How cardiac output is regulated: August Krogh's proto-Guytonian understanding of the importance of venous return.

August Krogh pioneered a view of cardiac output that emphasised the rate of venous return, and stressed the importance of changing the filling of the 'inadequately' supplied heart, instead of changes in heart rate or cardiac inotropy. Krogh, by and large, presented this concept in three manuscripts published in 1912, which relied on innovative experimental techniques (developed in collaboration with Johannes Lindhard) as well as mathematical and physical models. In this graphical review, we revisit Krogh's original articles, demonstrate how they have stood the test of time, and show how they are relevant to comparative cardiovascular physiology. In doing so, we present an overview of the fundamental, but sometimes counterintuitive, principle that peripheral factors are at least as important as cardiac function in determining cardiac output.