KINETICS OF UREA EXCHANGE IN AIR-FILLED AND FLUID-FILLED RAT LUNGS

Urea has been used as an indicator for estimating 1) the dilution of epithelial lining fluid (ELF) that occurs during bronchoalveolar lavage (BAL) and 2) the permeability-surface area product (PS) of the pulmonary endothelium to this solute. Because relatively little is known about how urea equilibrates with fluid in the lung tissues and airspaces, we have undertaken a study of the kinetics of movement from the vasculature into the tissues of isolated, perfused rat lungs. Although instillation of 5 ml of 154 mM saline into the airspaces of this preparation increased the calculated extravascular volume of (HOH)-H-3 from 0.64 +/- 0.23 to 2.10 +/- 0.58 ml (SE, n = 6) during a single transit through the pulmonary circulation, it did not have a detectable effect on the distribution of [C-14]urea in the lung tissues. However, leakage of [C-14]urea into saline within the airspaces was detected during constant infusions: concentrations in the airspace fluid reached 1.1 +/- 0.2% of those in the perfusate by 90 s and 1.90 +/- 0.2% at 120 s, levels that would significantly reduce estimates of the dilution of ELF by BAL. In contrast, concentrations of Tc-99m-diethylenetriaminepentaacetic acetic acid (DTPA) in the airspaces remained <0.2% of those in the perfusate, suggesting that Tc-99m-DTPA may be a superior indicator for estimating dilution of ELF by BAL. By 2 min, [C-14]urea had equilibrated with 1.28 +/- 0.17 ml of lung tissue suggesting that 1) cellular distribution as well as transcapillary diffusion may determine the extraction of [C-14]urea, complicating interpretation of PS measurements made with this indicator and 2) the pulmonary epithelium slows distribution of urea into the airspaces. No evidence was found for urea transporters in the pulmonary vasculature comparable to those found in some other tissues.