A validated model of oxygen uptake and circulatory dynamic interactions at exercise onset in humans

At the onset of muscular exercise, the kinetics of pulmonary O2 uptake (Vo2P) reflect the integrated dynamic responses of the ventilatory, circulatory, and neuromuscular systems for O2 transport and utilization. Muscle O2 uptake (Vo2m) kinetics, however, are dissociated from Vo2P kinetics by intervening O2 capacitances and the dynamics of the circulation and ventilation. We developed a multicompartment computational model (MCM) to investigate these dynamic interactions and optimized and validated the MCM using previously published, simultaneously measured Vo2m, alveolar O2 uptake (Vo2A), and muscle blood flow (Qm) in healthy young men during cycle ergometry. The model was used to show that 1) the kinetics of Vo2A during exercise transients are very sensitive to preexercise blood flow distribution and the absolute value of Qm, 2) a low preexercise Qm exaggerates the magnitude of the transient fall in venous O2 concentration for any given Vo2m kinetics, necessitating a tighter coupling of Qm/Vo2m (or a reduction in the available work rate range) during the exercise transient to avoid limits to O2 extraction, and 3) information regarding exercise-related alterations in O2 uptake and blood flow in nonexercising tissues and their effects on mixed venous O2 concentration is required to accurately predict Vo2A kinetics from knowledge of Vo2m and Qm dynamics. Importantly, these data clearly demonstrate that Vo2A kinetics are nonexponential, nonlinear distortions of Vo2m kinetics that can be explained in a MCM by interactions among circulatory and cellular respiratory control processes before and during exercise.