Search

Dietary nitrate (NO

We report the physiological characteristics and O2 cost of running overground at ∼21.1 km/h in a cohort of the world’s best male distance runners. We provide new information on the absolute and relative O2 uptake required to run at 2-h marathon pace.

Introduction Men and women joining the military undergo the same training, often in mixed-sex platoons. Given the inherent physiological and physical performance differences between men and women, it is reasonable to question whether sex differences exist in the adaptation to military training and, therefore, whether sex-specific training should be employed to optimise training adaptations. Objective To systematically review the literature evaluating changes in the physical performance of men and women following military training. Methods Six database sources were searched in addition to extensive secondary searching. Primary prospective intervention studies (all designs) evaluating physical training interventions in military populations, reporting pre- to post-training changes in physical fitness outcomes for both women and men, were included. Results We screened 3966 unique records. Twenty-nine studies (n = 37 study reports) were included, most of which were conducted in the USA and evaluated initial training for military recruits. Positive changes were more consistently observed in aerobic fitness and muscle strength (whole body and upper body) outcomes than lower body strength, muscle power or muscle endurance outcomes, following physical training. Relative pre- to post-training changes for all outcome measures tended to be greater in women than men although few statistically significant sex by outcome/time interactions were observed. Conclusion Improvements in some, but not all, performance components were observed following a period of military training. Largely, these improvements were not significantly different between sexes. Further prospective research is needed to evaluate sex-specific differences in the response to physical training in controlled conditions to improve military physical training outcomes for both sexes. Electronic supplementary material The online version of this article (10.1007/s40279-018-0983-4) contains supplementary material, which is available to authorized users.

Background - Chronic obstructive pulmonary disease (COPD) results in exercise intolerance. Dietary nitrate supplementation has been shown to lower blood pressure (BP), reduce the oxygen cost of exercise, and enhance exercise tolerance in healthy volunteers. This study assessed the effects of dietary nitrate on the oxygen cost of cycling, walking performance and BP in individuals with mild–moderate COPD.Methods - Thirteen patients with mild–moderate COPD were recruited. Participants consumed 70 ml of either nitrate-rich (6.77 mmol nitrate; beetroot juice) or nitrate-depleted beetroot juice (0.002 mmol nitrate; placebo) twice a day for 2.5 days, with the final supplement ~3 hours before testing. BP was measured before completing two bouts of moderate-intensity cycling, where pulmonary gas exchange was measured throughout. The six-minute walk test (6MWT) was completed 30 minutes subsequent to the second cycling bout.Results - Plasma nitrate concentration was significantly elevated following beetroot juice vs. placebo (placebo; 48 ± 86 vs. beetroot juice; 215 ± 84 µM, P = 0.002). No significant differences were observed between placebo vs. beetroot juice for oxygen cost of exercise (933 ± 323 vs. 939 ± 302 ml: min−1; P = 0.88), distance covered in the 6MWT (456 ± 86 vs. 449 ± 79 m; P = 0.37), systolic BP (123 ± 14 vs. 123 ± 14 mmHg; P = 0.91), or diastolic BP (77 ± 9 vs. 79 ± 9 mmHg; P = 0.27).Conclusion - Despite a large rise in plasma nitrate concentration, two days of nitrate supplementation did not reduce the oxygen cost of moderate intensity cycling, increase distance covered in the 6MWT, or lower BP.

We investigated the influence of hypoxia on the asymptote (critical power, CP) and the curvature constant (W') of the hyperbolic power-duration relationship, as measured by both conventional and all-out testing procedures. 13 females completed 5 constant-power prediction trials and a 3-min all-out test to estimate CP and W', in both normoxia (N) and moderate hypoxia (H; FiO2=0.13). CP was significantly reduced in hypoxia compared to normoxia when estimated by conventional (H:132±17 vs. N:175±25 W; P0.001) and all-out methods (H:134±23 vs. N:172±30 W; P0.01). The W' was not significantly different in hypoxia compared to normoxia when established by conventional (H:12.3±2.7 vs. N:13.2±2.2 kJ) and all-out methods (H:12.0±2.6 vs. N:12.5±1.4 kJ). Estimates of CP and W' obtained with conventional and all-out methods were not significantly different either in normoxia or hypoxia. There was a significant relationship between the % change in CP relative to V̇(O2peak) and the % change in W' in normoxia compared to hypoxia (r=0.83, P0.001; conventional test). Changes in the W' in hypoxia are related to changes in the CP relative to V̇(O2peak), suggesting that the W' may not be defined simply as an 'anaerobic' energy store.

Nitric oxide alters gastric blood flow, improves vascular function and mediates glucose uptake within the intestines and skeletal muscle. Dietary nitrate, acting as a source of nitric oxide, appears to be a potential low cost therapy that may help maintain glucose homeostasis. In a randomised, double-blind, placebo-controlled crossover study, 31 young and older adult participants had a standardised breakfast, supplemented with either nitrate rich beetroot juice (11.91 mmol nitrate) or nitrate depleted beetroot juice as placebo (0.01 mmol nitrate). MRI was used to assess apparent diffusion coefficient (ADC), portal vein flux and velocity. Plasma glucose, incretin and C-peptide concentrations and BP were assessed. Outcome variables were measured at baseline and hourly for 3 hours. Compared with a placebo, beetroot juice resulted in a significant elevation in plasma nitrate and plasma nitrite concentration. No differences were seen for the young or older adult cohorts between placebo and beetroot juice for ADC, or portal vein flux. There was an interaction effect in the young adults, which was absent in the older adults between visits for portal vein velocity. Nitrate supplementation did not reduce plasma glucose active GLP-1, total GLP-1 or plasma C-peptide concentrations for the young or older adult cohorts. Despite a significant elevation in plasma nitrite concentration following an acute dose of 11.91 mmol of nitrate, there was no effect on hepatic blood flow, plasma glucose, C-peptide, or incretin concentration in healthy adults.

