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

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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

Summary

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.

Introduction

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.

http://www.clinsci.org/content/ppclinsci/52/4/337.full.pdf

Massive atrophy of leg muscle after being immobilized in plaster casts following fracture

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In this first published research on human muscle atrophy consequent upon immobilization in plaster casts Professor Anthony J Sargeant demonstrated that gross anthropometric measurement of leg muscle size vastly underestimated the magnitude of the reduction in cross sectional area of the muscle fibres themselves. Needle biopsies of the quadriceps muscle in young military personnel who had simple leg fractures and had been immobilized in plaster casts for between 6-12 weeks showed that the muscle fibres were reduced by nearly 50% in cross sectional area. This reduction would lead to a concomitant reduction in the maximum force that the muscle could generate.Furthermore the study indicated that even with intensive residential rehabilitation the rebuilding of muscle fibre size was a very slow process. Indeed subsequent studies and observations suggest that full recovery of muscle fibre size may never be recovered in the injured legs in many people suffering leg injury and consequent immobilization. It appears that the time course of muscle loss and muscle gain is asymmetric with loss of muscle occurring rapidly, within days of immobilization, while recovery of muscle size takes many weeks.
Clinical Science and Molecular Medicine
Clin Sci Mol Med. 1977 Apr;52(4):337-42

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 +/- 1-05 litres) compared with the uninjured (6-43 +/- 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 +/- 0-21 1/min in the uninjured leg to 1-57 +/- 0-18 1/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 II fibres were affected, being reduced respectively from 3410 to 1840 micronm2 and from 3810 to 2390 micronm2 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).

Dramatic loss of human muscle fibre size after leg fracture and immobilization in plaster casts

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Initiated and written by Professor Anthony J Sargeant while working at the Joint Services Medical Rehabilitation Centre at Chessington, Surrey, UK this was the first research paper in the scientific literature that showed the massive loss in muscle fibre size in otherwise healthy young male patients who following leg fracture had been immobilized in plaster casts. Although gross measurement of leg muscle size suggested a modest loss of about 12% after an average of 6 weeks in plaster cast needle biopsy of the vastus lateralis muscle revealed a reduction in cross sectional area of muscle fibres of nearly 50%. Furthermore recovery appeared very slow and many subjects seemed never to fully recover in terms of muscle fibre size and strength – deficits being identified in later studies many years later after the injury.
Clinical Science and Molecular Medicine
Clin Sci Mol Med. 1977 Apr;52(4):337-42

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 +/- 1-05 litres) compared with the uninjured (6-43 +/- 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 +/- 0-21 1/min in the uninjured leg to 1-57 +/- 0-18 1/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 II fibres were affected, being reduced respectively from 3410 to 1840 micronm2 and from 3810 to 2390 micronm2 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).

http://www.pubfacts.com/author/Anthony+J+Sargeant