Hardy, Edward John Oliver
(2023)
Acute disuse muscle atrophy in health and disease: an investigation of the timecourse, functional effects and a potential treatment strategy.
PhD thesis, University of Nottingham.
Abstract
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 critical illness. Rates of DMA appeared greatest during the first two weeks of immobilisation and to vary between muscles, however there were insufficient data to fully characterise these trends. Studies of healthy individuals undergoing two weeks of ULLI identified vastus lateralis (VL) and medial gastrocnemius (MG) as atrophy susceptible (aS) muscles, with significant decrease in muscle mass after just five days. Tibialis anterior (TA) was identified as an atrophy resistant (aR) muscle, with no significant change in muscle mass after 15 days of ULLI. Muscle strength and power also decreased in VL and MG, with a 20-30% reduction in maximum voluntary contraction (MVC) after 15 days, whereas no significant change was identified in TA MVC. Loss of VL CSA (-9.16%) and knee extension strength (-19.7%) in postoperative patients was more rapid than in healthy individuals. However, use of NMES reduced these losses by approximately 50%, suggesting it is a promising therapeutic intervention to reduce muscle loss in individuals with reduced mobility.
Conclusion
During immobilisation there is rapid and significant loss of muscle mass and function. These losses are compounded in individuals who are unwell or recovering after surgery. The rate at which muscle mass and function is lost varies between muscles, with the greatest losses in functionally important muscles for standing and walking. NMES significantly attenuates the loss of muscle mass in postoperative patients and should be further investigated as a potential therapeutic option
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