Acute disuse muscle atrophy in health and disease: an investigation of the timecourse, functional effects and a potential treatment strategy

Purpose Maintenance of skeletal muscle mass and function is essential for a healthy, long life. Episodes of reduced mobility may be associated with significant disuse muscle atrophy (DMA) and loss of function. It is increasingly suggested that the cumulative effect of these episodes through later life may be a major driver behind the development of sarcopenia. The purpose of this thesis was therefore to investigate the timecourse of DMA in a range of human lower limb muscles, how this varies over the period of immobilisation and between muscles, and its functional outcomes. Furthermore, the impact of associated ill health on these findings was investigated, as well as the effectiveness of neuromuscular electrical stimulation (NMES) in attenuating muscle loss. Methods Systematic review and meta-analysis of studies reporting measurement of muscle mass at repeated timepoints during a period of immobilisation, casting following bone fracture, and critical care admission was completed, with data synthesised to characterise the timecourse of DMA in leg muscles. Following this, two studies were conducted in which healthy young men were recruited to have unilateral lower limb immobilisation (ULLI) using a knee brace and ankle boot for five or 15 days. Measurement of muscle mass and function were completed at various timepoints. Measurements of muscle mass were made using MRI (gold standard) and ultrasound, in order to validate the use of ultrasound in the detection and monitoring of DMA. Finally, a split leg randomised control trial of patients undergoing major abdominal surgery was completed. In this study, the control limb was used to characterise the degree of loss of muscle mass and function in an immobilised and unwell cohort, whilst the other limb underwent twice daily NMES to investigate its efficacy in attenuating loss of muscle mass and function. Results Systematic review and meta-analysis demonstrated rapid loss of muscle mass, with greater losses in individuals immobilised after bone fracture or due to ...