PlanHab*: Hypoxia does not worsen the impairment of skeletal muscle oxidative function induced by bed rest alone

Key points Superposition of hypoxia on 21 day bed rest did not worsen the impairment of skeletal muscle oxidative function induced by bed rest alone. A significant impairment of maximal oxidative performance was identified downstream of cardiovascular O2 delivery, involving both the intramuscular matching between O2 supply and utilization and mitochondrial respiration. These chronic adaptations appear to be relevant in terms of exposure to spaceflights and reduced gravity habitats (Moon or Mars), as characterized by low gravity and hypoxia, in patients with chronic diseases characterized by hypomobility/immobility and hypoxia, as well as in ageing. Abstract Skeletal muscle oxidative function was evaluated in 11 healthy males (mean \ub1 SD age 27 \ub1 5 years) prior to (baseline data collection, BDC) and following a 21 day horizontal bed rest (BR), carried out in normoxia (urn:x-wiley:00223751:media:tjp12878:tjp12878-math-0001 = 133 mmHg; N\u2010BR) and hypoxia (urn:x-wiley:00223751:media:tjp12878:tjp12878-math-0002 = 90 mmHg; H\u2010BR). H\u2010BR was aimed at simulating reduced gravity habitats. The effects of a 21 day hypoxic ambulatory confinement (urn:x-wiley:00223751:media:tjp12878:tjp12878-math-0003 = 90 mmHg; H\u2010AMB) were also assessed. Pulmonary O2 uptake (urn:x-wiley:00223751:media:tjp12878:tjp12878-math-0004), vastus lateralis fractional O2 extraction (changes in deoxygenated haemoglobin + myoglobin concentration, \u394[deoxy(Hb + Mb)]; near\u2010infrared spectroscopy) and femoral artery blood flow (ultrasound Doppler) were evaluated during incremental one\u2010leg knee\u2010extension exercise (reduced constraints to cardiovascular O2 delivery) carried out to voluntary exhaustion in a normoxic environment. Mitochondrial respiration was evaluated ex vivo by high\u2010resolution respirometry in permeabilized vastus lateralis fibres. urn:x-wiley:00223751:media:tjp12878:tjp12878-math-0005 decreased (P < 0.05) after N\u2010BR (0.98 \ub1 0.13 L min 121) and H\u2010BR (0.96 \ub1 0.17 L min 121) vs. BDC (1.05 \ub1 0.14 L min 121). In the presence of a decreased (by 3c6\u20138%) thigh muscle volume, urn:x-wiley:00223751:media:tjp12878:tjp12878-math-0006 normalized per unit of muscle mass was not affected by both interventions. \u394[deoxy(Hb + Mb)]peak decreased (P < 0.05) after N\u2010BR (65 \ub1 13% of limb ischaemia) and H\u2010BR (62 \ub1 12%) vs. BDC (73 \ub1 13%). H\u2010AMB did not alter urn:x-wiley:00223751:media:tjp12878:tjp12878-math-0007 or \u394[deoxy(Hb + Mb)]peak. An overshoot of \u394[deoxy(Hb + Mb)] was evident during the first minute of unloaded exercise after N\u2010BR and H\u2010BR. Arterial blood flow to the lower limb during both unloaded and peak knee extension was not affected by any intervention. Maximal ADP\u2010stimulated mitochondrial respiration decreased (P < 0.05) after all interventions vs. control. In 21 day N\u2010BR, a significant impairment of oxidative metabolism occurred downstream of cardiovascular O2 delivery, affecting both mitochondrial respiration and presumably the intramuscular matching between O2 supply and utilization. Superposition of H on BR did not worsen the impairment induced by BR alone