We tested the hypothesis that incremental cycling to exhaustion that is paced using clamps of the rating of perceived exertion (RPE) elicits higher \( \dot{V}_{{{\text{O}}_{2} { \max }}} \) values compared to a conventional ramp incremental protocol when test duration is matched. Seven males completed three incremental tests to exhaustion to measure \( \dot{V}_{{{\text{O}}_{2} { \max }}} \). The incremental protocols were of similar duration and included: a ramp test at 30 W min−1 with constant cadence (RAMP1); a ramp test at 30 W min−1 with cadence free to fluctuate according to subject preference (RAMP2); and a self-paced incremental test in which the power output was selected by the subject according to prescribed increments in RPE (SPT). The subjects also completed a \( \dot{V}_{{{\text{O}}_{2} { \max }}} \) ‘verification’ test at a fixed high-intensity power output and a 3-min all-out test. No difference was found for \( \dot{V}_{{{\text{O}}_{2} { \max }}} \) between the incremental protocols (RAMP1 = 4.33 ± 0.60 L min−1; RAMP2 = 4.31 ± 0.62 L min−1; SPT = 4.36 ± 0.59 L min−1; P > 0.05) nor between the incremental protocols and the peak \( \dot{V}_{{{\text{O}}_{2} }} \) measured during the 3-min all-out test (4.33 ± 0.68 L min−1) or the \( \dot{V}_{{{\text{O}}_{2} { \max }}} \) measured in the verification test (4.32 ± 0.69 L min−1). The integrated electromyogram, blood lactate concentration, heart rate and minute ventilation at exhaustion were not different (P > 0.05) between the incremental protocols. In conclusion, when test duration is matched, SPT does not elicit a higher \( \dot{V}_{{{\text{O}}_{2} { \max }}} \) compared to conventional incremental protocols. The striking similarity of \( \dot{V}_{{{\text{O}}_{2} { \max }}} \) measured across an array of exercise protocols indicates that there are physiological limits to the attainment of \( \dot{V}_{{{\text{O}}_{2} { \max }}} \) that cannot be exceeded by self-pacing.

Following the start of low-intensity exercise in healthy humans, it has been established that the kinetics of skeletal muscle O(2) delivery is faster than, and does not limit, the kinetics of muscle O(2) uptake (V(O(2)(m))). Direct data are lacking, however, on the question of whether O(2) delivery might limit (V(O(2)(m))) kinetics during high-intensity exercise. Using multiple exercise transitions to enhance confidence in parameter estimation, we therefore investigated the kinetics of, and inter-relationships between, muscle blood flow (Q(m)), a-(V(O(2))) difference and (V(O(2)(m))) following the onset of low-intensity (LI) and high-intensity (HI) exercise. Seven healthy males completed four 6 min bouts of LI and four 6 min bouts of HI single-legged knee-extension exercise. Blood was frequently drawn from the femoral artery and vein during exercise and Q(m), a-(V(O(2))) difference and (V(O(2)(m))) were calculated and subsequently modelled using non-linear regression techniques. For LI, the fundamental component mean response time (MRT(p)) for Q(m) kinetics was significantly shorter than (V(O(2)(m))) kinetics (mean ± SEM, 18 ± 4 vs. 30 ± 4 s; P < 0.05), whereas for HI, the MRT(p) for Q(m) and (V(O(2)(m))) was not significantly different (27 ± 5 vs. 29 ± 4 s, respectively). There was no difference in the MRT(p) for either Q(m) or (V(O(2)(m))) between the two exercise intensities; however, the MRT(p)for a-(V(O(2)) difference was significantly shorter for HI compared with LI (17 ± 3 vs. 28 ± 4 s; P < 0.05). Excess O(2), i.e. oxygen not taken up (Q(m) x (V(O(2))), was significantly elevated within the first 5 s of exercise and remained unaltered thereafter, with no differences between LI and HI. These results indicate that bulk O(2) delivery does not limit (V(O(2)(m))) kinetics following the onset of LI or HI knee-extension exercise.

A single 3-min all-out cycling test can be used to estimate the power asymptote (critical power, CP) and the curvature constant (W') of the power-duration relationship for severe-intensity exercise. It was hypothesized that when exercise immediately preceding the 3-min all-out test was performedCP, the CP and W' parameters would be unaffected, whereas preceding exerciseCP would systematically reduce the W' without affecting the CP. Seven physically active males completed 3-min all-out cycling tests in randomized order immediately preceded by: unloaded cycling (control); 6-min moderate; 6-min heavy; 2-min severe (S2); or 4-min severe (S4) intensity exercise. The CP was estimated from the mean power output over the final 30 s of the test and the W' was estimated as the power-time integral above end-test power. There were no significant differences in the CP between control (279 ± 62), moderate (275 ± 52), heavy (286 ± 66 W), S2 (274 ± 55), or S4 (273 ± 65 W). The W' was significantly lower (P0.05) in S2 (11.5 ± 2.5) and S4 (8.9 ± 2.2) than in control (16.3 ± 2.3), moderate (17.2 ± 2.4) and heavy (15.6 ± 2.3 kJ). These results support the notion that the W' is predictably depleted only at a power outputCP whereas the CP is independent of the mechanisms which reduce W'.

