The effect of increasing work rate amplitudes from a common metabolic baseline on the kinetic response of V̇o2p, blood flow, and muscle deoxygenation.

A step-transition in external work rate (WR) increases pulmonary O2 uptake (V̇o2p) in a monoexponential fashion. Although the rate of this increase, quantified by the time constant (τ), has frequently been shown to be similar between multiple different WR amplitudes (ΔWR), the adjustment of O2 delivery to the muscle (via blood flow; BF), a potential regulator of V̇o2p kinetics, has not been extensively studied. To investigate the role of BF on V̇o2p kinetics, 10 participants performed step-transitions on a knee-extension ergometer from a common baseline WR (3 W) to: 24, 33, 45, 54, and 66 W. Each transition lasted 8 min and was repeated four to six times. Volume turbinometry and mass spectrometry, Doppler ultrasound, and near-infrared spectroscopy were used to measure V̇o2p, BF, and muscle deoxygenation (deoxy[Hb + Mb]), respectively. Similar transitions were ensemble-averaged, and phase II V̇o2p, BF, and deoxy[Hb + Mb] were fit with a monoexponential nonlinear least squares regression equation. With increasing ΔWR, τV̇o2p became larger at the higher ΔWRs (P < 0.05), while τBF did not change significantly, and the mean response time (MRT) of deoxy[Hb + Mb] became smaller. These findings that V̇o2p kinetics become slower with increasing ΔWR, while BF kinetics are not influenced by ΔWR, suggest that O2 delivery could not limit V̇o2p in this situation. However, the speeding of deoxy[Hb + Mb] kinetics with increasing ΔWR does imply that the O2 delivery-to-O2 utilization of the microvasculature decreases at higher ΔWRs. This suggests that the contribution of O2 delivery and O2 extraction to V̇O2 in the muscle changes with increasing ΔWR.NEW & NOTEWORTHY A step increase in work rate produces a monoexponential increase in V̇o2p and blood flow to a new steady-state. We found that step transitions from a common metabolic baseline to increasing work rate amplitudes produced a slowing of V̇o2p kinetics, no change in blood flow kinetics, and a speeding of muscle deoxygenation kinetics. As work rate amplitude increased, the ratio of blood flow to V̇o2p became smaller, while the amplitude of muscle deoxygenation became greater. The gain in vascular conductance became smaller, while kinetics tended to become slower at higher work rate amplitudes.

Data analysis technique influences blood flow kinetics parameter estimates for moderate- and heavy-intensity exercise transitions.

NEW FINDINGS: What is the central question of this study? During exercise, there are fluctuations in conduit artery blood flow (BF) caused by both cardiac and muscle contraction-relaxation cycles. What is the optimal method to process Doppler ultrasound-measured BF for the purpose of characterizing the dynamic response of BF during step-transitions in exercise? What is the main finding and its importance? Continuous BF data were processed in relation to either cardiac or muscle contraction-relaxation cycles and computed based on 'binned' or 'rolling' averages over one, two or five consecutive cycles. Kinetics characterization revealed no data processing technique-specific differences in steady-state BF, but variability in the rapidity at which BF attained steady-state (i.e., mean response time) was observed. ABSTRACT: The overall rate of blood flow (BF) adjustment (i.e., kinetics) from the onset of an exercise transition can be quantified by the mean response time (MRT). However, the BF response profile can be distorted during rhythmic, dynamic exercise consequent to variations caused by the cardiac cycle (HR) and the muscle contraction-relaxation (CR) cycle. We examined the extent to which distortions imposed by HR and CR cycles affected BF kinetics. Eight healthy, young men (27 (4) years; mean (SD)) performed transitions of alternate-leg knee-extension exercise from 3 W to either a moderate- (MOD) or heavy-intensity (HVY) power output. Femoral artery BF was continuously measured by Doppler ultrasound and averaged over one, two or five 'binned' (e.g., HR2b, etc.) or 'rolling' (e.g., CR5r, etc.) HR and CR cycles. Among analysis techniques, there were no differences for steady-state BF values at the 3 W baseline. In MOD, MRT using contraction-relaxation cycle (CR1) was smaller than most other analysis techniques. For both MOD and HVY, the 95% confidence interval for MRT was generally larger when using HR- compared to CR-related methods, and monoexponential fits based on 'rolling' averages (HR2r, HR5r, CR2r, CR5r) had a poorer ability to estimate the true end-exercise BF in HVY than in MOD. When modelling BF kinetics, we conclude that the CR1 method is a good option because of its ability to accurately estimate the 'data-determined' end-exercise BF value from the 'model-derived' response, maintain a relatively high density of data points during the transition and yield a relatively small 95% CI.

Effect of heavy-intensity 'priming' exercise on oxygen uptake and muscle deoxygenation kinetics during moderate-intensity step-transitions initiated from an elevated work rate.

We examined the effect of heavy-intensity 'priming' exercise on the rate of adjustment of pulmonary O2 uptake (τV˙O2p) initiated from elevated intensities. Fourteen men (separated into two groups: τV˙O2p≤25s [Fast] or τV˙O2p>25s [Slow]) completed step-transitions from 20W to 45% lactate threshold (LT; lower-step, LS) and 45% to 90%LT (upper-step, US) performed (i) without; and (ii) with US preceded by heavy-intensity exercise (HUS). Breath-by-breath V˙O2p and near-infrared spectroscopy-derived muscle deoxygenation ([HHb+Mb]) were measured. Compared to LS, τV˙O2p was greater (p<0.05) in US in both Fast (LS, 19±4s; US, 30±4s) and Slow (LS, 25±5s; US, 40±11s) with τV˙O2p in US being lower (p<0.05) in Fast. In HUS, τV˙O2p in Slow was reduced (28±8s, p<0.05) and was not different (p>0.05) from LS or Fast group US. In Slow, τ[HHb+Mb] increased (p<0.05) in US relative to HUS; this finding coupled with a reduced τV˙O2p indicates a priming-induced improvement in matching of muscle O2 delivery-to-O2 utilization during transitions from elevated intensities in those with Slow but not Fast V˙O2p kinetics.

Influence of muscle metabolic heterogeneity in determining the V̇o2p kinetic response to ramp-incremental exercise.

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.

The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity.

Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity (r(2) = 0.399, P = 0.001) and PDP1 protein expression (r(2) = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1α (r(2) = 0.310, P = 0.002) and PDK2 protein (r(2) = 0.229, P =0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ∼ 18% of the variance in PDP activity (r(2) = 0.184, P = 0.033). In addition, PDP1 in combination with E1α explained ∼ 38% of the variance in PDP activity (r(2) = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1α), in concert with higher potential for PDH activation (PDP activity).