title: Separate and combined effects of a 10-d exposure to hypoxia and inactivity on oxidative function in vivo and mitochondrial respiration ex vivo in humans.
abstract: An integrative evaluation of oxidative metabolism was carried out in 9 healthy young men (age, 24.1 ± 1.7 yr mean ± SD) before (CTRL) and after a 10-day horizontal bed rest carried out in normoxia (N-BR) or hypoxia (H-BR, FiO2 = 0.147). H-BR was designed to simulate planetary habitats. Pulmonary O2 uptake (V̇o2) and vastus lateralis fractional O2 extraction (changes in deoxygenated hemoglobin+myoglobin concentration, Δ[deoxy(Hb+Mb)] evaluated using near-infrared spectroscopy) were evaluated in normoxia and during an incremental cycle ergometer (CE) and one-leg knee extension (KE) exercise (aimed at reducing cardiovascular constraints to oxidative function). Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers. During CE V̇o2peak and Δ[deoxy(Hb+Mb)]peak were lower (P < 0.05) after both N-BR and H-BR than during CTRL; during KE the variables were lower after N-BR but not after H-BR. During CE the overshoot of Δ[deoxy(Hb+Mb)] during constant work rate exercise was greater in N-BR and H-BR than CTRL, whereas during KE a significant difference vs. CTRL was observed only after N-BR. Maximal mitochondrial respiration determined ex vivo was not affected by either intervention. In N-BR, a significant impairment of oxidative metabolism occurred downstream of central cardiovascular O2 delivery and upstream of mitochondrial function, possibly at the level of the intramuscular matching between O2 supply and utilization and peripheral O2 diffusion. Superposition of hypoxia on bed rest did not aggravate, and partially reversed, the impairment of muscle oxidative function in vivo induced by bed rest. The effects of longer exposures will have to be determined.
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy;
authors.forename: Desy
authors.initials: D
authors.lastname: Salvadego
authors.affiliation: Department of Environmental Physiology, Swedish Aerospace Physiology Centre, Royal Institute of Technology, Stockholm, Sweden;
authors.forename: Michail E
authors.initials: ME
authors.lastname: Keramidas
authors.affiliation: Department of Molecular Medicine, University of Pavia, Italy;
authors.forename: Lorenza
authors.initials: L
authors.lastname: Brocca
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy;
authors.forename: Rossana
authors.initials: R
authors.lastname: Domenis
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy;
authors.forename: Irene
authors.initials: I
authors.lastname: Mavelli
authors.affiliation: Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany; Children's Hospital, Medical Faculty, University of Cologne, Germany;
authors.forename: Jörn
authors.initials: J
authors.lastname: Rittweger
authors.affiliation: Department of Environmental Physiology, Swedish Aerospace Physiology Centre, Royal Institute of Technology, Stockholm, Sweden;
authors.forename: Ola
authors.initials: O
authors.lastname: Eiken
authors.affiliation: Department of Automation, Biocybernetics and Robotics, Jožef Stefan Institute, Ljubljana, Slovenia; and.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Mekjavic
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy; Institute of Bioimaging and Molecular Physiology, National Research Council, Milano, Italy bruno.grassi@uniud.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Grassi
mesh_terms: D000328:Adult; D001510:Bed Rest / Q000379:methods; D019069:Cell Respiration / Q000502:physiology*; D015444:Exercise / Q000502:physiology; D005080:Exercise Test / Q000379:methods; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009211:Myoglobin / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D052097:Quadriceps Muscle / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D009211:Myoglobin; C100003:deoxyhemoglobin; D010100:Oxygen
keywords: hypoxia; microgravity; mitochondrial respiration; muscle inactivity; oxidative function