Multiscale modeling of respiration.

In human studies investigating factors that control cellular respiration in working skeletal muscle, pulmonary VO dynamics (VO) measured at the mouth by indirect calorimetry is typically used to represent muscle O consumption (UO). Furthermore, measurement of muscle oxygenation using near-infrared spectroscopy has provided information on the dynamic balance between oxygen delivery and oxygen consumption at the microvascular level. To relate these measurements and gain quantitative understanding of the regulation of VO at the cellular, tissue and whole-body level, a multiscale computational model of oxygen transport and metabolism during exercise was developed. The model incorporates mechanisms of oxygen transport from the airway opening to working muscle and other-organs cells, as well as the phosphagenic and oxidative pathways of ATP synthesis in these tissue cells. Model simulations of external (VO) and cellular (UO) respiration show that, during moderate exercise, their characteristic mean response times are similar even when a transit delay exists between tissue cells and the external environment for normal subjects.