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Title: Fatigue and damage as a result of exercise in normal and diseased skeletal muscle
Author: Sacco, Paul
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1992
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This thesis examines the nature of fatigue and damage as it affects healthy and dystrophic skeletal muscle. Initial fatigue studies were carried out using isolated mouse muscles. After 3 min of repeated maximal stimulation, extensor digitorum longus muscle force was reduced to 26% of the fresh value but this could be reversed by the addition of caffeine to the incubation medium, suggesting that acute fatigue is primarily due to failure of the processes of activation. In the human tibialis anterior (TA) muscle it was found that fatigue resulting from stimulated isometric contractions were affected by muscle length. Exercise at short lengths resulted in less force loss at the resting length, whereas exercise at long muscle lengths caused a greater force loss than normal at the resting length. There was a preferential force loss at sub-maximal stimulation frequencies, and this was exacerbated when muscles were exercised in a lengthened positon. Similar changes were observed using isolated mouse soleus muscles. Because of uncertainties about the adequate diffusion of metabolites in isolated muscles the properties of dystrophin-deficient (mdx) mouse muscles were investigated using an in vivo preparation of the TA. The mdx TA was, on average, 30% stronger than that of control mice but had a reduced force/cross-sectional area and a smaller low/high frequency force ratio due to a faster activation time, mdx muscle also displayed a greater fatigue resistance when exercised at a low frequency, but this was not the case with stimulation at maximal frequency. In order to test whether the altered contractile properties of mdx muscle were due to the presence of degenerating and regenerating fibres, the contractile characteristics of normal muscle were investigated during damage and recovery. Damage was induced by stimulated lengthening 1 contractions of the foot dorsiflexor muscles of mice. Maximum force, force-frequency characteristics, and morphology were measured for up to 20 days after exercise. Although the properties of normal/damaged and mdx muscles displayed a number of superficial similarities, it is unlikely that the altered contractile characteristics of mdx muscles are due to the presence of damaged fibres. The possibility that dystrophin-deficient muscles are more susceptible to exercise induced muscle damage was examined by comparing the responses of mdx and muscles to an episode of eccentric work. The findings were unequivocal, normal and mdx TA muscles displayed similar degrees of force loss 3 days after exercise (55% and 52% respectively) and comparable rates of force recovery after 12 days (76% and 80% of control in normal and mdx muscles respectively). The protective effect afforded by a bout of eccentric exercise against subsequent muscle injury from a similar exercise was characterised. Re-exercising a muscle after 10 days recovery had little effect on the immediate consequences of exercise, but reduced the degree of delayed onset force loss and fibre necrosis. Animals re-exercised after 12 weeks recovery displayed no apparent protection against delayed onset muscle damage when the exercise was repeated. These findings me in general agreement with work carried out in humans, but the time course of recovery post exercise is at least three times faster in the mouse, which has made a study of the long-term effects of eccentric exercise more practical. Six weeks after exercise, increases in muscle mass and force were evident, with a proportion of fibres displaying internal nuclei and signs of fibre splitting. Surprisingly, greater forces and fibre hypertrophy also occurred after 12 weeks recovery from an episode of eccentric work.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available