We examined the relationship amongst baseline work rate (WR), phase II pulmonary oxygen uptake (V̇(O2p)) time constant (τV̇(O2p)) and functional gain (G(P)=ΔV̇(O2p)/ΔWR) 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 (V̇(O2m)) and blood flow (Q̇(m)) in determining V̇(O2p) kinetics. We hypothesized that τV̇(O2p) 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 V̇(O2p) was measured breath by breath using mass spectrometry and a volume turbine. For a given ΔWR, both τV̇(O2p) (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 τV̇(O2p) 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 τV̇(O2p) could appear fast (24 s), and similar to in vivo measurements (22 ± 6 s), despite being derived from τV̇(O2p) values with a range of 15-40 s and τQ̇(m) with a range of 20-45 s, suggesting that within the moderate-intensity domain phase II V̇(O2p) kinetics are slowed dependent on the pretransition WR and are strongly influenced by muscle metabolic and circulatory heterogeneity.

It remains unclear whether an overshoot in skeletal muscle deoxygenation (HHb; reflecting a microvascular kinetic mismatch of O2 delivery to consumption) contributes to the slowed adjustment of oxidative energy provision at the onset of exercise. We progressively reduced the fractional inspired O2 concentration (F(I,O2)) to investigate the relationship between slowed pulmonary O2 uptake (V(O2)) kinetics and the dynamics and spatial distribution of absolute[HHb]. Seven healthy men performed 8 min cycling transitions during normoxia (F(I,O2) = 0.21),moderate hypoxia (F(I,O2) = 0.16) and severe hypoxia (F(I,O2)= 0.12). V(O2) uptake was measured using a flowmeter and gas analyser system. Absolute [HHb] was quantified by multichannel,time-resolved near-infrared spectroscopy from the rectus femoris and vastus lateralis (proximal and distal regions), and corrected for adipose tissue thickness. The phase II V(O2) time constant was slowed (P <0.05) as F(I,O2) decreased (normoxia, 17 ± 3 s;moderate hypoxia, 22 ± 4 s; and severe hypoxia, 29 ± 9 s). The [HHb] overshoot was unaffected by hypoxia, but the transient peak [HHb] increased with the reduction in F(I,O2) (P <0.05). Slowed V(O2) kinetics in hypoxia were positively correlated with increased peak [HHb] in the transient (r(2) = 0.45; P <0.05), but poorly related to the [HHb] overshoot. A reduction of spatial heterogeneity in peak [HHb]was inversely correlated with slowed V(O2) kinetics (r(2) = 0.49; P <0.05). These data suggest that aerobic energy provision at the onset of exercise may be limited by the following factors: (i) the absolute ratio (i.e. peak [HHb]) rather than the kinetic ratio (i.e. [HHb] overshoot) of microvascular O2 delivery to consumption; and (ii) a reduced spatial distribution in the ratio of microvascular O2 delivery to consumption across the muscle.

Skeletal muscle deoxygenated hemoglobin and myoglobin concentration ([HHb]), assessed by near-infrared spectroscopy (NIRS), is commonly used as a surrogate of regional O2 extraction (reflecting the O2 delivery-to-consumption ratio, Q̇/V̇o2). However, [HHb] change (Δ[HHb]) is also influenced by capillary-venous heme concentration, and/or small blood vessel volume (reflected in total heme; [THb]). We tested the hypotheses that Δ[HHb] is associated with O2 extraction, and insensitive to [THb], over a wide range of Q̇/V̇o2 elicited by passive head-up tilt (HUT; 10-min, 15° increments, between -10° and 75°). Steady-state common femoral artery blood flow (FBF) was measured by echo-Doppler, and time-resolved NIRS measured [HHb] and [THb] of vastus lateralis (VL) and gastrocnemius (GS) in 13 men. EMG confirmed muscles were inactive. During HUT in VL [HHb] increased linearly (57 ± 10 to 101 ± 16 μM; P < 0.05 above 15°) and was associated (r(2) ∼ 0.80) with the reduction in FBF (618 ± 75 ml/min at 0° to 268 ± 52 ml/min at 75°; P < 0.05 above 30°) and the increase in [THb] (228 ± 30 vs. 252 ± 32 μM; P < 0.05 above 15°). GS response was qualitatively similar to VL. However, there was wide variation within and among individuals, such that the overall limits of agreement between Δ[HHb] and ΔFBF ranged from -35 to +19% across both muscles. Neither knowledge of tissue O2 saturation nor vascular compliance could appropriately account for the Δ[HHb]-ΔFBF dissociation. Thus, under passive tilt, [HHb] is influenced by Q̇/V̇o2, as well as microvascular hematocrit and/or tissue blood vessel volume, complicating its use as a noninvasive surrogate for muscle microvascular O2 extraction.