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).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.BR supplementation elevated plasma [nitrite] (PL = 241 ± 125 vs BR = 575 ± 199 nM, P0.05). The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance (P0.05), but BR significantly increased mean PO during the 4-km (PL = 279 ± 51 vs BR = 292 ± 44 W, P0.05) and 16.1-km TT (PL = 233 ± 43 vs BR = 247 ± 44 W, P0.01). Consequently, BR improved 4-km performance by 2.8% (PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min, P0.05) and 16.1-km performance by 2.7% (PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min, P0.01).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.

Purpose: The purpose of this study was to investigate the influence of pacing strategy on pulmonary V?O2 kinetics and performance during high-intensity exercise. Methods: Seven males completed 3- and 6-min bouts of cycle exercise on three occasions with the bouts initiated using an even-start (ES; constant work rate), fast-start (FS), or slow-start (SS) pacing strategy. In all conditions, subjects completed an all-out sprint over the final 60 s of the test as a measure of performance. Results: For the 3-min exercise bouts, the mean response time (MRT) for the V?O2 kinetics over the pacing phase was shortest in FS (35 ± 6 s), longest in SS (55 ± 14 s), and intermediate in ES (41 ± 10 s) (P < 0.05 for all comparisons). For the 6-min bouts, the V?O2 MRT was longer in SS (56 ± 15 s) than that in FS and ES (38 ± 7 and 42 ± 6 s, respectively, P < 0.05). The V?O2 at the end of exercise was not different from the V?O2max during the 6-min exercise bouts or 3-FS but was lower than V?O2max for 3-ES and 3-SS (P < 0.05). The end-sprint performance was significantly enhanced in 3-FS compared with 3-ES and 3-SS (mean power = 374 ± 68 vs 348 ± 61 and 345 ± 71 W, respectively; P < 0.05). However, end-sprint performance was unaffected by pacing strategy in the 6-min bouts. Conclusions: These data indicate that an FS pacing strategy significantly improves performance during 3-min bouts of high-intensity exercise by speeding V?O2 kinetics and enabling the attainment of V?O2max

We investigated the influence of the antioxidant N-acetylcysteine (NAC) on plasma nitrite concentration ([NO₂⁻]), pulmonary oxygen uptake (V(O₂)) kinetics and exercise tolerance. Eight males completed 'step' moderate- and severe-intensity cycle exercise tests following infusion of either NAC (125 mg kg⁻¹ h⁻¹ for 15 min followed by 25 mg kg⁻¹ h⁻¹ until the termination of exercise) or Placebo (PLA; saline). Following the initial loading phase, NAC infusion elevated plasma free sulfhydryl groups compared to placebo (PLA: 4 ± 2 vs. NAC: 13 ± 3 μ M g⁻¹; P 0.05), there was appreciable inter-subject variability in the response: four subjects had small reductions in exercise tolerance with NAC compared to PLA (-4%, -8%, -11%, and -14%) while the other four showed substantial improvements (+24%, +24%, +40%, and +69%). The results suggest that exercise-induced redox perturbations may contribute to fatigue development in recreationally-active adults.

The purpose of this study was to elucidate the mechanistic bases for the reported reduction in the O2cost of exercise following short-term dietary nitrate (NO3−) supplementation. In a randomized, double-blind, crossover study, seven men (aged 19–38 yr) consumed 500 ml/day of either nitrate-rich beetroot juice (BR, 5.1 mmol of NO3−/day) or placebo (PL, with negligible nitrate content) for 6 consecutive days, and completed a series of low-intensity and high-intensity “step” exercise tests on the last 3 days for the determination of the muscle metabolic (using31P-MRS) and pulmonary oxygen uptake (V̇o2) responses to exercise. On days 4–6, BR resulted in a significant increase in plasma [nitrite] (mean ± SE, PL 231 ± 76 vs. BR 547 ± 55 nM; P < 0.05). During low-intensity exercise, BR attenuated the reduction in muscle phosphocreatine concentration ([PCr]; PL 8.1 ± 1.2 vs. BR 5.2 ± 0.8 mM; P < 0.05) and the increase in V̇o2(PL 484 ± 41 vs. BR 362 ± 30 ml/min; P < 0.05). During high-intensity exercise, BR reduced the amplitudes of the [PCr] (PL 3.9 ± 1.1 vs. BR 1.6 ± 0.7 mM; P < 0.05) and V̇o2(PL 209 ± 30 vs. BR 100 ± 26 ml/min; P < 0.05) slow components and improved time to exhaustion (PL 586 ± 80 vs. BR 734 ± 109 s; P < 0.01). The total ATP turnover rate was estimated to be less for both low-intensity (PL 296 ± 58 vs. BR 192 ± 38 μM/s; P < 0.05) and high-intensity (PL 607 ± 65 vs. BR 436 ± 43 μM/s; P < 0.05) exercise. Thus the reduced O2cost of exercise following dietary NO3−supplementation appears to be due to a reduced ATP cost of muscle force production. The reduced muscle metabolic perturbation with NO3−supplementation allowed high-intensity exercise to be tolerated for a greater period of time.

