Daryl P. Wilkerson

Acute dietary nitrate supplementation improves cycling time trial performance.

PURPOSE Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance. However, it is presently unknown whether it may enhance performance during simulated competition. The present study investigated the effects of acute dietary nitrate supplementation on power output (PO), VO2, and performance during 4- and 16.1-km cycling time trials (TT). METHODS After familiarization, nine club-level competitive male cyclists were assigned in a randomized, crossover design to consume 0.5 L of beetroot juice (BR; containing ∼ 6.2 mmol of nitrate) or 0.5 L of nitrate-depleted BR (placebo, PL; containing ∼ 0.0047 mmol of nitrate), ∼ 2.5 h before the completion of a 4- and a 16.1-km TT. RESULTS BR supplementation elevated plasma [nitrite] (PL = 241 ± 125 vs BR = 575 ± 199 nM, P < 0.05). The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance (P > 0.05), but BR significantly increased mean PO during the 4-km (PL = 279 ± 51 vs BR = 292 ± 44 W, P < 0.05) and 16.1-km TT (PL = 233 ± 43 vs BR = 247 ± 44 W, P < 0.01). Consequently, BR improved 4-km performance by 2.8% (PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min, P < 0.05) and 16.1-km performance by 2.7% (PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min, P < 0.01). CONCLUSIONS These results suggest that acute dietary nitrate supplementation with 0.5 L of BR improves cycling economy, as demonstrated by a higher PO for the same VO2 and enhances both 4- and 16.1-km cycling TT performance.

Muscular and pulmonary O2 uptake kinetics during moderate‐ and high‐intensity sub‐maximal knee‐extensor exercise in humans

The purpose of this investigation was to determine the contribution of muscle O2 consumption () to pulmonary O2 uptake () during both low‐intensity (LI) and high‐intensity (HI) knee‐extension exercise, and during subsequent recovery, in humans. Seven healthy male subjects (age 20–25 years) completed a series of LI and HI square‐wave exercise tests in which (direct Fick technique) and (indirect calorimetry) were measured simultaneously. The mean blood transit time from the muscle capillaries to the lung (MTTc‐l) was also estimated (based on measured blood transit times from femoral artery to vein and vein to artery). The kinetics of and were modelled using non‐linear regression. The time constant (τ) describing the phase II kinetics following the onset of exercise was not significantly different from the mean response time (initial time delay +τ) for kinetics for LI (30 ± 3 vs 30 ± 3 s) but was slightly higher (P < 0.05) for HI (32 ± 3 vs 29 ± 4 s); the responses were closely correlated (r= 0.95 and r= 0.95; P < 0.01) for both intensities. In recovery, agreement between the responses was more limited both for LI (36 ± 4 vs 18 ± 4 s, P < 0.05; r=−0.01) and HI (33 ± 3 vs 27 ± 3 s, P > 0.05; r=−0.40). MTTc‐l was ∼17 s just before exercise and decreased to 12 and 10 s after 5 s of exercise for LI and HI, respectively. These data indicate that the phase II kinetics reflect kinetics during exercise but not during recovery where caution in data interpretation is advised. Increased probably makes a small contribution to during the first 15–20 s of exercise.

Prior heavy exercise enhances performance during subsequent perimaximal exercise

PURPOSE To test the hypothesis that prior heavy exercise increases the time to exhaustion during subsequent perimaximal exercise. METHODS Seven healthy males (mean +/- SD 27 +/- 3 yr; 78.4 +/- 0.7 kg) completed square-wave transitions from unloaded cycling to work rates equivalent to 100, 110, and 120% of the work rate at VO2peak (W-[VO2peak) after no prior exercise (control, C) and 10 min after a 6-min bout of heavy exercise at 50% Delta (HE; half-way between the gas exchange threshold (GET) and VO2peak), in a counterbalanced design. RESULTS Blood [lactate] was significantly elevated before the onset of the perimaximal exercise bouts after prior HE (approximately 2.5 vs approximately 1.1 mM; P < 0.05). Prior HE increased time to exhaustion at 100% (mean +/- SEM. C: 386 +/- 92 vs HE: 613 +/- 161 s), 110% (C: 218 +/- 26 vs HE: 284 +/- 47 s), and 120% (C: 139 +/- 18 vs HE: 180 +/- 29 s) of W-VO2peak, (all P < 0.01). VO2 was significantly higher at 1 min into exercise after prior HE at 110% W-VO2peak (C: 3.11 +/- 0.14 vs HE: 3.42 +/- 0.16 L x min(-1); P < 0.05), and at 1 min into exercise (C: 3.25 +/- 0.12 vs HE: 3.67 +/- 0.15; P < 0.01) and at exhaustion (C: 3.60 +/- 0.08 vs HE: 3.95 +/- 0.12 L x min(-1); P < 0.01) at 120% of W-VO2peak. CONCLUSIONS This study demonstrate that prior HE, which caused a significant elevation of blood [lactate], resulted in an increased time to exhaustion during subsequent perimaximal exercise presumably by enabling a greater aerobic contribution to the energy requirement of exercise.