The pulmonary O2 uptake (V̇o2p) response to ramp-incremental (RI) exercise increases linearly with work rate (WR) after an early exponential phase, implying that a single time constant (τ) and gain (G) describe the response. However, variability in τ and G of V̇o2p kinetics to different step increments in WR is documented. We hypothesized that the "linear" V̇o2p-WR relationship during RI exercise results from the conflation between WR-dependent changes in τ and G. Nine men performed three or four repeats of RI exercise (30 W/min) and two step-incremental protocols consisting of four 60-W increments beginning from 20 W or 50 W. During testing, breath-by-breath V̇o2p was measured by mass spectrometry and volume turbine. For each individual, the V̇o2p RI response was characterized with exponential functions containing either constant or variable τ and G values. A relationship between τ and G vs. WR was determined from the step-incremental protocols to derive the variable model parameters. τ and G increased from 21 ± 5 to 98 ± 20 s and from 8.7 ± 0.6 to 12.0 ± 1.9 ml·min(-1)·W(-1) for WRs of 20-230 W, respectively, and were best described by a second-order (τ) and a first-order (G) polynomial function of WR (lowest Akaike information criterion score). The sum of squared residuals was not different (P > 0.05) when the V̇o2p RI response was characterized with either the constant or variable models, indicating that they described the response equally well. Results suggest that τ and G increase progressively with WR during RI exercise. Importantly, these relationships may conflate to produce a linear V̇o2p-WR response, emphasizing the influence of metabolic heterogeneity in determining the apparent V̇o2p-WR relationship during RI exercise.

Oxygen uptake kinetics (τVO2) are slowed when exercise is initiated from a raised metabolic rate. Whether this reflects the recruitment of muscle fibres differing in oxidative capacity, or slowed blood flow (Q) kinetics is unclear. This study determined τVO2 in canine muscle in situ, with experimental control over muscle activation and Q during contractions initiated from rest and a raised metabolic rate. The gastrocnemius complex of nine anaesthetised, ventilated dogs was isolated and attached to a force transducer. Isometric tetanic contractions (50 Hz; 200 ms duration) via supramaximal sciatic nerve stimulation were used to manipulate metabolic rate: 3 min stimulation at 0.33 Hz (S1), followed by 3 min at 0.67 Hz (S2). Circulation was initially intact (SPON), and subsequently isolated for pump-perfusion (PUMP) above the greatest value in SPON. Muscle VO2 was determined contraction-by-contraction using an ultrasonic flowmeter and venous oximeter, and normalised to tension-time integral (TTI). τVO2/TTI and τQ were less in S1SPON (mean ± s.d.: 13 ± 3 s and 12 ± 4 s, respectively) than in S2SPON (29 ± 19 s and 31 ± 13 s, respectively; P < 0.05). τVO2/TTI was unchanged by pump-perfusion (S1PUMP, 12 ± 4 s; S2PUMP, 24 ± 6 s; P < 0.001) despite increased O2 delivery; at S2 onset, venous O2 saturation was 21 ± 4% and 65 ± 5% in SPON and PUMP, respectively. VO2 kinetics remained slowed when contractions were initiated from a raised metabolic rate despite uniform muscle stimulation and increased O2 delivery. The intracellular mechanism may relate to a falling energy state, approaching saturating ADP concentration, and/or slowed mitochondrial activation; but further study is required. These data add to the evidence that muscle VO2 control is more complex than previously suggested.