This proposal will investigate three inter-related aspects of respiratory gas exchange utilizing the analysis of exchange of a spectrum of trace inert gases. The first general aim will be to identify the mechanism responsible for the impaired elimination of higher molecular weight (MW) gases from the lung which we have documented. Three hypotheses will be considered and tested using a partially isolated dog left lower lobe. 1) The MW related differences in gas exchange arise because of diffusive-convective interactions within the terminal airways. Measurements before and after augmentation of convective gas movement will be compared. 2) The MW related differences are due to a gas phase diffusion resistance in the alveoli. Measurements will be compared at different alveolar volumes. 3) The MW related differences arise because of a heterogeneity of pulmonary transit time preventing full alveolar-capillary diffusion equilibration in some units. Measurements at different pulmonary vascular flow rates and with continuous or pulsatile flow regimens will be compared. The next general aim will investigate the importance of mixing mechanisms in the lung induced by the beating heart. Using the dog isolated lobe preparations we will be able to separately analyze the airway stirring effects of cardiac pulsations from the perfusion changes caused by pulsatile movement of blood in the vasculature. The importance of collateral ventilation in this mixing effect will be studied by performing the same measurements on young pigs with poor collateral ventilation. The final general aim will be to investigate the relationship between tracheal blood flow and tracheal gas exchange in the dog, and skin blood flow and skin gas exchange in the frog. Both of the latter systems may show significant epithelial diffusion resistance and have a wide range of physiological flow rates. Epithelial flow rates will be monitored with a laser-Doppler flow probe during measurements of gas exchange. Gas exchange through these epithelial tissues will be influenced by the interaction between epithelial diffusion barriers and tissue perfusion.