Metabolic transitions from rest to high-intensity exercise were divided into two discrete steps (i.e., rest-to-moderate-intensity (R--M) and moderate-to-high-intensity (M--H)) to explore the effect of prior high-intensity 'priming' exercise on intramuscular [PCr] and pulmonary VO₂ kinetics for different sections of the motor unit pool. It was hypothesized that [PCr] and VO₂ kinetics would be unaffected by priming during R--M exercise, but that the time constants (tau) describing the fundamental [PCr] response and the phase II VO₂ response would be significantly reduced by priming for M--H exercise. On three separate occasions, six male subjects completed two identical R--M/M--H 'work-to-work' prone knee-extension exercise bouts separated by 5min rest. Two trials were performed with measurement of pulmonary VO₂ and the integrated electromyogram (iEMG) of the right m. vastus lateralis. The third trial was performed within the bore of a 1.5-T superconducting magnet for (31)P-MRS assessment of muscle metabolic responses. Priming did not significantly affect the [PCr] or VO₂ tau during R--M ([PCr] tau Unprimed: 24+/-16 vs. Primed: 22+/-14s; VO₂ tau Unprimed: 26+/-8 vs. Primed: 25+/-9s) or M--H transitions ([PCr] tau Unprimed: 30+/-5 vs. Primed: 32+/-7s; VO₂ tau Unprimed: 37+/-5 vs. Primed: 38+/-9s). However, it did reduce the amplitudes of the [PCr] and VO₂ slow components by 50% and 46%, respectively, during M--H (P0.05 for both comparisons). These effects were accompanied by iEMG changes suggesting reduced muscle fiber activation during M--H exercise after priming. It is concluded that the tau for the initial exponential change of muscle [PCr] and pulmonary VO₂ following the transition from moderate-to-high-intensity prone knee-extension exercise is not altered by priming exercise.

We hypothesized that a short-term training program involving repeated all-out sprint training (RST) would be more effective than work-matched, low-intensity endurance training (ET) in enhancing the kinetics of oxygen uptake (V̇o2) and muscle deoxygenation {deoxyhemoglobin concentration ([HHb])} following the onset of exercise. Twenty-four recreationally active subjects (15 men, mean ± SD: age 21 ± 4 yr, height 173 ± 9 cm, body mass 71 ± 11 kg) were allocated to one of three groups: RST, which completed six sessions of four to seven 30-s RSTs; ET, which completed six sessions of work-matched, moderate-intensity cycling; and a control group (CON). All subjects completed moderate-intensity and severe-intensity “step” exercise transitions before (Pre) and after the 2-wk intervention period (Post). Following RST, [HHb] kinetics were speeded, and the amplitude of the [HHb] response was increased during both moderate and severe exercise ( P < 0.05); the phase II V̇o2 kinetics were accelerated for both moderate (Pre: 28 ± 8, Post: 21 ± 8 s; P < 0.01) and severe (Pre: 29 ± 5, Post: 23 ± 5 s; P < 0.05) exercise; the amplitude of the V̇o2 slow component was reduced (Pre: 0.52 ± 0.19, Post: 0.40 ± 0.17 l/min; P < 0.01); and exercise tolerance during severe exercise was improved by 53% (Pre: 700 ± 234, Post: 1,074 ± 431 s; P < 0.01). None of these parameters was significantly altered in the ET and CON groups. Six sessions of RST, but not ET, resulted in changes in [HHb] kinetics consistent with enhanced fractional muscle O2 extraction, faster V̇o2 kinetics, and an increased tolerance to high-intensity exercise.

The purpose of this investigation was to determine the contribution of muscle O(2) consumption (mVO2) to pulmonary O(2) uptake (pVO2) 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 mVO2 (direct Fick technique) and pVO2 (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 mVO2 and pVO2 were modelled using non-linear regression. The time constant (tau) describing the phase II pVO2 kinetics following the onset of exercise was not significantly different from the mean response time (initial time delay + tau) for mVO2 kinetics for LI (30 +/- 3 vs 30 +/- 3 s) but was slightly higher (P 0.05; r = -0.40). MTTc-l was approximately 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 pVO2 kinetics reflect mVO2 kinetics during exercise but not during recovery where caution in data interpretation is advised. Increased mVO2 probably makes a small contribution to during the first 15-20 s of exercise.

We hypothesized that increasing skeletal muscle total creatine (Cr) content through dietary Cr supplementation would result in slower muscle phosphocreatine concentration ([PCr]) kinetics, as assessed using31P magnetic resonance spectroscopy, following the onset and offset of both moderate-intensity (Mod) and heavy-intensity (Hvy) exercise. Seven healthy males (age 29 ± 6 yr, mean ± SD) completed a series of square-wave transitions to Mod and Hvy knee extensor exercise inside the bore of a 1.5-T superconducting magnet both before and after a 5-day period of Cr loading (4× 5 g/day of creatine monohydrate). Cr supplementation resulted in an ∼8% increase in the resting muscle [PCr]-to-[ATP] ratio (4.66 ± 0.27 vs. 5.04 ± 0.22; P < 0.05), consistent with a significant increase in muscle total Cr content consequent to the intervention. The time constant for muscle [PCr] kinetics was increased following Cr loading for Mod exercise (control: 15 ± 8 vs. Cr: 25 ± 9 s; P < 0.05) and subsequent recovery (control: 14 ± 8 vs. Cr: 27 ± 8 s; P < 0.05) and for Hvy exercise (control: 54 ± 18 vs. Cr: 72 ± 30 s; P < 0.05), but not for subsequent recovery (control: 41 ± 11 vs. Cr: 44 ± 6 s). The magnitude of the increase in [PCr] following Cr loading was correlated ( P < 0.05) with the extent of the slowing of the [PCr] kinetics for the moderate off-transient ( r = 0.92) and the heavy on-transient ( r = 0.71). These data demonstrate, for the first time in humans, that an increase in muscle [PCr] results in a slowing of [PCr] dynamics in exercise and subsequent recovery.

