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.


A peculiar form of human locomotion – Speed-skating

Anthony Sargeant moved to the Netherlands in 1985 as Professor and Head of Department with a joint appointment in the University of Amsterdam and the Vrije University of Amsterdam. The passion for Speed skating was ubiquitous and he contributed some physiological insights into this research review which sought to describe the peculiar nature of this form of locomotion. Peculiar because paradoxically it crucially depends upon muscles not shortening doing work and generating muscle power but rather remaining in a fixed isometric contraction. It is the ability to sustain a low aerodynamic profile during the long glide element of the cycle which is the key to success. As the skater fatigues and can no longer maintain a low profile the body position rises and this leads to greater air-resistance and hence a slower speed in the long glide phase.
Journal of Sports Science
J Sports Sci. 1987 Winter;5(3):249-59

Speed skating exercise can be better understood by taking account of physiological and biomechanical considerations. Comparison with other sports shows the unique and peculiar way of skating propulsion. The relatively long lasting isometric muscle contractions during the gliding phase, alternated with high power output push-offs, place unusual demands on the (local) energy delivering systems.

The short and explosive push-off needs a specific pattern of motor unit recruitment. Some mixture of slow twitch (to sustain skating posture) and fast twitch fibres (to effect push off) in the hip and knee extensors seems necessary for optimal skating performance.

Fatigue in 10 second sprints and human muscle fibre type

This research was carried out by the talented Christina Karatzaferi as part of her PhD under the direction of Tony Sargeant. Utilizing techniques developed in his laboratory fragments of human muscle fibres were micro-dissected from samples obtained using the needle biopsy technique immediately after a 10 second sprint. Separated fragments were then classified according to fibre type. The level of high energy phosphate was measured in each fibre type and compared to the levels before exercise. This study is part of a long series concerned with anaerobic power and fatigue in human muscle starting with the paper published in 1981 (Sargeant, Hoinville and Young 1981 – note: although not written up until 1981 the work for this paper was actually conducted in the mid 1970s when Tony was working for the Medical Research Council).
Experimental Physiology
Exp Physiol. 2001 May;86(3):411-5


Changes in high-energy phosphate levels in single human skeletal muscle fibres after 10 s of maximal (all-out) dynamic exercise were investigated. Muscle biopsies from vastus lateralis of two volunteers were collected at rest and immediately post exercise. Single muscle fibres were dissected from dry muscle and were assigned into one of four groups according to their myosin heavy chain (MyHC) isoform content: that is type I, IIA, IIAx and IIXa (the latter two groups containing either less or more than 50% IIX MyHC).

Fragments of characterised fibres were analysed by HPLC for ATP, inosine-monophosphate (IMP), phosphocreatine (PCr) and creatine levels. After 10 s of exercise, PCr content ([PCr]) declined by approximately 46, 53, 62 and 59 % in type I, IIA, IIAx and IIXa fibres, respectively (P < 0.01 from rest). [ATP] declined only in type II fibres, especially in IIAx and IIXa fibres in which [IMP] reached mean values of 16 +/- 1 and 18 +/- 4 mmol (kg dry mass)(-1), respectively. While [PCr] was reduced in all fibre types during the brief maximal dynamic exercise, it was apparent that type II fibres expressing the IIX myosin heavy chain isoform were under a greatest metabolic stress as indicated by the reductions in [ATP].

Fatigue in sprint cycling exercise due to type II muscle fibres

This important study shows how depletion of the energy source for sprint exercise is depleted and remains depleted after a bout of sprint exercise lasting for 25 seconds. The study was part of the PhD work of the talented Christina Karatzaferi working under the direction of Professor Tony Sargeant.
Pflugers Archiv
Pflugers Arch. 2001 Jun;442(3):467-74

The recovery of high-energy phosphate levels in single human skeletal muscle fibres following short-term maximal (all-out) exercise was investigated. Three male volunteers exercised maximally for 25 s on an isokinetic cycling ergometer. Muscle biopsy samples from the vastus lateralis were collected at rest, immediately post-exercise and at 1.

5 min of recovery. The subjects also performed a second exercise bout 1.5 min after the first, on a separate occasion. Single muscle fibres were dissected, characterized and assigned to one of four groups according to their myosin heavy chain (MyHC) isoform content; namely, type I, IIA, IIAx and IIXa (the latter two groups containing either less or more than 50% IIX MyHC). Fibres were analysed for adenosine 5′-triphosphate (ATP), inosine-5′-monophosphate (IMP), phosphocreatine (PCr) and creatine (Cr) levels. Type I fibres had a lower Cr content than type II fibres (P<0.01). Within type II fibres resting [PCr] increased with increasing MyHC IIX isoform content (r=0.59, P<0.01). Post-exercise [PCr] was very low in all fibre groups (P<0.01 versus rest) while great reductions in ATP were also observed (P<0.01 versus rest), especially in the type II fibre groups. [PCr] at 1.5 min of recovery was still lower compared to rest for all fibre groups (P<0.01) especially in the IIAx and IIXa fibres.