Multi‐Scale Model of O2 Transport and Metabolism

Regulation of pulmonary oxygen uptake (VO2p) during exercise depends on cellular energy demand, blood flow, ventilation, oxygen exchange across membranes, and oxygen utilization in the contracting skeletal muscle. In human and animal studies of metabolic processes that control cellular respiration in working skeletal muscle, pulmonary VO2 dynamics is measured at the mouth using indirect calorimetry. To provide information on the dynamic balance between oxygen delivery and oxygen consumption at the microvascular level, muscle oxygenation is measured using near-infrared spectroscopy. A multi-scale computational model that links O2 transport and cellular metabolism in the skeletal muscle was developed to relate the measurements and gain quantitative understanding of the regulation of VO2 at the cellular, tissue, and whole-body level. The model incorporates mechanisms of oxygen transport from the airway openings to the cell, as well as the phosphagenic and oxidative pathways of ATP synthesis in the muscle cells.