Abstract
To evaluate the individual responses in skeletal muscle outcomes following bed rest, data from three studies (21-day PlanHab; 10-day FemHab and LunHab) were combined. Subjects (n = 35) participated in three cross-over campaigns within each study: normoxic (NBR) and hypoxic bed rest (HBR), and hypoxic ambulation (HAMB; used as control). Individual variability (SDIR) was investigated as √(SD–SD), where SDExp and SDCon are the standard deviations of the change score (i.e., post – pre) in the experimental (NBR and HBR) and the control (HAMB) groups, respectively. Repeatability and moderators of the individual variability were explored. Significant SDIR was detected for knee extension torque, and thigh and calf muscle area, which translated into an individual response ranging from 3 to −17% for knee extension torque, −2 to −12% for calf muscle area, and −1 to −8% for thigh muscle area. Strong correlations were found for changes in NBR vs. HBR (i.e., repeatability) in thigh and calf muscle area (r = 0.65–0.75, P < 0.0001). Change-scores in knee extension torque, and thigh and calf muscle area strongly correlated with baseline values (P < 0.001; r between −0.5 and −0.9). Orthogonal partial least squares regression analysis explored if changes in the investigated variables could predict calf muscle area alterations. This analysis indicated that 43% of the variance in calf muscle area could be attributed to changes in all of the other variables. This is the first study using a validated methodology to report clinically relevant individual variability after bed rest in knee extension torque, calf muscle area, and (to a lower extent) thigh muscle area. Baseline values emerged as a moderator of the individual response, and a global bed rest signature served as a moderately strong predictor of the individual variation in calf muscle area alterations.
Highlights
Interindividual differences in the physiological responses to an intervention have received great research attention in the last decades with the aim to identify “responders” and “non-responders,” to explore the mechanisms that influence the individual responsiveness, and to promote “personalized medicine” (Mann et al, 2014; Hecksteden et al, 2015; Ross et al, 2019)
After filtering for inclusion criteria, the number of participants included in the database was 35, with 9 in FemHab, 12 in LunHab, and 14 in PlanHab
The main finding of this study is that there was clinically relevant individual variability in knee extension (KE) torque, and calf and thigh muscle area, and this individual response was repeatable across bed rest interventions, at least for muscle mass readouts
Summary
Interindividual differences in the physiological responses to an intervention (e.g., exercise or drugs) have received great research attention in the last decades with the aim to identify “responders” and “non-responders,” to explore the mechanisms that influence the individual responsiveness, and to promote “personalized medicine” (Mann et al, 2014; Hecksteden et al, 2015; Ross et al, 2019). Some of the approaches used to analyze individual variability have not taken into account the variability explained by technical and/or random errors, and have not reported biological variability alone (Atkinson and Batterham, 2015) Controlling for these factors is essential for the accurate determination of the true individual response to an intervention (Atkinson and Batterham, 2015; Atkinson et al, 2019). The use of cross-over designs with complete wash-out periods between intervention/control stages can be very helpful, since they offer the advantage of controlling for genetic factors influencing the individual response. It follows that only when an individual response is confirmed, potential factors (i.e., moderators or mediators) that may influence the observed individual response can be explored
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