The most important consequence of lung disease is hypoxemia. This research program continues its commitment ot understanding the causes and effects of hypoxemia in health and disease. We propose a series of projects, most of which have existed in and evolved from the present grant cycle, that have the overall objective of understanding how structural elements of the O2 transport chain determine and regulate O2 transport. The program is interdisciplinary and interdepartmental, =with investigators from the UCSD Departments of medicine, Bioengineering and Mathematics, and from University of California, Davis. As previously, we integrate theoretical considerations, cellular and molecular approaches, organ level studies, whole animal work and measurements in intact man. Studies encompass normal tissues, models of disease, and several human disease states. Project 1 (Wagner) deals with mechanisms of maximal O2 transport limitation; Project 2 (Mathieu-Costello) relates skeletal muscle structure to its energetic function; Project 3 (Poole) examines structure-function relations and O2 transport in the diaphragm in heath and disease; Project 4 (Powell) continues to define mechanisms of chemoreceptor response to hypoxia at the system and organ level while Project 5 (Hempleman) addresses the same issues at a cellular and subcellular level. The five projects are supported by the same cores as in the present cycle except that the electronics core has been amalgamated with the computing core to reduce costs, resulting in three cores; morphology/ morphometry, electronics/computing and administrative. All Projects except 3 and 5 are continuations of existing projects, and are led by the same investigators as in the current cycle; Projects 3 and 5 are proposed by individuals who already feature prominently in the present grant cycle as coinvestigators and who have now matured to project leadership within our research group.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL017731-23
Application #
2415526
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
1975-03-01
Project End
2000-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
23
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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
Poole, David C; Copp, Steven W; Ferguson, Scott K et al. (2013) Skeletal muscle capillary function: contemporary observations and novel hypotheses. Exp Physiol 98:1645-58
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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