Functional and structural changes after disuse of human muscle – first study to quantify disuse muscle atrophy at fibre level in humans


Clinical Science and Molecular Medicine (1977) 52, 337-342. Functional and structural changes after disuse of human muscle – Authors: ANTHONY J SARGEANT,* C. T. M. DAVIES,* R. H. T. EDWARDS, C. MAUNDER AND A. YOUNG *Medical Research Council Environmental Physiology Unit, London School of Hygiene and Tropical Medicine, University of London, and Jerry Lewis Muscle Research Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London


1. Seven patients who had suffered unilateral leg fracture were studied after removal of immobilizing plaster casts.

2. Leg volume measured anthropometrically was reduced by 12% in the injured leg (5.68 f 1.05 litres) compared with the uninjured (6.43 f 0.87 litres). Associated with this loss was a similar reduction in the net maximum oxygen uptake achieved in one-leg cycling, from 1.89 k 0.21 l/min in the uninjured leg to 1.57+0.18 l/min in the injured.

3. Measured by a percutaneous needle biopsy technique, a reduction of 42% was found in the cross-sectional area of the muscle fibres sampled from the vastus lateralis of the injured compared with the uninjured leg.

4. Staining for myosin adenosine triphosphatase activity showed that both type I and I1 fibres were affected, being reduced respectively from 3410 to 1840 pm2 and from 3810 to 2390 pm2 cross-sectional area.

5. Possible reasons and implications are discussed for the discrepancy between the magnitude of the difference observed in the gross measurement of leg function (maximum oxygen uptake) and structure (leg volume) as compared with the cellular level (cross-sectional fibre area).


Correspondence: Dr A. J. Sargeant, MRC Environmental Physiology Unit, London School of Hygiene and Tropical Medicine, University of London, Keppel Street (Gower Street), London WClE 7HT.


Atrophy of the affected limb and loss of muscle power follows bone fracture and subsequent immobilization. Years of experience have enabled the rehabilitation professions to develop empirical programmes to reverse these changes. However, the efficacy of such programmes may be further improved if we can increase our understanding of the atrophic response to disuse in human muscle. Recent studies showed that 15 weeks immobilization in a long-leg plaster cast after fracture reduced the fat-free volume of the affected leg by 12%, which was accompanied by a similar fall in the maximum oxygen uptake ( ~oz,,,,=.) achieved with oneleg pedalling (Davies & Sargeant, 1975a,b). However, it was not known how far these changes in gross structure and function were reflected at a cellular level within the affected muscles. Since the work of pedalling is performed mainly by the leg extensors (A. J. Sargeant & C. T. M. Davies, unpublished work) needle biopsy was used (Edwards, Maunder, Lewis & Pearse, 1973) to study fibre atrophy in the quadriceps femoris muscle and to compare this with measurements of the gross leg volume and maximal oxygen uptake of patients recovering from unilateral leg fracture.

Skeletal muscle in renal patients shows atrophy and reduced capillarization

Nephrology Dialysis and Transplantation
Nephrol Dial Transplant. 2003 Oct;18(10):2074-81


BACKGROUND: All previous histological studies of skeletal muscles of patients with renal failure have used locomotor muscle biopsies. It is thus unclear to what degree the observed abnormalities are due to the uraemic state and how much is due to disuse. The present study was undertaken to attempt to investigate this question by examining a non-locomotor muscle (rectus abdominis) in patients with end-stage renal failure.


METHODS: Biopsies from rectus abdominis were obtained from 22 renal failure patients (RFPs) undergoing surgical Tenchkoff catheter implantation for peritoneal dialysis and 20 control subjects undergoing elective abdominal surgery. Histochemical staining of frozen sections and morphometric analysis was used to estimate the proportion of each fibre type, muscle fibre area and capillary density. Myosin heavy chain composition was examined by SDS-PAGE.

RESULTS: There were no differences in fibre type distribution between RFPs and controls. All RFPs showed fibre atrophy [mean cross-sectional area (CSA) 3300 +/- 1100 microm2, compared to 4100 +/- 1100 microm2 in controls (P < 0.05)]. All fibre types were smaller in mean CSA in RFPs than in controls (15, 26 and 28% for types I, IIa and IIx, respectively). These differences could not be accounted for by differences in age, gender or cardiovascular or diabetic comorbidity. Muscle fibre capillarization, expressed as capillaries per fibre or capillary contacts per fibre, was significantly less in RFPs.

CONCLUSIONS: Since a non-locomotor muscle was examined, the effects of disuse as a cause of atrophy have been minimized. It is likely, therefore, that the decreased muscle fibre CSA and capillary density of RFPs compared to controls were due predominantly to uraemia itself.