Unaccustomed eccentric exercise has a profound impact on muscle structure and function. However, it is not known whether associated microvascular dysfunction disrupts the matching of O2delivery (Q̇o2) to O2utilization (V̇o2). Near-infrared spectroscopy (NIRS) was used to test the hypothesis that eccentric exercise-induced muscle damage would elevate the muscle Q̇o2:V̇o2ratio during severe-intensity exercise while preserving the speed of the V̇o2kinetics at exercise onset. Nine physically active men completed “step” tests to severe-intensity exercise from an unloaded baseline on a cycle ergometer before (Pre) and 48 h after (Post) eccentric exercise (100 squats with a load corresponding to 70% of body mass). NIRS and breath-by-breath pulmonary V̇o2were measured continuously during the exercise tests and subsequently modeled using standard nonlinear regression techniques. There were no changes in phase II pulmonary V̇o2kinetics following the onset of exercise (time constant: Pre, 25 ± 4 s; Post, 24 ± 2 s; amplitude: Pre, 2.36 ± 0.23 l/min; Post, 2.37 ± 0.23 l/min; all P > 0.05). However, the primary (Pre, 14 ± 3 s; Post, 19 ± 3 s) and overall (Pre, 16 ± 4 s; Post, 21 ± 4 s) mean response time of the [HHb] response was significantly slower following eccentric exercise ( P < 0.05). The slower [HHb] kinetics observed following eccentric exercise is consistent with an increased Q̇o2:V̇o2ratio during transitions to severe-intensity exercise. We propose that unchanged primary phase V̇o2kinetics are associated with an elevated Q̇o2:V̇o2ratio that preserves blood-myocyte O2flux.

(31)Phosphate-magnetic resonance spectroscopy and near infrared spectroscopy (NIRS) were used for the simultaneous assessment of changes in quadriceps muscle metabolism and oxygenation during consecutive bouts of high-intensity exercise. Six male subjects completed two 6 min bouts of single-legged knee-extension exercise at 80% of the peak work rate separated by 6 min of rest while positioned inside the bore of a 1.5 T superconducting magnet. The total haemoglobin and oxyhaemoglobin concentrations in the area of the quadriceps muscle interrogated with NIRS were significantly higher in the baseline period prior to the second compared with the first exercise bout, consistent with an enhanced muscle oxygenation. Intramuscular phosphorylcreatine concentration ([PCr]) dynamics were not different over the fundamental region of the response (time constant for bout 1, 51 +/- 15 s versus bout 2, 52 +/- 17 s). However, the [PCr] dynamics over the entire response were faster in the second bout (mean response time for bout 1, 72 +/- 16 s versus bout 2, 57 +/- 8 s; P < 0.05), as a consequence of a greater fall in [PCr] in the fundamental phase and a reduction in the magnitude of the 'slow component' in [PCr] beyond 3 min of exercise (bout 1, 10 +/- 6% versus bout 2, 5 +/- 3%; P < 0.05). These data suggest that the increased muscle O(2) availability afforded by the performance of a prior bout of high-intensity exercise does not significantly alter the kinetics of [PCr] hydrolysis at the onset of a subsequent bout of high-intensity exercise. The greater fall in [PCr] over the fundamental phase of the response following prior high-intensity exercise indicates that residual fatigue acutely reduces muscle efficiency.

The kinetics of pulmonary O2 uptake is known to be substantially slower when exercise is initiated from a baseline of lower-intensity exercise rather than from rest. However, it is not known whether putative intracellular regulators of mitochondrial respiration (and in particular the phosphocreatine concentration, [PCr]) show similar non-linearities in their response dynamics. The purpose of this study was therefore to investigate the influence of baseline metabolic rate on muscle [PCr] kinetics (as assessed using 31P-magnetic resonance spectroscopy) following the onset of exercise. Seven male subjects completed ‘step’ tests to heavy-intensity exercise (80% of peak work-rate) from a resting baseline and also from a baseline of moderate-intensity exercise (40% of peak work-rate) using a single-leg knee-extensor ergometer situated inside the bore of a 1.5 T super-conducting magnet. The time constant describing the kinetics of the initial exponential-like fall in [PCr] was significantly different between rest-to-moderate (25 ± 14 s), rest-to-heavy (48 ± 11 s) and moderate-to-heavy exercise (95 ± 40 s) (P < 0.05 for all comparisons). A delayed-onset ‘slow component’ in the [PCr] response was observed in all subjects during rest-to-heavy exercise, but was attenuated in the moderate-to-heavy exercise condition. These data indicate that muscle [PCr] kinetics does not conform to ‘linear, first-order’ behaviour during dynamic exercise, and thus have implications for understanding the regulation of muscle oxidative metabolism.

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

We hypothesised that initiating heavy-intensity exercise from an elevated baseline metabolic rate would result in slower Phase II O2 uptake V(O2) kinetics and a greater overall 'gain' in V(O2) per unit increase in work rate. Seven healthy males performed a series of like-transitions on a cycle ergometer: (1) from light exercise to 'moderate' exercise (80% of the gas exchange threshold, GET; L--M); (2) from light exercise to 'heavy' exercise (40% of the difference between GET and V(O2) peak; L--H); (3) from moderate exercise to heavy exercise (M--H). The Phase II time constant (tau) was significantly (P0.01) greater in the M--H condition (48+/-11 s) compared to the L--M and L--H conditions (26+/-6 s versus 27+/-4 s, respectively). Moreover, the end-exercise 'gain' values were significantly different between the three conditions (L--M, 8.1+/-0.7 mL min-1 W-1; L--H, 9.7+/-0.4 mL min-1 W-1; M--H, 10.7+/-0.7 mL min-1 W-1; P0.05). This 'non-linearity' in the pulmonary V(O2) response to exercise might be attributed, at least in part, to differences in the metabolic properties of the muscle fibres recruited in the abrupt transition from a lower to a higher work rate.

