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 V̇O2 (V̇O2p) 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 V̇O2 (V̇O2m) recovery kinetics following MOD; and (ii) ex vivo by high-resolution 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 V̇O2p (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 V̇O2p (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 V̇O2p 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 V̇O2m 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