Abstract
ObjectiveDisuse atrophy (DA) describes inactivity-induced skeletal muscle loss, through incompletely defined mechanisms. An intriguing observation is that individual muscles exhibit differing degrees of atrophy, despite exhibiting similar anatomical function/locations. We aimed to develop an innovative experimental paradigm to investigate Atrophy Resistant tibialis anterior (TA) and Atrophy Susceptible medial gastrocnemius (MG) muscles (aRaS) with a future view of uncovering central mechanisms.MethodSeven healthy young men (22 ± 1 year) underwent 15 days unilateral leg immobilisation (ULI). Participants had a single leg immobilised using a knee brace and air-boot to fix the leg (75° knee flexion) and ankle in place. Dual-energy X-ray absorptiometry (DXA), MRI and ultrasound scans of the lower leg were taken before and after the immobilisation period to determine changes in muscle mass. Techniques were developed for conchotome and microneedle TA/MG muscle biopsies following immobilisation (both limbs), and preliminary fibre typing analyses was conducted.ResultsTA/MG muscles displayed comparable fibre type distribution of predominantly type I fibres (TA 67 ± 7%, MG 63 ± 5%). Following 15 days immobilisation, MG muscle volume (–2.8 ± 1.4%, p < 0.05) and muscle thickness decreased (−12.9 ± 1.6%, p < 0.01), with a positive correlation between changes in muscle volume and thickness (R2 = 0.31, p = 0.038). Importantly, both TA muscle volume and thickness remained unchanged.ConclusionThe use of this unique “aRaS” paradigm provides an effective and convenient means by which to study the mechanistic basis of divergent DA susceptibility in humans, which may facilitate new mechanistic insights, and by extension, mitigation of skeletal muscle atrophy during human DA.
Highlights
Skeletal muscle disuse atrophy (DA), manifesting as a loss of muscle mass, occurs for clinically important reasons such as sedentary behaviour, hospitalisation, enforced bed-rest or limb immobilisation for the purposes of recovery after illness or injury
Fibre Type Distribution and Body Composition. Both non-immobilised tibialis anterior (TA) and medial gastrocnemius (MG) were predominantly comprised of type I fibres (TA 67 ± 3%, MG 63% ± 3; Figures 2A–C)
Prior to Unilateral limb immobilisation (ULI), there were no differences between legs for either lower leg fat free mass (FFM) or lean mass
Summary
Skeletal muscle disuse atrophy (DA), manifesting as a loss of muscle mass, occurs for clinically important reasons such as sedentary behaviour, hospitalisation, enforced bed-rest or limb immobilisation for the purposes of recovery after illness or injury. Head-down bed rest models of unloading have demonstrated similar degrees of muscle loss (Trappe S. et al, 2004; Rittweger et al, 2005), with ∼17% loss of quadriceps volume after 84 days (Trappe S. et al, 2004). Unilateral limb immobilisation (ULI) either by casting or suspension (ULLS) (de Boer et al, 2007; Wall et al, 2014), induce considerable muscle loss, with quadriceps CSA decreasing by 3.5% in healthy young men after just 5 days of ULI by casting (Dirks et al, 2014). After 14 days ULI, muscle loss has been shown to progress to an ∼8% decline in both CSA (Wall et al, 2014) and volume (Dirks et al, 2014). ULI provides advantages over bed-rest models, whereby the non-immobilised weight-bearing limb provides an internal control, and does not induce systemic deconditioning which may introduce confounders such as cardiovascular decline (Krasnoff and Painter, 1999)
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