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

Abstract

New Findings: What is the central question of this study? The finding that pulmonary oxygen uptake ((Formula presented.)o2p) kinetics on transition to moderate exercise is invariant and exponential is consistent with a first-order reaction controlling (Formula presented.)o2p. However, slowed (Formula presented.)o2p 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 (Formula presented.)o2p on transition to exercise. We examined the relationship amongst baseline work rate (WR), phase II pulmonary oxygen uptake ((Formula presented.)o2p) time constant (τ(Formula presented.)o2p) and functional gain (Gp=△(Formula presented.)o2p/△WR) 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 ((Formula presented.)o2m) and blood flow ((Formula presented.)m) in determining (Formula presented.)o2p kinetics. We hypothesized that τ(Formula presented.)o2p and GP 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 (Formula presented.)o2p was measured breath by breath using mass spectrometry and a volume turbine. For a given ΔWR, both τ(Formula presented.)o2p (22–35 s) and GP (8.7–10.5 ml min−1 W−1) increased (P < 0.05) linearly as a function of baseline WR (20–120 W). The τ(Formula presented.)o2p was invariant (P < 0.05) in transitions initiated from 20 W, but GP increased with ΔWR (P < 0.05). Modelling the summed influence of multiple muscle compartments revealed that τ(Formula presented.)o2p could appear fast (24 s), and similar to in vivo measurements (22 ± 6 s), despite being derived from τ(Formula presented.)o2p values with a range of 15–40 s and τ(Formula presented.)m with a range of 20–45 s, suggesting that within the moderate-intensity domain phase II (Formula presented.)o2p kinetics are slowed dependent on the pretransition WR and are strongly influenced by muscle metabolic and circulatory heterogeneity.