The role of the microcirculation in skeletal muscle function and plasticity

Hendrickse, Paul William (2020) The role of the microcirculation in skeletal muscle function and plasticity. Doctoral thesis (PhD), Manchester Metropolitan University in Collaboration with the Lithuanian Sports University.

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Abstract

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.