The importance of capillary distribution in supporting muscle function, building on Krogh's seminal ideas

Krogh's Nobel prize for insightful studies into the physiology of capillaries heralded a revolution in understanding that continues today. The view of passive conduits has been replaced by capillaries recognised as a key element in haemodynamic control, offering both a site where changes in tissue demand are sensed and a driver of integrated vascular responses. In addition, the capillary bed is known to play an important role in metabolic, hormonal and immune homeostasis. Not surprisingly, therefore, microvascular dysfunction is a hallmark of many central and peripheral diseases, leading to widespread morbidity and mortality. Consequently, there is growing interest in how best to specifically target this organ-system by means of effective angiotherapies. Underpinning a lot of our current understanding of capillary physiology has been a recognition of functional heterogeneity among different microvascular beds. In addition, there is increasing awareness of the role that spatial heterogeneity plays in determining both physiological and pathological outcomes that has led to an appreciation that quality, rather than just quantity of microvascular supply is important. This has required a re-appraisal of the methods used to determine both the extent and topology of the capillary network, with the benefit of facilitating new ways of exploring dynamic regulation of capillary supply and its potential consequences. •Krogh recognised the variety of capillary content among tissue, and spatial variation was matched with temporal variation in perfusion.•Thus, he replaced the concept of passive capillary conduits with active components of haemodynamic control.•In particular, he devised a method to quantify the impact of capillary supply on O2 diffusion in muscle.•Krogh’s cylinder has been widely adopted in calculations of peripheral tissue oxygenation, despite a number of evident limitations.•Recent developments use accurate representation of capillary distribution and fibre type composition to better describe PO2 distribution in skeletal muscle.