA), 67Ga-desferoxamine (67Ga-DFOM), and 111In-transferrin (111In-TF). Either 0.09 ml/kg OA or an equivalent volume of 0.9% NaCl (controls) was administered intravenously to 48 anesthetized, paralyzed dogs. Each animal received one aerosolized solute either 60 min after (protocol A) or 30 min before (protocol B) the infusion of OA or NaCl. In protocol A clearances of all three solutes were similar in OA and control animals. In contrast, in protocol B clearances of all three solutes increased significantly during OA infusion; during the next 60 min clearances of 99mTc-DTPA and 67Ga-DFOM returned to control values but 111In-TF remained increased. We conclude that 1) in OA-induced permeability edema pulmonary clearance of aerosolized solutes is increased when the aerosol is delivered 30 min before but not 60 min after injury, and 2) increased clearance persists only for large molecules, presumably because smaller molecules cross injured epithelium quickly and completely. These phenomena are best explained by a nonhomogeneous distribution of OA-induced injury.

To determine whether [14C]urea permeability-surface area product (PS) is a reliable indicator of changes in permeability in various injuries and its relationship to indicator-dilution and gravimetric lung water contents, we studied six groups of anesthetized, paralyzed, and mechanically ventilated dogs (5 animals each). The groups consisted of control dogs, those injured by intravenous alloxan, oleic acid, or glass beads, and those exposed to acute hypoxia or increased left atrial pressure from volume loading (Pla). Interanimal variation of PS was large (3.0-15.0 ml/s), but successive hourly values in individual animals were stable for 2 h in experimental groups and for 4 h in controls. The PS increased after alloxan, elevated Pla, and 2 h of hypoxia; PS decreased after oleic acid and microemboli. The gravimetric lung water increased after alloxan, oleic acid, and microemboli, and indicator-dilution lung water increased only after alloxan. We conclude 1) that intersubject variability requires normalization to enable detection of significant deviation from base line, and 2) that decreased PS after oleic acid and microvascular injury occurred because vascular obstruction, which decreased surface area, masked probable coexisting increases in capillary permeability.

To determine the value of subdividing diffusing capacity for carbon monoxide (DL) in diagnosing and monitoring the course of Pneumocystis carinii pneumonia (PCP), we measured DL, membrane diffusing capacity (DM), and pulmonary capillary blood volume (VC) in 20 control subjects, 20 patients with a low DL (less than 75% predicted) and newly diagnosed PCP, and 16 patients with a low DL in most of whom PCP had been suspected and excluded. Ten patients with PCP were restudied approximately 60 days after treatment. When clinically indicated, lung biopsies were obtained for histologic examination. Compared with mean values in control subjects (DL = 92%, DM = 101%, and VC = 35 ml/m2), all values were decreased (p less than 0.01) in patients with PCP (DL = 58%, DM = 33%, and VC = 26 ml/m2) and in those without PCP (DL = 61%, DM = 56%, and VC = 22 ml/m2). Values of DM were significantly less (p less than 0.05) in patients with, than in those without, PCP. Analysis of lung biopsies by light and electron microscopy showed overlapping morphologic abnormalities in the 2 groups of patients. In the 10 patients with PCP restudied after successful treatment, the mean DL increased from 60 to 80% (p less than 0.0005), the DM increased from 35 to 108% (p less than 0.006), and the VC did not change. These results suggest that in contrast to most disorders in which DL is decreased, PCP causes reversible alveolar-capillary block.