Inhibition of Nitric Oxide Synthase by L‐NAME Speeds Phase II Pulmonary V̇O2 Kinetics in the Transition to Moderate‐Intensity Exercise in Man

There is evidence that the rate at which oxygen uptake (V̇O2) rises at the transition to higher metabolic rates within the moderate exercise intensity domain is modulated by oxidative enzyme inertia, and also that nitric oxide regulates mitochondrial function through competitive inhibition of cytochrome c oxidase in the electron transport chain. We therefore hypothesised that inhibition of nitric oxide synthase (NOS) by nitro‐L‐arginine methyl ester (L‐NAME) would alleviate the inhibition of mitochondrial V̇O2 by nitric oxide and result in a speeding of V̇O2 kinetics at the onset of moderate‐intensity exercise. Seven males performed square‐wave transitions from unloaded cycling to a work rate requiring 90 % of predetermined gas exchange threshold with and without prior intravenous infusion of L‐NAME (4 mg kg−1 in 50 ml saline over 60 min). Pulmonary gas exchange was measured breath‐by‐breath and V̇O2 kinetics were determined from the averaged response to four exercise bouts performed in each condition using a mono‐exponential function following elimination of the phase I response. There were no significant differences between the control and L‐NAME conditions for baseline V̇O2 (means ±s.e.m. 797 ± 32 vs. 794 ± 29), the duration of phase I (15.4 ± 0.8 vs. 17.2 ± 0.6), or the steady‐state increment in V̇O2 above baseline (1000 ± 83 vs. 990 ± 85 ml min−1), respectively. However, the phase II time constant of the V̇O2 response was significantly smaller following L‐NAME infusion (22.1 ± 2.4 vs. 17.9 ± 2.3; P < 0.05). These data indicate that inhibition of NOS by L‐NAME results in a significant (19 %) speeding of pulmonary V̇O2 kinetics in the transition to moderate‐intensity cycle exercise in man. At least part of the intrinsic inertia to oxidative metabolism at the onset of moderate‐intensity exercise may result from competitive inhibition of mitochondrial V̇O2 by nitric oxide at cytochrome c oxidase, although other mechanisms for the effect of L‐NAME on V̇O2 kinetics remain to be explored.

Optimizing the "priming" effect: influence of prior exercise intensity and recovery duration on O2 uptake kinetics and severe-intensity exercise tolerance.

It has been suggested that a prior bout of high-intensity exercise has the potential to enhance performance during subsequent high-intensity exercise by accelerating the O(2) uptake (Vo(2)) on-response. However, the optimal combination of prior exercise intensity and subsequent recovery duration required to elicit this effect is presently unclear. Eight male participants, aged 18-24 yr, completed step cycle ergometer exercise tests to 80% of the difference between the preestablished gas exchange threshold and maximal Vo(2) (i.e., 80%Delta) after no prior exercise (control) and after six different combinations of prior exercise intensity and recovery duration: 40%Delta with 3 min (40-3-80), 9 min (40-9-80), and 20 min (40-20-80) of recovery and 70%Delta with 3 min (70-3-80), 9 min (70-9-80), and 20 min (70-20-80) of recovery. Overall Vo(2) kinetics were accelerated relative to control in all conditions except for 40-9-80 and 40-20-80 conditions as a consequence of a reduction in the Vo(2) slow component amplitude; the phase II time constant was not significantly altered with any prior exercise/recovery combination. Exercise tolerance at 80%Delta was improved by 15% and 30% above control in the 70-9-80 and 70-20-80 conditions, respectively, but was impaired by 16% in the 70-3-80 condition. Prior exercise at 40%Delta did not significantly influence exercise tolerance regardless of the recovery duration. These data demonstrate that prior high-intensity exercise ( approximately 70%Delta) can enhance the tolerance to subsequent high-intensity exercise provided that it is coupled with adequate recovery duration (>or=9 min). This combination presumably optimizes the balance between preserving the effects of prior exercise on Vo(2) kinetics and providing sufficient time for muscle homeostasis (e.g., muscle phosphocreatine and H(+) concentrations) to be restored.

