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COPD: oxygen transport and metabolism in skeletal muscle

Institution: University of California, San Diego
Investigator(s): Luke Haseler, Ph.D.
Award Cycle: 2001 (Cycle 10) Grant #: 10KT-0335 Award: $224,500
Subject Area: Pulmonary Disease
Award Type: New Investigator Awards
Abstracts

Initial Award Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction. COPD predominantly encompasses chronic bronchitis and emphysema, and affects up to 15 million people in the United States. While the mortality rates associated with other chronic illnesses such as cardiovascular disease and stroke have declined over the last 20 years, the mortality rate for COPD rose nearly 33% from 1979 to 1991. The major factor associated with the development of COPD is cigarette smoking. A major impact on the quality of life of patients with COPD is a reduced tolerance for exercise. In this case exercise refers to the ability to perform everyday tasks. While it is intuitive to think that damage to the lungs is responsible for exercise intolerance, recent evidence suggests that the skeletal muscles of COPD patients may also be impaired. However, the prevalence of this skeletal muscle dysfunction and the mechanisms responsible for it are not well understood. By the nature of the disease the skeletal muscles of COPD patients become deconditioned, thus a focus of this research will be examining the contributions of skeletal muscle disuse to the exercise intolerance associated with COPD.

Crucial to examining the question of skeletal muscle disuse versus dysfunction in COPD is an understanding of the relationship between blood flow to the exercising muscle and the ability of the muscle to use the oxygen that is carried by the blood. We will conduct a clinical study in which COPD patients and healthy individuals will exercise their calf muscles by pushing on a pedal. This type of exercise only involves a small muscle mass thus removing the limitation to exercise caused by airflow obstruction in COPD. While the subjects are performing the exercise, state-of-the-art techniques will be used to measure blood flow and metabolism in the exercising muscle. Doppler flowmetry will assess the blood flow to the muscle during exercise and this will determine if sufficient oxygen is being delivered to the muscles. Magnetic resonance spectroscopy and magnetic resonance imaging will measure the metabolism of the muscles and the ability of the muscles to use oxygen during exercise. This combination of techniques will assess the contributions of the peripheral factors of blood flow and muscle metabolism to the reduced exercise tolerance of COPD patients.

The results of this research may allow guidance and evaluations of interventions designed to improve exercise tolerance in COPD patients. Long tern goals include the application of these techniques to assess the effects of interventions such as exercise training, and lung transplantation on skeletal muscle oxygen delivery.
Publications

Local perfusion and metabolic demand during exercise: a non-invasive MRI method of assessment.
Periodical: Journal of Applied Physiology Index Medicus:
Authors: Richardson RS, Haseler LJ, Nygren AT, Bluml S, and Frank LR ART
Yr: 2001 Vol: 91 Nbr: Abs: Pg: 1845-1853

0 2 supply and demand limitatons to oxidative metabolism: evidence from 31 P MRS of active and sedentary humans.
Periodical: American Journal of Physiology Index Medicus:
Authors: Haseler LJ, Lin AP, and Richardson RS ART
Yr: 0 Vol: Nbr: Abs: Pg:

Short-term exercise training of skeletal muscle: the matabolic response in young and older adults.
Periodical: Medicine and Science in Sports and Exercise Index Medicus:
Authors: Richardson RS, Camargo M, Brown CF, Haseler LJ ABS
Yr: 2003 Vol: 35 Nbr: 5 Abs: s600 Pg:

Evolving techniques for the investigation of muscle bioenergetics and oxygenation.
Periodical: Biochemical Society Transactions Index Medicus:
Authors: Richardson RS, Noyszewski EA, Haseler LJ, Bluml S, Frank LF ART
Yr: 2002 Vol: 30 Nbr: Abs: Pg: 232-237

Reduced skeletal muscle oxidative efficiency in COPD, but normal peak VO2.
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Richardson RS< Leek BT, Gavin TP, Haseler LJ, Mudaliar SRD, Henry R, Ries AL, et al. ART
Yr: 2003 Vol: 169 Nbr: Abs: Pg: 89-96

Skeletal muscle oxidative metabolism in sedentary humans.
Periodical: American Journal of Physiology Index Medicus:
Authors: Haseler LJ, Lin A, Richardson RS ART
Yr: 2004 Vol: 97 Nbr: Abs: Pg: 1077 - 1081

The role O2 in determining phosphocreatine onset kinetics in exercising humans.
Periodical: Journal of Physiology Index Medicus:
Authors: Haseler LJ, Kindig CA, Richardson RS, Hogan MC ART
Yr: 2004 Vol: 558 Nbr: 3 Abs: Pg: 985 - 992

Incomplete restoration of PCr following exercise relates to degree of ischemia.
Periodical: Medicine and Science in Sports and Exercise Index Medicus:
Authors: Haseler LJ, Lin AP, Greene DR, Richardson RS ABS
Yr: 2001 Vol: 31 Nbr: Abs: Pg: S278

Metabolic adaptations in young and old subjects to short-term training.
Periodical: Society for Magnetic Resonance in Medicine Proceedings Index Medicus:
Authors: Richardson RS, Camargo M, Brown CF, Haseler LJ ABS
Yr: 2003 Vol: 35 Nbr: Abs: Pg: S110

Phosphocreatine onset and recovery kinetics in aging skeletal muscle: effect of short term endurance training.
Periodical: Medicine and Science in Sports and Exercise Index Medicus:
Authors: Haseler LJ, Hoff J, Camargo M, Richardson RS ABS
Yr: 2004 Vol: 36 Nbr: Abs: Pg: S358

Effect of exercise and hyperoxia on skeletal muscle metabolism in COPD.
Periodical: Medicine and Science in Sports and Exercise Index Medicus:
Authors: Uberoi A, Warner M, Haseler LJ, Richardson RS ABS
Yr: 2004 Vol: 36 Nbr: Abs: Pg: S210

Effect of varied FIO2 on phosphocreatine hydrolysis at exercise onset in humans.
Periodical: Medicine and Science in Sports and Exercise Index Medicus:
Authors: Hogan MC, Kindig CA, Richardson RS, Haseler LJ ABS
Yr: 0 Vol: Nbr: Abs: Pg:

Effects of small muscle mass short term endurance training on phosphocreatine sparing and recovery.
Periodical: Medicine and Science in Sports and Exercise Index Medicus:
Authors: Brown CF, Haseler LJ, Hoff J, Camargo M, Richardson RS ART
Yr: 2002 Vol: 34 Nbr: Abs: Pg: S241