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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Chang, Hung; Lai-Fook, Stephen J; Domino, Karen B et al. (2006) Redistribution of blood flow and lung volume between lungs in lateral decubitus postures during unilateral atelectasis and PEEP. Chin J Physiol 49:83-95
Chang, Hung; Lai-Fook, Stephen J; Domino, Karen B et al. (2006) Ventilation and perfusion distribution during altered PEEP in the left lung in the left lateral decubitus posture with unchanged tidal volume in dogs. Chin J Physiol 49:74-82
Robertson, H Thomas; Kreck, Thomas C; Krueger, Melissa A (2005) The spatial and temporal heterogeneity of regional ventilation: comparison of measurements by two high-resolution methods. Respir Physiol Neurobiol 148:85-95
Hubler, Matthias; Souders, Jennifer E; Shade, Erin D et al. (2002) Effects of perfluorohexane vapor on relative blood flow distribution in an animal model of surfactant-depleted lung injury. Crit Care Med 30:422-7
Chang, Hung; Lai-Fook, Stephen J; Domino, Karen B et al. (2002) Spatial distribution of ventilation and perfusion in anesthetized dogs in lateral postures. J Appl Physiol 92:745-62
Kreck, T C; Shade, E D; Lamm, W J et al. (2001) Isocapnic hyperventilation increases carbon monoxide elimination and oxygen delivery. Am J Respir Crit Care Med 163:458-62
Kreck, T C; Krueger, M A; Altemeier, W A et al. (2001) Determination of regional ventilation and perfusion in the lung using xenon and computed tomography. J Appl Physiol 91:1741-9
Lim, C M; Domino, K B; Glenny, R W et al. (2001) Effect of increasing perfluorocarbon dose on VA/Q distribution during partial liquid ventilation in acute lung injury. Anesthesiology 94:637-42
Hubler, M; Souders, J E; Shade, E D et al. (2001) Effects of vaporized perfluorocarbon on pulmonary blood flow and ventilation/perfusion distribution in a model of acute respiratory distress syndrome. Anesthesiology 95:1414-21
Brogan, T V; Hedges, R G; McKinney, S et al. (2000) Pulmonary NO synthase inhibition and inspired CO2: effects on V'/Q' and pulmonary blood flow distribution. Eur Respir J 16:288-95

Showing the most recent 10 out of 55 publications