Influence of hyperoxia on pulmonary O2 uptake kinetics following the onset of exercise in humans

The purpose of this study was to examine the influence of hyperoxic gas (50% O2 in N2) inspiration on pulmonary oxygen uptake (V(O2)) kinetics during step transitions to moderate, severe and supra-maximal intensity cycle exercise. Seven healthy male subjects completed repeat transitions to moderate (90% of the gas exchange threshold, GET), severe (70% of the difference between the GET and V(O2) peak) and supra-maximal (105% V(O2) peak) intensity work rates while breathing either normoxic (N) or hyperoxic (H) gas before and during exercise. Hyperoxia had no significant effect on the Phase II V(O2) time constant during moderate (N: 28+/-3s versus H: 31+/-7s), severe (N: 32+/-9s versus H: 33+/-6s) or supra-maximal (N: 37+/-9s versus H: 37+/-9s) exercise. Hyperoxia resulted in a 45% reduction in the amplitude of the V(O2) slow component during severe exercise (N: 0.60+/-0.21 L min(-1) versus H: 0.33+/-0.17 L min(-1); P < 0.05) and a 15% extension of time to exhaustion during supra-maximal exercise (N: 173+/-28 s versus H: 198+/-41 s; P < 0.05). These results indicate that the Phase II V(O2) kinetics are not normally constrained by (diffusional) O2 transport limitations during moderate, severe or supra-maximal intensity exercise in young healthy subjects performing upright cycle exercise.

Influence of pacing strategy on O2 uptake and exercise tolerance

Seven male subjects completed cycle exercise bouts to the limit of tolerance on three occasions: (1) at a constant work rate (340±57 W; even‐pace strategy; ES); (2) at a work rate that was initially 10% lower than that in the ES trial but which then increased with time such that it was 10% above that in the ES trial after 120 s of exercise (slow‐start strategy; SS); and, (3) at a work rate that was initially 10% higher than that in the ES trial but which then decreased with time such that it was 10% below that in the ES trial after 120 s of exercise (fast‐start strategy; FS). The expected time to exhaustion predicted from the pre‐established power–time relationship was 120 s in all three conditions. However, the time to exhaustion was significantly greater (P<0.05) for the FS (174±56 s) compared with the ES (128±21 s) and SS (128±30 s) conditions. In the FS condition, V̇O2 increased more rapidly toward its peak such that the total O2 consumed in the first 120 s of exercise was greater (ES: 5.15±0.78; SS: 5.07±0.83; FS: 5.36±0.84 L; P<0.05 for FS vs ES and SS). These results suggest that a fast‐start pacing strategy might enhance exercise tolerance by increasing the oxidative contribution to energy turnover and hence “sparing” some of the finite anaerobic capacity across the transition to high‐intensity exercise.

Influence of recombinant human erythropoietin treatment on pulmonary O2 uptake kinetics during exercise in humans

We hypothesized that 4 weeks of recombinant human erythropoietin (RhEPO) treatment would result in a significant increase in haemoglobin concentration ([Hb]) and arterial blood O2‐carrying capacity and that this would (1) increase peak pulmonary oxygen uptake during ramp incremental exercise, and (2) speed kinetics during ‘severe’‐, but not ‘moderate’‐ or ‘heavy’‐intensity, step exercise. Fifteen subjects (mean ±s.d. age 25 ± 4 years) were randomly assigned to either an experimental group which received a weekly subcutaneous injection of RhEPO (150 IU kg−1; n= 8), or a control group (CON) which received a weekly subcutaneous injection of sterile saline (10 ml; n= 7) as a placebo, for four weeks. The subjects and the principal researchers were both blind with respect to the group assignment. Before and after the intervention period, all subjects completed a ramp test for determination of the gas exchange threshold (GET) and , and a number of identical ‘step’ transitions from ‘unloaded’ cycling to work rates requiring 80% GET (moderate), 70% of the difference between the GET and (heavy), and 105% (severe) as determined from the initial ramp test. Pulmonary gas exchange was measured breath‐by‐breath. There were no significant differences between the RhEPO and CON groups for any of the measurements of interest ([Hb], kinetics) before the intervention. Four weeks of RhEPO treatment resulted in a 7% increase both in [Hb] (from 15.8 ± 1.0 to 16.9 ± 0.7 g dl−1; P < 0.01) and (from 47.5 ± 4.2 to 50.8 ± 10.7 ml kg−1·min−1; P < 0.05), with no significant change in CON. RhEPO had no significant effect on kinetics for moderate (Phase II time constant, from 28 ± 8 to 28 ± 7 s), heavy (from 37 ± 12 to 35 ± 11 s), or severe (from 33 ± 15 to 35 ± 15 s) step exercise. Our results indicate that enhancing blood O2‐carrying capacity and thus the potential for muscle O2 delivery with RhEPO treatment enhanced the peak but did not influence kinetics, suggesting that the latter is principally regulated by intracellular (metabolic) factors, even during exercise where the requirement is greater than the , at least in young subjects performing upright cycle exercise.

