Relating pulmonary oxygen uptake to muscle oxygen consumption at exercise onset: in vivo and in silico studies

Assessment of the rate of muscle oxygen consumption, UO_2m, in vivo during exercise involving a large muscle mass is critical for investigating mechanisms regulating energy metabolism at exercise onset. While UO_2m is technically difficult to obtain under these circumstances, pulmonary oxygen uptake, VO_2p, can be readily measured and used as a proxy to UO_2m. However, the quantitative relationship between VO_2p and UO_2m during the nonsteady phase of exercise in humans, needs to be established. A computational model of oxygen transport and utilization—based on dynamic mass balances in blood and tissue cells—was applied to quantify the dynamic relationship between model-simulated UO_2m and measured VO_2p during moderate (M), heavy (H), and very heavy (V) intensity exercise. In seven human subjects, VO_2p and muscle oxygen saturation, StO_2m, were measured with indirect calorimetry and near infrared spectroscopy (NIRS), respectively. The dynamic responses of VO_2p and StO_2m at each intensity were in agreement with previously published data. The response time of muscle oxygen consumption, \(\tau_{{\rm UO}_{{2{\rm m}}}},\) estimated by direct comparison between model results and measurements of StO_2m was significantly faster (P < 0.001) than that of pulmonary oxygen uptake, \(\tau_{{\rm VO}_{{2{\rm p}}}},\) (M: 13 ± 4 vs. 65 ± 7 s; H: 13 ± 4 vs. 100 ± 24 s; V: 15 ± 5 vs. 82 ± 31 s). Thus, by taking into account the dynamics of oxygen stores in blood and tissue and determining muscle oxygen consumption from muscle oxygenation measurements, this study demonstrates a significant temporal dissociation between UO_2m and VO_2p at exercise onset.