This proposal will study the independent influences of changes in lobar perfusion, ventilation, and alveolar gas composition on the matching of ventilation to perfusion in normal lungs and in diseased lungs characterized by permeability edema utilizing the analysis of exchange of a spectrum of trace inert gases. The first general aim will be to investigate the relationship of increases in pulmonary blood flow and gas exchange heterogeneity. To study this aim, a dog model in which a left upper lobectomy is performed, the left lower lobe (LLL) is independently ventilated, and a LLL pulmonary venous catheter is inserted, will be used. Blood flow to the LLL will be increased and decreased by vascular occluders, while maintaining constant ventilation and end-tidal carbon dioxide tension. Measurements in animals with normal lungs and oleic acid-lung injury will be compared. Measurements at different pulmonary artery pressures will also be compared in dogs with normal lungs. The second general aim will be to investigate the relationship of increases in minute ventilation and gas exchange heterogeneity in dogs with normal and oleic acid-injured lungs. Using a dog partially isolated lobe preparation, minute ventilation will be increased while maintaining constant lobe perfusion and end-tidal carbon dioxide tension. Measurements obtained at different tidal volumes, respiratory rates, and lung volumes will be compared. The final general aim will be to investigate the relationship of alveolar oxygen and carbon dioxide tensions with gas exchange heterogeneity. Using a dog model with a LLL pulmonary venous catheter, inspired oxygen tension to the LLL will be varied while maintaining constant perfusion and ventilation. Measurements in normal and oleic acid-injured lungs will be compared. Gas exchange measurements will also be compared at different levels of end-tidal carbon dioxide tension in dogs with normal and oleic acid-injured lungs. The NHLBl Clinical Investigator Award will provide the opportunity for the candidate to develop into an independent biomedical research investigator. The candidate graduated from the University of Michigan Medical School and received clinical training in anesthesia and research training in the physiology of atelectasis and regional hypoxic pulmonary vasoconstriction at the University of Pennsylvania. The candidate is currently an assistant professor in the Department of Anesthesiology at the University of Washington. The university contains a large number of investigators and resources in the field of pulmonary physiology including the area of gas exchange.
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