Influence of nitric oxide synthase inhibition on pulmonary O2 uptake kinetics during supra‐maximal exercise in humans

We have recently reported that inhibition of nitric oxide synthase (NOS) with NG‐nitro‐l‐arginine methyl ester (l‐NAME) accelerates the ‘phase II’ pulmonary O2 uptake kinetics following the onset of moderate and heavy intensity submaximal exercise in humans. These data suggest that the influence of nitric oxide (NO) on mitochondrial function is an important factor in the inertia to aerobic respiration that is evident in the transition from a lower to a higher metabolic rate. The purpose of the present study was to investigate the influence of l‐NAME on pulmonary kinetics following the onset of supra‐maximal exercise, where it has been suggested that O2 availability represents an additional limitation to kinetics. Seven healthy young men volunteered to participate in this study. Following an incremental cycle ergometer test for the determination of , the subjects returned on two occasions to perform a ‘step’ exercise test from a baseline of unloaded cycling to a work rate calculated to require 105%, preceded either by systemic infusion of l‐NAME (4 mg kg−1 in 50 ml saline) or 50 ml saline as a control (Con). Pulmonary gas exchange was measured on a breath‐by‐breath basis throughout the exercise tests. The duration of ‘phase I’ was greater with l‐NAME (Con: 14.0 ± 2.1 versusl‐NAME: 16.0 ± 1.6 s; P= 0.03), suggestive of a slower cardiovascular adaptation following the onset of exercise. However, the phase II time constant was reduced by 44% with l‐NAME (Con: 36.3 ± 17.3 versusl‐NAME: 20.4 ± 8.3 s; P= 0.01). The accumulation of blood lactate during exercise was also reduced with l‐NAME (Con: 4.0 ± 1.1 versusl‐NAME: 2.7 ± 2.1 mm; P= 0.04). These data indicate that skeletal muscle NO production represents an important limitation to the acceleration of oxidative metabolism following the onset of supra‐maximal exercise in humans.

Influence of initial metabolic rate on pulmonary O2 uptake on-kinetics during severe intensity exercise

We hypothesised that the fundamental (Phase II) component of pulmonary oxygen uptake (VO(2)) kinetics would be significantly slower when step transitions to severe intensity cycle exercise were initiated from elevated baseline metabolic rates, and that this would be associated with evidence for a greater activation of higher-order (i.e. type II) muscle fibres. Seven male subjects (age 22-34 years) completed repeat step transitions to a severe (S) work rate, estimated to require 100% VO(2) peak, from a baseline of: (1) 3 min of unloaded cycling (L-->S); (2) 6 min of moderate exercise (M-->S); (3) 6 min of heavy exercise (H-->S). Pulmonary gas exchange and the electromyogram (EMG) of the m. vastus lateralis were measured throughout all exercise tests. The Phase II VO(2) kinetics became progressively slower at higher baseline metabolic rates (tau was 37 +/- 6, 59 +/- 23, and 93 +/- 50 s for L-->S, M-->S, and H-->S, respectively; P < 0.05 between L-->S and H-->S). Both the integrated EMG and the mean power frequency were significantly higher immediately before the step transition to severe exercise when it was initiated from higher metabolic rates. Although indirect, these data suggest that the slower Phase II VO(2) kinetics observed at higher baseline metabolic rates was related to alterations in muscle activation and fibre recruitment patterns.