August Krogh: Muscle capillary function and oxygen delivery.

The capillary bed constitutes the obligatory pathway for almost all oxygen (O2) and substrate molecules as they pass from blood to individual cells. As the largest organ, by mass, skeletal muscle contains a prodigious surface area of capillaries that have a critical role in metabolic homeostasis and must support energetic requirements that increase as much as 100-fold from rest to maximal exercise. In 1919 Krogh's 3 papers, published in the Journal of Physiology, brilliantly conflated measurements of muscle capillary function at rest and during contractions with Agner K. Erlang's mathematical model of O2 diffusion. These papers single-handedly changed the perception of capillaries from passive vessels serving at the mercy of their upstream arterioles into actively contracting vessels that were recruited during exercise to elevate blood-myocyte O2 flux. Although seminal features of Krogh's model have not withstood the test of time and subsequent technological developments, Krogh is credited with helping found the field of muscle microcirculation and appreciating the role of the capillary bed and muscle O2 diffusing capacity in facilitating blood-myocyte O2 flux. Today, thanks in large part to Krogh, it is recognized that comprehending the role of the microcirculation, as it supports perfusive and diffusive O2 conductances, is fundamental to understanding skeletal muscle plasticity with exercise training and resolving the mechanistic bases by which major pathologies including heart failure and diabetes cripple exercise tolerance and cerebrovascular dysfunction predicates impaired executive function.