Dietary nitrate supplementation has been shown to reduce the oxygen (O2) cost of exercise and enhance exercise tolerance in healthy individuals. This study assessed whether similar effects could be observed in individuals with type 2 diabetes (T2DM). In a randomized, double-blind, placebo-controlled crossover study, 48 participants with T2DM supplemented their diet for 4 days with either nitrate-rich beetroot juice (70 ml/day, 6.43 mmol nitrate/day) or nitrate-depleted beetroot juice as placebo (70 ml/day, 0.07 mmol nitrate/day). After each intervention period, resting plasma nitrate and nitrite concentrations were measured subsequent to participants completing moderate-paced walking. Pulmonary gas exchange was measured to assess the O2 cost of walking. After a rest period, participants performed the 6-min walk test (6MWT). Relative to placebo, beetroot juice resulted in a significant increase in plasma nitrate (placebo, 57±66 vs beetroot, 319±110 µM; P < 0.001) and plasma nitrite concentration (placebo, 680±256 vs beetroot, 1065±607 nM; P < 0.001). There were no differences between placebo juice and beetroot juice for the O2 cost of walking (946±221 vs 939±223 ml/min, respectively; P = 0.59) and distance covered in the 6MWT (550±83 vs 554±90 m, respectively; P = 0.17). Nitrate supplementation did not affect the O2 cost of moderate-paced walking or improve performance in the 6MWT. These findings indicate that dietary nitrate supplementation does not modulate the response to exercise in individuals with T2DM.

Purpose: The influence of metabolic alkalosis (ALK) on pulmonary O2 uptake (pV·O2) kinetics during high-intensity cycle exercise is controversial. The purpose of this study was to examine the influence of ALK induced by sodium bicarbonate (NaHCO3) ingestion on pV·O2 kinetics, using a sufficient number of repeat-step transitions to provide high confidence in the results obtained. Methods: Seven healthy males completed step tests to a work rate requiring 80% pV·O2max on six separate occasions: three times after ingestion of 0.3 g·kg-1 body mass NaHCO3 in 1 L of fluid, and three times after ingestion of a placebo (CON). Blood samples were taken to assess changes in acid-base balance, and pV·O2 was measured breath-by-breath. Results: NaHCO3 ingestion significantly increased blood pH and [bicarbonate] both before and during exercise relative to the control condition (P < 0.001). The time constant of the phase II pV·O2 response was not different between conditions (CON: 29 ± 6 vs ALK: 32 ± 7 s; P = 0.21). However, the onset of the pV·O2 slow component was delayed by NaHCO3 ingestion (CON: 120 ± 19 vs ALK: 147 ± 34 s; P < 0.01), resulting in a significantly reduced end-exercise pV·O2 (CON: 2.88 ± 0.19 vs ALK: 2.79 ± 0.23 L·min-1; P < 0.05). Conclusions: Metabolic alkalosis has no effect on phase II pV·O2 kinetics but alters the pV·O2 slow-component response, possibly as a result of the effects of NaHCO3 ingestion on muscle pH.

We hypothesized that 4 weeks of recombinant human erythropoietin (RhEPO) treatment would result in a significant increase in haemoglobin concentration ([Hb]) and arterial blood O(2)-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 O(2)-carrying capacity and thus the potential for muscle O(2) 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.

We have recently reported that inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine methyl ester (L-NAME) accelerates the 'phase II' pulmonary O2 uptake (VO2) 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 VO2 kinetics following the onset of supra-maximal exercise, where it has been suggested that O2 availability represents an additional limitation to VO2 kinetics. Seven healthy young men volunteered to participate in this study. Following an incremental cycle ergometer test for the determination of VO2max, 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% VO2max, 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 versus L-NAME: 16.0 +/- 1.6 s; P = 0.03), suggestive of a slower cardiovascular adaptation following the onset of exercise. However, the phase II VO2 time constant was reduced by 44% with L-NAME (Con: 36.3 +/- 17.3 versus L-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 versus L-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.

We hypothesized that the metabolic acidosis resulting from the performance of multiple-sprint exercise would enhance muscle perfusion and result in a speeding of pulmonary oxygen uptake (V̇o2) kinetics during subsequent perimaximal-intensity constant work rate exercise, if O2 availability represented a limitation to V̇o2 kinetics in the control (i.e., no prior exercise) condition. On two occasions, seven healthy subjects completed two bouts of exhaustive cycle exercise at a work rate corresponding to ∼105% of the predetermined V̇o2 peak, separated by 3 × 30-s maximal sprint cycling and 15-min recovery (MAX1 and MAX2). Blood lactate concentration (means ± SD: MAX1: 1.3 ± 0.4 mM vs. MAX2: 7.7 ± 0.9 mM; P < 0.01) was significantly greater immediately before, and heart rate was significantly greater both before and during, perimaximal exercise when it was preceded by multiple-sprint exercise. Near-infrared spectroscopy also indicated that muscle blood volume and oxygenation were enhanced when perimaximal exercise was preceded by multiple-sprint exercise. However, the time constant describing the primary component (i.e., phase II) increase in V̇o2 was not significantly different between the two conditions (MAX1: 33.8 ± 5.5 s vs. MAX2: 33.2 ± 7.7 s). Rather, the asymptotic “gain” of the primary V̇o2 response was significantly increased by the performance of prior sprint exercise (MAX1: 8.1 ± 0.9 ml·min−1·W−1 vs. MAX2: 9.0 ± 0.7 ml·min−1·W−1; P < 0.05), such that V̇o2 was projecting to a higher “steady-state” amplitude with the same time constant. These data suggest that priming exercise, which apparently increases muscle O2 availability, does not influence the time constant of the primary-component V̇o2 response but does increase the amplitude to which V̇o2 may rise following the onset of perimaximal-intensity cycle exercise.

