Hypoxia Aggravates Inactivity-Related Muscle Wasting

Abstract

Poor musculoskeletal state is commonly observed in numerous clinical populations such as chronic obstructive pulmonary disease (COPD) and heart failure patients. It, however, remains unresolved whether systemic hypoxemia, typically associated with such clinical conditions, directly contributes to muscle deterioration. We aimed to experimentally elucidate the effects of systemic environmental hypoxia upon inactivity-related muscle wasting. For this purpose, fourteen healthy, male participants underwent three 21-day long interventions in a randomized, cross-over designed manner: (i) bed rest in normoxia (NBR; P_iO₂ = 133.1 ± 0.3 mmHg), (ii) bed rest in normobaric hypoxia (HBR; P_iO₂ = 90.0 ± 0.4 mmHg) and ambulatory confinement in normobaric hypoxia (HAmb; P_iO₂ = 90.0 ± 0.4 mmHg). Peripheral quantitative computed tomography and vastus lateralis muscle biopsies were performed before and after the interventions to obtain thigh and calf muscle cross-sectional areas and muscle fiber phenotype changes, respectively. A significant reduction of thigh muscle size following NBR (-6.9%, SE 0.8%; P < 0.001) was further aggravated following HBR (-9.7%, SE 1.2%; P = 0.027). Bed rest-induced muscle wasting in the calf was, by contrast, not exacerbated by hypoxic conditions (P = 0.47). Reductions in both thigh (-2.7%, SE 1.1%, P = 0.017) and calf (-3.3%, SE 0.7%, P < 0.001) muscle size were noted following HAmb. A significant and comparable increase in type 2× fiber percentage of the vastus lateralis muscle was noted following both bed rest interventions (NBR = +3.1%, SE 2.6%, HBR = +3.9%, SE 2.7%, P < 0.05). Collectively, these data indicate that hypoxia can exacerbate inactivity-related muscle wasting in healthy active participants and moreover suggest that the combination of both, hypoxemia and lack of activity, as seen in COPD patients, might be particularly harmful for muscle tissue.

Keywords: bed rest; fiber type; hypoxemia; muscle loss; vastus lateralis.

FIGURE 1

Cross-over designed allocation of the 14 participants (P1–P14) to the respective interventions (NBR, normoxic bed rest; HBR, hypoxic bed rest; HAmb, hypoxic ambulation) during the course of the project.

FIGURE 2

Thigh (A) and Calf (B) muscle cross-sectional area changes after two (D2), ten (D10), and twenty-one (D21) days of normoxic bed rest (NBR; blue), hypoxic bed rest (HBR; red) and hypoxic ambulation (HAmb; green) interventions, as well as 14 days post (R+14). Data are presented as Means ± SE. ^∗(p < 0.05) and ^∗∗∗(p < 0.001) denote significant reductions compared to baseline. + (p < 0.05) denotes significant difference between the two bed rest interventions.

FIGURE 3

Type 1, type 2a, and type 2× fiber changes within the vastus lateralis muscle following normoxic bed rest (NBR), hypoxic bed rest (HBR), and hypoxic ambulation (HAmb) interventions. Data are presented as means ± SE. ^∗(p < 0.05) denotes significant difference compared to baseline.