The skeletal muscle microcirculation is crucial for the delivery of oxygen and
nutrients, and the removal of waste products, but the importance of capillarisation
for skeletal muscle performance and hypertrophy is yet to be fully elucidated.
Therefore, the aim of the thesis was to assess, in rodents and humans, the role of
capillarisation in skeletal muscle fatigue resistance and hypertrophy in health,
disease (chronic heart failure (CHF) in particular) and ageing and to determine to
what extent baseline muscle mass affects the hypertrophic response.
Through the use of microsphere injection to block up to 70% of capillaries in the m.
extensor digitorum longus (EDL) it was shown that functional capillary density is
positively related to the fatigue resistance of a muscle. The reduction in fatigue
resistance as a consequence of unbiased blockage of capillaries can be overcome
by overload-induced angiogenesis, and in the case of the rats with compensatory
cardiac hypertrophy (a model for hypertension and early chronic heart failure (CHF))
by endurance exercise. CHF reduces functional capillary density in muscle and
impairs the hypertrophic response to overload. Given the inverse relationship
between fibre cross-sectional area (FCSA) and oxidative capacity, it was expected
that the FCSA of highly-resistance trained men would decrease as their oxidative
capacity increased with endurance training, with even greater reductions in FCSA
in old resistance-trained men. This was, however, not the case probably because
the endurance exercise-induced angiogenesis reduced intercapillary distances,
facilitating the oxygen delivery via diffusion to the increased number of mitochondria
in the muscle fibres. In mice it was seen that the inclusion of hypertrophic and
endurance stimuli did not blunt the adaptations to either modality and that baseline
muscle mass was not predictive of hypertrophic response in young mice. It was
shown, however that old mice demonstrated less hypertrophy, which was
associated with an impaired overload-induced angiogenesis.
In conclusion, the microcirculation plays a crucial role in skeletal muscle fatigue
resistance and is important in reducing diffusion distances with hypertrophy. As
such, it appears to be a useful therapeutic target to maintain muscle function and
enhance muscle responses to rehabilitation in disease and old age