Estimation of thickness of airway surface liquid in ferret trachea in vitro

Abstract

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.

Both Ways at Once: Keeping Small Airways Clean

“…The continued patency and normal hygiene of these delicate tubes are assured not by air but by a layer of liquid and mucins that must constantly wash the luminal surfaces of all conductive airways via a "ciliated escalator" that constantly sweeps debris orally to be expelled in the pharynx (56,111). The depth (volume) of this layer of airway surface liquid (ASL) is critical, but reports of thickness vary from~10 m (106) in cultures of bronchial cells to Ն50 m in vivo in native trachea (29,54). Disturbances in the properties of either the liquid or the mucins are invitations for infection, inflammation, and pathology.…”

Oxidative Stress, the Paradigm of Ozone Toxicity in Plants and Animals

“…The lower, sol-phase of RTLF bathes the RTECs, whereas the upper, gel-phase entraps micro-organisms and large particles from the airstream. Furthermore, the thickness of the epithelial lining fluid varies along the respiratory tract: it is of 1-10 μm, in the upper airways, whereas, in the distal bronchoalveolar regions, the RTLF is only 0.2-0.5 μm thick (Quinton 1979;Duneclift et al 1997;Widdicombe 1997). In general, uric acid, a water-soluble oxidized purine base, is by far the most prevalent antioxidant in RTLF, in amounts that, in nasal cavity, approximate those of plasma (100-400 vs. 100-500 μM) (Peden et al 1990;Housley et al 1995, van der Vliet et al 1999.…”

Airway liquid: a barrier to drug diffusion?

“…Recent studies aggravate rather than resolve the dispute. Of sixteen studies on large airways in various species [13][14][15][18][19][20][21][22][23][24][25][26][27][28][29], values from 0-250 µm were obtained (table 2). There are no values for humans.…”