The influence of metabolic and circulatory heterogeneity on the expression of pulmonary oxygen uptake kinetics in humans

New Findings What is the central question of this study? The finding that pulmonary oxygen uptake ( ) kinetics on transition to moderate exercise is invariant and exponential is consistent with a first‐order reaction controlling . However, slowed kinetics when initiating exercise from raised baseline intensities challenges this notion. What is the main finding and its importance? Here, we demonstrate how a first‐order system can respond with non‐first‐order response dynamics. Data suggest that progressive recruitment of muscle fibre populations having progressively lower mitochondrial density and slower microvascular blood flow kinetics can unify the seemingly contradictory evidence for the control of on transition to exercise. We examined the relationship amongst baseline work rate (WR), phase II pulmonary oxygen uptake ( ) time constant ( ) and functional gain during moderate‐intensity exercise. Transitions were initiated from a constant or variable baseline WR. A validated circulatory model was used to examine the role of heterogeneity in muscle metabolism ( ) and blood flow ( ) in determining kinetics. We hypothesized that and G P would be invariant in the constant baseline condition but would increase linearly with increased baseline WR. Fourteen men completed three to five repetitions of ∆40 W step transitions initiated from 20, 40, 60, 80, 100 and 120 W on a cycle ergometer. The ∆40 W step transitions from 60, 80, 100 and 120 W were preceded by 6 min of 20 W cycling, from which the progressive ΔWR transitions (constant baseline condition) were examined. The was measured breath by breath using mass spectrometry and a volume turbine. For a given ΔWR, both (22–35 s) and G P (8.7–10.5 ml min −1 W −1 ) increased ( P < 0.05) linearly as a function of baseline WR (20–120 W). The was invariant ( P < 0.05) in transitions initiated from 20 W, but G P increased with ΔWR ( P < 0.05). Modelling the summed influence of multiple muscle compartments revealed that could appear fast (24 s), and similar to in vivo measurements (22 ± 6 s), despite being derived from values with a range of 15–40 s and with a range of 20–45 s, suggesting that within the moderate‐intensity domain phase II kinetics are slowed dependent on the pretransition WR and are strongly influenced by muscle metabolic and circulatory heterogeneity.