Muscle Atrophy Following Bedrest Improves Oxygen Diffusion, But Does Not Compensate For Mitochondrial Impairment

INTRODUCTION: Prolonged bedrest (BR) is associated with a progressive loss of muscle oxidative capacity[1], muscle atrophy and capillary rarefaction, but the time courses of these changes differ [2,3]. It is unknown whether muscle atrophy following BR ameliorates the effects of these muscle adaptations to BR, thereby protecting against loss of muscle O2 diffusive flow and maximal muscle O2utilization. We hypothesized that 21 days of BR would be associated with increased muscle O2 diffusive flow, and ameliorate loss of maximal muscle O2 utilization. METHODS: Nine young males (23 ± 4 yr; 80 ± 7 kg; 182 ± 6 cm) underwent 21 days BR. Vastus lateralis muscle cross section area (CSA) was measured by magnetic resonance at mid-thigh. Vastus lateralis muscle O2 uptake recovery rate constant (k), calculated from tissue oxygen saturation index (TSI) slope during repeated occlusions performed immediately after leg-extension exercise, was assessed before (preBR)and after (postBR). Time of ischemia-reperfusion for the occlusions was manipulated to maintain TSI in both non-limiting (kHIGH) and limiting (kLOW) O2 availability conditions of the physiological TSI normalization (PN). kHIGH was used to assess muscle oxidative capacity, and the value of kLOW/TSILOW was used as a surrogate of muscle O2 diffusing capacity (DmO2). RESULTS: CSA was 12% lower after BR (89.4 ± 11.0 vs. 78.7 ± 9.7 cm2; p = 0.01). kHIGH was measured at 57 ± 3% of the PN in both preBR and postBR. kLOW was measured at 26 ± 11% and 22 ± 6% of PN during preBR and postBR measurements, respectively. kHIGH was 12% less after BR (2.22 ± 0.43 vs. 1.95 ± 0.35 min-1; p = 0.001). kLOW was not different after BR (1.57 ± 0.20 vs. 1.69 ± 0.42 min-1; p = 0.365). The value of kLOW/TSILOW (reflecting DmO2) was significantly increased after BR (0.060 ± 0.003 vs. 0.077 ± 0.006 %-1.min-1;p = 0.002). CONCLUSIONS: In young participants, 21 days BR reduced muscle oxidative capacity. However, higher muscle O2 diffusive flow contributed to ameliorating the decline in maximal muscle O2 utilization. Further work is needed to identify whether muscle atrophy and an increase in the capillary supply region contributed to increased DmO2 following BR. Project was supported by "The countermeasures to the neuromuscular impairments induced by inactivity and disuse across different ages (ReActive-AGE)" PRIN PNRR - P2022FNCPR