Tracheal osmolaity affects blood flow and the flux of a tracer, technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA), from tracheal lumen to venous blood in anesthetized sheep. Hyperosmolar liquids increase blood flow and slightly decrease 99mTc-DTPA flux, whereas hyposmolar liquids have no effect on blood flow and greatly increase 99mTc-DTPA flux. We have now investigated whether epithelial damage induced by exposure of the tracheal lumen to a detergent (0.2% Triton X-100) alters these effects. A tracheal artery was perfused, and tracheal venous blood was collected. The initial tracheal volume was 12.8 +/- 0.7 ml. Triton X-100 greatly increased the permeability coefficient for 99mTc-DTPA from -2.1 x 10(-7) to -240 x 10(-7) cm/s. Hyperosmolar Krebs-Henseleit solution (KH; 739 +/- 6 mosmol/kg) increased arterial (+14.3%) and venous (+21.5%) flows and decreased 99mTc-DTPA output by 51.7%. Water flux into the lumen (+0.3 +/- 0.1 ml) was not significant, and the osmolality decreased by 99 +/- 9 mosmol/kg. Hyposmolar KH (124 +/- 2 mosmol/kg) had no effect on arterial and venous flows (-1.3% for both), and the increase in 99mTc-DTPA output (+8.3%) was small and not significant. The volume decreased by 0.4 +/- 0.1 ml, and the osmolaity increased by 36 +/- 4 mosmol/kg. Thus epithelial damage greatly increases the baseline permeability of the tracheal wall to 99mTc-DTPA. It does not alter the qualitative effects of hypersomolar KH on blood flow and 99mTc-DTPA output but does reduce the effect of hyposmolar KH on 99mTc-DTPA output. The latter effect may be a consequence of the reduced net water movement in response to non-isosmolar solutions after epithelial damage.

Changes in the osmolality of airway surface liquid cause bronchoconstriction, mucus secretion, and ion transport, but little is known about the effects on the permeability of the trachea to drugs applied to the tracheal lumen. Using the anesthetized sheep, we have investigated the effects of hyperosmolar (725 +/- 11 mosmol/kg) and hyposmolar (128 +/- 5 mosmol/kg) Krebs-Henseleit (KH) solution in the tracheal lumen (mean volume 13.6 ml) on the uptake of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA), a low-molecular-mass hydrophilic tracer that is thought to cross the epithelium via paracellular pathways, and on blood flow. All changes in osmolality were made by altering the NaCl content. We perfused a tracheal artery and collected tracheal venous blood. Hyperosmolar KH increased water movement into the lumen (+2.0 ml) and solute flux out of the lumen. It increased arterial (+24.5%) and venous (+20.6%) flows and decreased 99mTc-DTPA concentration (-26.3%) and output (-12.0%) in venous blood. Hyposmolar KH caused water movement out of the lumen (-0.9 ml) and solute flux into the lumen. It had no effect on arterial (+0.6%) and venous (+5.5%) flows and greatly increased the concentration (+345%) and output (+375%) of 99mTc-DTPA in venous blood. The baseline permeability coefficient for 99mTc-DTPA (-9.1 x 10(-7) cm/s) was not affected by hyperosmolar KH (-8.7 x 10(-7) cm/s) but was increased by hyposmolar KH (-21.4 x 10(-7) cm/s). These results confirm that hyperosmolar liquid in the lumen increases blood flow and indicate that tracer uptake is affected by the bulk flow of water across the airway wall.

The tracheae of ferrets and rabbits were mounted in vitro in organ baths. While the tracheae were liquid filled, the permeability coefficient ( P) was determined, and then while the tracheae were air filled, the percent clearance for 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) was determined. The thickness of airway surface liquid (ASL) was estimated by three methods. 1) The initial concentration of 99mTc-DTPA and the total amount of 99mTc-DTPA (the sum of that entering the outside medium, that draining from the trachea, and that washed out at the end of 40 min) gave the initial volume of ASL and thus its thickness. Mean values were 45.7 micron for the ferret and 41.9 micron for the rabbit. 2) Estimates of ASL thickness at the end of the 40-min period, based on the final 99mTc-DTPA concentration and the amount in the washout, were 42.9 micron for ferret and 45.4 micron for rabbit. 3) The ratio of P to percent clearance gave mean ASL thickness values of 49.2 micron for the ferret and 40.3 micron for the rabbit. Thus three separate methods for determining ASL thickness give very similar results, with means in the range 40-49 micron. Administration of methacholine or atropine to ferret tracheae did not significantly change ASL thickness.