We hypothesized that the effective inhibition of nitric oxide synthase (NOS), achieved via systemic infusion of NG-nitro-L-arginine methyl ester (L-NAME), would reduce the gas exchange threshold (GET) and the maximal oxygen uptake (O2max) during incremental cycle exercise in man if NO is important in the regulation of muscle vasodilatation. Seven healthy males, aged 18–34 years, volunteered to participate in this ethically approved study. On two occasions, the subjects completed an incremental exercise test to exhaustion on an electrically braked cycle ergometer following the infusion of either L-NAME (4 mg kg–1 in 50 ml saline) or placebo (50 ml saline, CON). At rest, the infusion of L-NAME resulted in a significant increase in mean arterial pressure (MAP; CON vs. L-NAME, 89 ± 8 vs. 103 ± 11 mmHg (mean ± S.D.; P < 0.05)) and a significant reduction in heart rate (HR; CON vs. L-NAME, 60 ± 12 vs. 51 ± 8 beats min–1; P < 0.01). At submaximal work rates, there was no significant difference in O2 between the conditions and no difference in the GET (CON vs. L-NAME, 1.94 ± 0.47 vs. 2.01 ± 0.41 l min–1). However, at higher work rates, differences in O2 between the conditions became more pronounced such that O2max was significantly lower with L-NAME (CON vs. L-NAME, 4.02 ± 0.41 vs. 3.80 ± 0.34 l min–1; P < 0.05). The reduction in O2max was associated with a reduction in HRmax (CON vs. L-NAME, 186 ± 10 vs. 178 ± 7 beats min–1; P < 0.01). These results demonstrate that NOS inhibition with L-NAME has no effect on GET but reduces O2max during large muscle group exercise in man, presumably by direct or indirect effects on cardiac output and muscle blood flow.

It has recently been reported that the 'gain' of Phase II increase in pulmonary oxygen uptake (i.e. the 'fundamental' increase in V(O(2)) per unit increase in work rate; G(p)) does not attain the anticipated value of approximately 10 ml min(-1)W(-1) following the onset of high-intensity exercise. In the present study, we hypothesised that G(p) would fall significantly below 10 ml min(-1)W(-1) only when the work rate exceeded the so-called 'critical power' (CP). Seven healthy males completed several 'square-wave' transitions from 'unloaded' cycling to work rates requiring 60 and 90% of the gas exchange threshold (GET), 40 and 80% of the difference between the GET and V(O(2)) peak (i.e. below and above the CP, respectively), and 100, 110 and 120% of V(O(2)) peak. Pulmonary V(O(2)) was measured breath-by-breath and V(O(2)) kinetics were determined using non-linear regression techniques. The asymptotic G(p) was significantly lower at work rates above (7.2-8.6 ml min(-1)W(-1)) compared to work rates below (9.3-9.7 ml min(-1)W(-1)) the CP (P < 0.05). We conclude that the gain of Phase II increase in V(O(2)) becomes significantly reduced when the work rate exceeds the CP.

KOPPO, K., D. P. WILKERSON, J. BOUCKAERT, S. WILMSHURST, I. T. CAMPBELL, and A. M. JONES. Influence of DCA on Pulmonary VO2 Kinetics during Moderate-Intensity Cycle Exercise. Med. Sci. Sports Exerc., Vol. 36, No. 7, pp. 1159–1164, 2004. To test the hypothesis that pharmacological activation of the pyruvate dehydrogenase enzyme complex (PDC) with dichloroacetate (DCA) would speed phase II pulmonary oxygen uptake (VO2) kinetics after the onset of subsequent moderate-intensity (40–45% VO2peak) cycle exercise. Seven healthy males (mean ± SD age 25 ± 4 yr, body mass 75.3 ± 9.4 kg) performed four “square-wave” transitions from unloaded cycling to a work rate requiring 90% of the predetermined gas exchange threshold either with or without prior infusion of DCA (50 mg·kg−1 body mass in 50 mL saline). Pulmonary VO2 was measured breath-by-breath in all tests and VO2 kinetics were determined from the averaged individual response to each condition using nonlinear regression techniques. The blood [lactate] measured immediately before the onset of exercise was significantly reduced in the DCA condition (C: 1.1 ± 0.3 vs DCA: 0.6 ± 0.3 mM; P < 0.01) consistent with successful activation of the PDC. However, DCA had no discernible effect on the rate at which VO2 increased toward the steady state after the onset of exercise as reflected in the phase II time constant (C: 28.5 ± 11.8 vs DCA: 29.4 ± 14.9 s). The results suggest that PDC activation does not represent a principal intramuscular limitation to VO2 kinetics after the onset of moderate-intensity exercise.

