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

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 O-2 uptake ((V) over dotO(2)) and vastus lateralis fractional O-2 extraction (changes in deoxygenated hemoglobin + myoglobin concentration, Delta[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 (V) over dotO(2peak) and Delta[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 Delta[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 O-2 delivery and upstream of mitochondrial function, possibly at the level of the intramuscular matching between O-2 supply and utilization and peripheral O-2 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.