Muscle Damage and Disuse Atrophy

Not Applicable

Completed

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.

Recruitment & Eligibility

Inclusion Criteria

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.

Arm && Interventions

Group	Intervention	Description
Muscle damage	Eccentric exercise	300 bilateral knee extensor eccentric contraction performed immediately prior to immobilisation

Primary Outcome Measures

Name	Time	Method
Change in thigh muscle volume from pre-immobilisation	After 7 days of 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.

Secondary Outcome Measures

Name	Time	Method
Change in skeletal muscle gene expression	After 7 days of immobilisation	Skeletal muscle gene expression will be measured before and after 7 days of single leg immobilisation.
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 7 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 7 days of immobilisation will be used to calculated a fractional synthetic rate (% day).
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

Receive instant email notifications about changes in this clinical trial

Receive instant email notifications about changes in this clinical trial