Microvascular/endothelial Dysfunction, Preserved Mitochondrial Respiration, Increased H2O2Emissionin Young And Elderly Following Bed Rest

PURPOSE: This study examined potential limitations in oxygen transport and utilization during exercise after various durations of horizontal bed rest (BR) in healthy individuals of different ages. METHODS: Ten and 9 young (Y) males (23±4 years) were tested before (PRE) and after 10 (POST10) and 21 (POST21) days of BR, respectively. Ten elderly (69±3 years) males were tested only in PRE and POST10. Participants performed an incremental exercise to determine peak pulmonary V̇ O2 (V̇ O2p) and a constant work rate exercise (MOD). Microvascular/endothelial function was evaluated during 1-min passive leg movements (PLM). Mitochondrial respiration was evaluated: (i) non-invasively in vivo by near-infrared spectroscopy (NIRS) by calculating skeletal muscle V̇ O2 (V̇ O2m) recovery kinetics following MOD; and (ii) ex vivo by highresolution respirometry (maximal ADP-stimulated mitochondrial respiration, OXPHOS). Maximal mitochondrial hydrogen peroxide (H2O2) production and changes in H2O2 emission across a range of [ADP] were also evaluated. RESULTS: In Y, peak V̇ O2p (40.0 ± 2.5 ml.kg-1.min-1 in PRE) was 8% lower (P=0.02) in POST10 and 10% lower in POST21. In E, peak V̇ O2p (24.3 ± 7.8 ml.kg-1.min-1 in PRE) was 5% lower (P=0.02) in POST10. In Y, the area under the blood flow vs time curve (AUC) during PLM was lower (P=0.04) in POST10 (274 ± 233 mL) and POST21 (160 ± 51) vs PRE (367 ± 167). In E AUC in POST10 (109 ± 60) was lower vs PRE (153 ± 89) (P=0.04). The percentage decreases in peak V̇ O2p and AUC between Y and E in POST10 were not different (P>0.05). In both Y (PRE=25.7 ± 5.5 s) and E (PRE=38.2 ± 16.3), τ of V̇ O2m recovery was not affected by any BR intervention (P>0.05). In both Y (PRE=55.1 ± 15.1 pmol.s-1.mg-1) and E (PRE=41.1 ± 14.3), OXPHOS was not affected by any BR intervention (P>0.05). The ratio between mitochondrial H2O2 emission and mitochondrial O2 flux increased in E in POST10 (+62%; P=0.01), whereas it remained unchanged in Y (P>0.05). In Y, however, an increased H2O2 emission in the presence of submaximal ADP concentrations was observed in POST21 (P<0.05). CONCLUSIONS: Both Y and E showed a decline in peak aerobic and microvascular functions after 10 and 21 days of BR; the percentage decreases were similar in both age groups. Both groups showed preserved mitochondrial respiration but increased mitochondrial H2O2emission. Supported by: MUR; PRIN Project 2020EM9A