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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
22
300 eccentric contractions of the knee extensors
University of Exeter
Exeter, Devon, United Kingdom
Change in thigh muscle volume from pre-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.
Time frame: After 2 days of immobilisation
Change in thigh muscle volume from pre-immobilisation
The volume of the muscles comprising the thigh after 7 days of immobilisation will be compared to pre-immobilisation values, and values obtained after 2 days of immobilisation. This will be measured using MRI.
Time frame: After 7 days of immobilisation
Change in unilateral knee extensor 1 repetition maximum
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
Time frame: After 7 days of immobilisation
Change in unilateral knee extensor maximal voluntary torque production
Unilateral knee extensor maximal voluntary torque production will be measured before and after 7 days of single leg immobilisation using an isokinetic dynamometer.
Time frame: After 7 days of immobilisation
Change in unilateral knee extensor isokinetic total work
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.
Time frame: After 7 days of immobilisation
Muscle protein synthesis assessed using the stable isotope Deuterium Oxide
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).
Time frame: After 2 days of immobilisation
Muscle protein synthesis assessed using the stable isotope Deuterium Oxide
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 7 days of immobilisation will be used to calculated a fractional synthetic rate (% day).
Time frame: After 7 days of immobilisation
Change in skeletal muscle gene expression
Skeletal muscle gene expression will be measured before and after 2 days of single leg immobilisation.
Time frame: After 2 days of immobilisation
Change in skeletal muscle gene expression
Skeletal muscle gene expression will be measured before and after 7 days of single leg immobilisation.
Time frame: After 7 days of immobilisation
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