Muscle Disuse Atrophy
Conditions
Keywords
Muscle damage, Inflammation, Immobilisation
Brief summary
Limb injury generally requires a period of recovery during which time the limb is often immobilised (e.g. with a cast or brace) resulting in a rapid loss of skeletal muscle. Despite the importance of muscle loss during injury, our understanding of how it occurs is incomplete. Several factors are likely to contribute, including a lack of muscle contraction and injury induced inflammation. In this study, the investigators will recruit healthy volunteers who will spend 7 days in a knee brace to replicate leg immobilisation. Prior to immobilisation, half of the participants will perform a single session of strenuous resistance exercise which is known to cause muscle damage and initiate an inflammatory response. This is designed to replicate the muscle damage and inflammation that occurs with injury. The remaining half of participants will not perform this exercise, allowing us to look at the additive effect of muscle damage and inflammation on muscle loss with immobilisation.
Interventions
PROCEDUREEccentric exercise
300 eccentric contractions of the knee extensors
Sponsors
University of Exeter
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 18 - 40 * BMI between 18 and 27 * Healthy, recreationally active, non smoker
Exclusion criteria
* Non-removable metallic implants (including heart pacemaker, cochlear implants, medication pumps, surgical clips, plates or screws) or claustrophobia * Use of nutritional supplements * Chronic use of over the counter medication * Any diagnosed metabolic disease (e.g. type 1 or 2 Diabetes). * Any diagnosed cardiovascular disease or hypertension. * Anyone with previous motor disorders. Anyone with a current musculoskeletal injury that may impair their use of crutches.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in thigh muscle volume from pre-immobilisation | After 2 days of immobilisation | The volume of the muscles comprising the thigh after 2 days of immobilisation will be compared to pre-immobilisation values. This will be measured using MRI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in unilateral knee extensor 1 repetition maximum | After 7 days of immobilisation | Unilateral knee extensor 1 repetition maximum will be measured before and after 7 days of single leg immobilisation using a weight stack leg extension machine |
| Change in unilateral knee extensor maximal voluntary torque production | After 7 days of immobilisation | Unilateral knee extensor maximal voluntary torque production will be measured before and after 7 days of single leg immobilisation using an isokinetic dynamometer. |
| Change in unilateral knee extensor isokinetic total work | After 7 days of immobilisation | Unilateral knee extensor total isokinetic work after 30 consecutive contractions will be measured before and after 7 days of single leg immobilisation using an isokinetic dynamometer. |
| Muscle protein synthesis assessed using the stable isotope Deuterium Oxide | After 2 days of immobilisation | The enrichment of deuterated alanine (from the deuterium oxide heavy water stable isotope tracer) in vastus lateralis biopsy samples will be measured relative to the non-deuterated alanine. The change between pre-immobilisation and 2 days of immobilisation will be used to calculated a fractional synthetic rate (% day). |
| Change in skeletal muscle gene expression | After 2 days of immobilisation | Skeletal muscle gene expression will be measured before and after 2 days of single leg immobilisation. |
Countries
United Kingdom
Outcome results
None listed