While diffusion of gases across the lung is universally acknowledged to be an essential transport process, most models of pulmonary gas exchange assume that the gas phase component of diffusion does not influence measurements of pulmonary gas exchange. This project will employ trace amounts of various inert gases administered either intravenously or by the inhaled route to further investigate our preliminary findings that gases of high molecular weight are less efficiently eliminated from the lung in comparison with gases of lower molecular weight, finding we have attributed to gas phase diffusion limitation. Because the quantitative differences observed are small, data will first be obtained on the temperature and hemoglobin oxygen saturation corrections that are required for the Ostwald partition coefficients of each inert trace gas that will be used. A measurement of physiological dead space for an intravenously infused inert gas will be compared to an equivalent calculation made when the same gas is administered by the inhaled route to confirm the as yet undemonstrated assumption of the symmetry of exchange of gases. This experiment will be repeated utilizing an 80% Helium inhaled gas mixture to determine whether the larger (A-a) DO2 observed with He-O2 compared with room air will also be manifested by the inhaled inert trace gas. In an attempt to confirm that our observed molecular weight dependent impairment of inert gas elimination does represent gas phase diffusion limitation, we will repeat these studies with three trace inert gases using an He-O2 ambient gas, and also repeat the studies administering the trace inert gases by an inhaled route. Finally the corrections for temperature, hemoglobin oxygen saturation, and gas phase diffusion limitation will be applied to data obtained with the standard multiple inert gas elimination technique to determine whether our earlier report of active elimination of CO2 from the lung can be explained on the basis of our previous failure to account for these newly discovered factors. The proposed studies will provide quantitative data on the magnitude of this gas phase diffusive transport mechanism during normal gas exchange, will provide data for a number of current theoretical models of gas exchange incorporating both convection and diffusion that are under development and will provide a means of improving the precision of data obtained for use with the multiple inert gas elimination technique.
