This is an interdisciplinary, interdepartmental Program Project on the physiological basis of pulmonary disease. Research is principally directed toward the mechanisms of ventilation and bloodflow, and studies of gas exchange. Progress has been made on the morphology of muscle capillaries during muscle contraction and extension. In addition, the capillary supply of bird flight muscle has been studied in an effort to improve our understanding of oxygen unloading in tissues that have a high oxygen demand. Both these studies will be extended during the next year of support. Further work is continuing on the multiple inert gas elimination technique for determining distributions of ventilation-perfusion ratios. These studies involving moment analysis will be further extended. An extensive program on oxygen transport during hypothermia has made considerable progress but additional work is planned in the areas of anemic hypoxia and stagnant hypoxia during hypothermia. Work is proceeding on gas exchange in alligator lungs where the effects of stratification are likely to be important. Further experiments on molecular weight dependence of gas exchange in these lungs which form a useful model of some types of human disease are planned. Studies have been carried out on gas exchange in normal man during hypoxic exercise to determine the extent of diffusion impairment, and further work in this area is planned for the coming year. Studies of intermediary metabolism of Harbor seals during rest and exercise have been completed but additional work on energetics in marine mammals, especially using noninvasive procedures, will be carried out.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Research Review Committee A (HLBA)
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Richardson, Russell S; Wary, Claire; Wray, D Walter et al. (2015) MRS Evidence of Adequate O? Supply in Human Skeletal Muscle at the Onset of Exercise. Med Sci Sports Exerc 47:2299-307
Esposito, F; Wagner, P D; Richardson, R S (2015) Incremental large and small muscle mass exercise in patients with heart failure: evidence of preserved peripheral haemodynamics and metabolism. Acta Physiol (Oxf) 213:688-99
Olfert, I Mark; Malek, Moh H; Eagan, Tomas M L et al. (2014) Inflammatory cytokine response to exercise in alpha-1-antitrypsin deficient COPD patients 'on' or 'off' augmentation therapy. BMC Pulm Med 14:106
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Koga, S; Wüst, R C I; Walsh, B et al. (2013) Increasing temperature speeds intracellular PO2 kinetics during contractions in single Xenopus skeletal muscle fibers. Am J Physiol Regul Integr Comp Physiol 304:R59-66
Breen, Ellen C; Malloy, Jaret L; Tang, Kechun et al. (2013) Impaired pulmonary defense against Pseudomonas aeruginosa in VEGF gene inactivated mouse lung. J Cell Physiol 228:371-9
Tang, Kechun; Murano, George; Wagner, Harrieth et al. (2013) Impaired exercise capacity and skeletal muscle function in a mouse model of pulmonary inflammation. J Appl Physiol 114:1340-50
Wray, D Walter; Nishiyama, Steven K; Donato, Anthony J et al. (2011) The paradox of oxidative stress and exercise with advancing age. Exerc Sport Sci Rev 39:68-76
Esposito, Fabio; Mathieu-Costello, Odile; Entin, Pauline L et al. (2010) The skeletal muscle VEGF mRNA response to acute exercise in patients with chronic heart failure. Growth Factors 28:139-47
Wray, D Walter; Nishiyama, Steve K; Donato, Anthony J et al. (2010) Human vascular aging: limb-specific lessons. Exerc Sport Sci Rev 38:177-85

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