Short-term Bed Rest Exposure Impairs Peripheral Vascular And Endothelial Functions Whereas Mitochondrial Respiration Is Unaffected

Abstract

PURPOSE: Impairments of oxidative metabolism after exposure to microgravity are documented, but the sites of impairment are still debated. Aim of this study was to identify markers of impaired oxidative metabolism along the O2 pathway, following 10-day of horizontal bed rest (BR). METHODS: fore (PRE) and after (POST) BR, 10 young males performed on a cycle ergometer an incremental exercise (to determine peak pulmonary V̇O2 [V̇O2p] and peak cardiac output [CO]), and moderate-intensity exercise (MOD). Vastus lateralis muscle fractional O2 extraction was measured by near-infrared spectroscopy (NIRS). Blood flow response was evaluated in the common femoral artery by Eco-Doppler during 1-min passive leg movements (PLM). Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in isolated muscle fibers obtained by biopsy, and non-invasively in vivo by NIRS, by calculating skeletal muscle V̇O2 (V̇O2m) recovery kinetics (repeated occlusions method) following MOD. Resting V̇O2m was estimated by NIRS by the rate of muscle oxygenation during limb blood flow occlusions at rest. RESULTS: Peak V̇O2p and peak cardiac output were lower in POST vs. PRE (41.5 ± 6.5 ml/kg/min vs. 44.5 ± 7.4, P = 0.001; 19.0 ± 3.2 L/min vs. 25.2 ± 5.5, P = 0.004). 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, estimate of mitochondrial mass, was not different (P = 0.115) in POST (131.2 ± 15.9 UI/mg) vs. PRE (137.9 ± 18.8). Maximal ADP-stimulated mitochondrial respiration (66.4 ± 17.5 pmol/s/mg [POST] vs. 72.3 ± 14.0 [PRE], P = 0.127) was not affected by BR. Apparent Km for ADP sensitivity was reduced in POST vs. PRE (P = 0.04). The time-constant of V̇O2m recovery was not different (P = 0.079) in POST (22.2 ± 5.9 s) vs. PRE (21.7 ± 5.7). V̇O2m at rest was reduced by about 25% in POST vs. PRE (P < 0.01). CONCLUSIONS: Cardiovascular and peripheral vascular-endothelial functions were impaired following a 10-day BR, whereas mitochondrial mass and function (both in vivo and ex vivo) were unaffected, or even improved (enhanced mitochondrial sensitivity to submaximal [ADP]). Resting V̇O2m was lower after BR; muscle catabolic processes induced by BR are less energy-consuming than anabolic ones. Funding: ASI, MARS-PRE, n. DC-VUM-2017-006.