The Impairment Of Oxidative Metabolism After 10-day Of Bed Rest Is Upstream Of Skeletal-Muscle Mitochondria

Abstract

PURPOSE: Exposure to microgravity, as simulated by bed rest (BR), leads to an impairment of oxidative metabolism. The sites of this impairment are still debated. Aim of this study was to identify markers of impaired oxidative metabolism along the O2 pathway, from ambient air to skeletal muscle mitochondria, following 10 days of BR. METHODS: Measurements were carried out on 10 recreationally active young males (age 23 ± 5 years [mean±SD]) before (PRE) and after (POST) 10 days of horizontal BR. Pulmonary O2 uptake (V̇O2) and other respiratory, cardiovascular and skeletal muscle variables were determined during an incremental exercise on a cycle ergometer. Peripheral vascular and endothelial functions were evaluated by the blood flow response (Doppler ultrasound) in the femoral artery during 1-min passive leg movement (PLM). Mitochondrial respiration was evaluated by high-resolution respirometry on permeabilized vastus lateralis fibers obtained by biopsy. RESULTS: Peak V̇O2 was lower (P=0.001) in POST (41.5 ± 6.5 ml.kg-1.min-1) vs. PRE (44.5 ± 7.4). The area under the blood flow vs. time curve during PLM was lower (P=0.038) in POST (274 ± 233 mL) vs. PRE (427 ± 291). Skeletal muscle citrate synthase activity, an estimate of mitochondrial mass, was not different (P=0.115) in POST (131.2 ± 15.9 UI.mg-1.protein) vs. PRE (137.9 ± 18.8). Maximal ADP-stimulated mitochondrial respiration (66.4 ± 17.5 pmol.s-1.mg-1 wet weight [POST] vs. 72.3 ± 14.0 [PRE], P=0.127) and oxidative phosphorylation coupling efficiency (respiratory control ratio, 4.10 ± 1.19 [PRE] vs. 3.59 ± 1.11 [POST], P=0.443) were not affected by BR. CONCLUSIONS: These preliminary data suggest that the whole-body impairment of oxidative metabolism during exercise, following 10 days of horizontal BR, is associated with an impairment of peripheral vascular and endothelial functions, whereas mitochondrial volume and respiratory function are unaffected. Data related to several other markers (pulmonary function, cardiac output, submaximal exercise tolerance, skeletal muscle fractional O2 extraction, skeletal muscle V̇O2 recovery kinetics, mitochondrial respiration sensitivity to submaximal [ADP]) are yet to be analyzed. Funding: ASI, MARS-PRE Project, n. DC-VUM-2017-006