Steady-state ratios of the concentration in lymph to that in plasma were measured for "°I-serum albumin after 4 days of equilibration in unanesthetized dogs.

In anesthetized, ventilated dogs, clearance of 2 +/- 0.2 ml alveolar-instilled 1% isosmolar [125I]albumin ([125I]RISA) was separated into bulk airway displacement and transalveolar tissue permeation by the use of collimated external detectors and by sampling of blood and lymph. The detectors were positioned perpendicular to the plane of bronchial drainage, and collimator resolution was characterized by a 50% decrease in count rate for a 5-mm lateral (transbronchial) instillate shift. Detector signals demonstrated no airway shift in 10 dogs studied, the signal decay equaling [125I]RISA absorption determined by lung homogenates. The mean rate constants of [125I]RISA lung clearance and epithelial permeation were 4.08 X 10(-4)-min-1 and 5.48 X 10(-4)-min-1, respectively. The diffusional permeability coefficient of alveolar epithelium for albumin was 4.06 X 10(-9) CM-S-1. Absorbed [125I]RISA was separated into blood and lymph components by collecting lymph from the right lymphatic duct (RLD) and thoracic duct. Mean blood/lymph removal ratio was 6.3/1, and correlated with plasma/RLD lymph steady-state albumin concentration ratios in individual animals. Over a mean observation period of 5.4 h, an average of 12.3% [125I]RISA was cleared from the instilled region. The data suggest that this amount was cleared by permeation; there was little evidence of airway clearance.

No abstract

We tested the effects of alpha-naphthylthiourea (ANTU) on lung fluid balance and prostanoid concentrations in anesthetized sheep acutely prepared for collection of pulmonary lymph. Sheep were given 20, 50, 75, or 100 mg/kg ANTU or the vehicle dimethylsulfoxide (DMSO) intravenously. The first phase of the response consisted of transient increases in pulmonary artery pressure and plasma and lymph thromboxane B2 concentrations. Lymph flow increased with no change in the lymph-to-plasma protein concentration ratio (L/P). These changes occurred in sheep given DMSO alone or DMSO with ANTU; they were not dependent on the dose of ANTU given. Two to 4 h after drug administration, pulmonary artery pressure and thromboxane concentrations were normal or near normal. Lymph flow rate reached steady-state levels averaging 1.5 (DMSO alone) to 5.3 (100 mg/kg ANTU) times base line with L/P ratios unchanged from base line. ANTU/DMSO produces transient, severe pulmonary hypertension that may be prostaglandin mediated. The sustained response consists of increased flow rate of protein-rich lymph.

In experiments lasting 311 +/- 8 (SE) min, we studied the clearance of 125I-fibrinogen ([125I])RIF) from distal lung units of anesthetized, ventilated dogs. We instilled varying concentrations of isosmolar, citrated [125I]RIF ranging from 0.75 to 4 mg/ml into alveoli of individual dogs, and we monitored clearance by the use of external detectors and blood and lymph sampling. Approximately 9% [125I]RIF passed into proximal airways according to detector signal analysis. Excluding airway flow, whole lung clearance of [125I]RIF occurred by degradation to small molecules that rapidly became evenly distributed in body extracellular water. The degradation appeared to take place within the distal airway and not within the lung interstitium because 131I-fibrinogen, injected intravenously, was degraded less in passing from plasma to right duct lymph. The intra-alveolar kinetics of [125I]RIF had 1.5 reaction order with a specific rate of 1.27 X 10(-5) ml(3/2)-mg(-1/2)-min(-1). The data indicate that fibrinogen clearance from alveoli occurs by both transbronchial bulk flow and intraalveolar degradation.