Abstract
Oxygen and other substrates, waste products, hormone messengers, and cells and other particles of the immune system are all transported in a closed-loop circulatory system in vertebrates, within which pumped blood travels to within diffusion distances of practically every cell in the body. Exchange of oxygen and carbon dioxide in the pulmonary capillaries and absorption of nutrients in the gut provide the circulating blood with biochemical reactants to sustain bioenergetic processes throughout the body. Inputs and outputs transported by the microcirculation are necessary to drive the open-system nonequilibrium chemical reactions of metabolism that are essential for cellular function. In turn, metabolically derived signals influence microcirculatory dynamics. Indeed, the microcirculation is the key system that ties processes at the whole-body level of the cardiovascular system to subcellular phenomena. This tight integration between cellular metabolism and microcirculatory transport begs for integrative simulations that span the cell, tissue, and organ scales.