The present study examined if high intensity training (HIT) could increase the expression of oxidative enzymes in fast-twitch muscle fibers causing a faster oxygen uptake (V˙O2) response during intense (INT), but not moderate (MOD), exercise and reduce the V˙O2 slow component and muscle metabolic perturbation during INT. Pulmonary V˙O2 kinetics was determined in eight trained male cyclists (V˙O2-max: 59 ± 4 (means ± SD) mL min(-1) kg(-1)) during MOD (205 ± 12 W ~65% V˙O2-max) and INT (286 ± 17 W ~85% V˙O2-max) exercise before and after a 7-week HIT period (30-sec sprints and 4-min intervals) with a 50% reduction in volume. Both before and after HIT the content in fast-twitch fibers of CS (P < 0.05) and COX-4 (P < 0.01) was lower, whereas PFK was higher (P < 0.001) than in slow-twitch fibers. Content of CS, COX-4, and PFK in homogenate and fast-twitch fibers was unchanged with HIT. Maximal activity (μmol g DW(-1) min(-1)) of CS (56 ± 8 post-HIT vs. 59 ± 10 pre-HIT), HAD (27 ± 6 vs. 29 ± 3) and PFK (340 ± 69 vs. 318 ± 105) and the capillary to fiber ratio (2.30 ± 0.16 vs. 2.38 ± 0.20) was unaltered following HIT. V˙O2 kinetics was unchanged with HIT and the speed of the primary response did not differ between MOD and INT. Muscle creatine phosphate was lower (42 ± 15 vs. 66 ± 17 mmol kg DW(-1)) and muscle lactate was higher (40 ± 18 vs. 14 ± 5 mmol kg DW(-1)) at 6 min of INT (P < 0.05) after compared to before HIT. A period of intensified training with a volume reduction did not increase the content of oxidative enzymes in fast-twitch fibers, and did not change V˙O2 kinetics.

The power asymptote (critical power [CP]) and curvature constant (W') of the power-duration relationship dictate the tolerance to severe-intensity exercise. We tested the hypothesis that dietary nitrate supplementation would increase the CP and/or the W' during cycling exercise.In a double-blind, randomized, crossover study, nine recreationally active male subjects supplemented their diet with either nitrate-rich concentrated beetroot juice (BR; 2 × 250 mL·d, ∼8.2 mmol·d nitrate) or a nitrate-depleted BR placebo (PL; 2 × 250 mL·d, ∼0.006 mmol·d nitrate). In each condition, the subjects completed four separate severe-intensity exercise bouts to exhaustion at 60% of the difference between the gas exchange threshold and the peak power attained during incremental exercise (60% Δ), 70% Δ, 80% Δ, and 100% peak power, and the results were used to establish CP and W'.Nitrate supplementation improved exercise tolerance during exercise at 60% Δ (BR, 696 ± 120 vs PL, 593 ± 68 s; P0.05), 70% Δ (BR, 452 ± 106 vs PL, 390 ± 86 s; P0.05), and 80% Δ (BR, 294 ± 50 vs PL, 263 ± 50 s; P0.05) but not 100% peak power (BR, 182 ± 37 vs PL, 166 ± 26 s; P = 0.10). Neither CP (BR, 221 ± 27 vs PL, 218 ± 26 W) nor W' (BR, 19.3 ± 4.6 vs PL, 17.8 ± 3 kJ) were significantly altered by BR.Dietary nitrate supplementation improved endurance during severe-intensity exercise in recreationally active subjects without significantly increasing either the CP or the W'.

AB Purpose: We investigated the influence of pacing strategy on the work completed above critical power (CP) before exhaustion (W>CP) and the peak V[spacing dot above]O2 attained during high-intensity cycling. Methods: After the determination of V[spacing dot above]O2max from a ramp incremental cycling (INC) test and the estimation of the parameters of the power-duration relationship for high-intensity exercise (i.e., CP and W') from a 3-min all-out cycling test (AOT), eight male subjects completed a cycle test to exhaustion at a severe-intensity constant work rate (CWR) estimated to result in exhaustion in 3 min and a self-paced 3-min cycling time trial (SPT). Results: The V[spacing dot above]O2max determined from INC was 4.24 +/- 0.69 L[middle dot]min-1, and the CP and the W' estimated from AOT were 260 +/- 60 W and 16.5 +/- 4.0 kJ, respectively. W>CP during SPT was not significantly different from W>CP during CWR (15.3 +/- 5.6 and 16.6 +/- 7.4 kJ, respectively), and these values were also similar to W>CP during INC (16.4 +/- 4.0 kJ) and W' estimated from AOT. The peak V[spacing dot above]O2 during SPT was not significantly different from peak V[spacing dot above]O2 during CWR (4.20 +/- 0.77 and 4.14 +/- 0.75 L[middle dot]min-1, respectively), and these values were similar to the V[spacing dot above]O2max determined from INC and the peak V[spacing dot above]O2 during AOT (4.10 +/- 0.79 L[middle dot]min-1). Conclusion: Exhaustion during high-intensity exercise coincides with the achievement of the same peak V[spacing dot above]O2 (V[spacing dot above]O2max) and the completion of the same W>CP, irrespective of the work rate forcing function (INC or CWR) or pacing strategy (enforced pace or self-paced). These findings indicate that exhaustion during high-intensity exercise is based on highly predictable physiological processes, which are unaffected when pacing strategy is self-selected

Following the start of low-intensity exercise in healthy humans, it has been established that the kinetics of skeletal muscle O(2) delivery is faster than, and does not limit, the kinetics of muscle O(2) uptake (V(O(2)(m))). Direct data are lacking, however, on the question of whether O(2) delivery might limit (V(O(2)(m))) kinetics during high-intensity exercise. Using multiple exercise transitions to enhance confidence in parameter estimation, we therefore investigated the kinetics of, and inter-relationships between, muscle blood flow (Q(m)), a-(V(O(2))) difference and (V(O(2)(m))) following the onset of low-intensity (LI) and high-intensity (HI) exercise. Seven healthy males completed four 6 min bouts of LI and four 6 min bouts of HI single-legged knee-extension exercise. Blood was frequently drawn from the femoral artery and vein during exercise and Q(m), a-(V(O(2))) difference and (V(O(2)(m))) were calculated and subsequently modelled using non-linear regression techniques. For LI, the fundamental component mean response time (MRT(p)) for Q(m) kinetics was significantly shorter than (V(O(2)(m))) kinetics (mean ± SEM, 18 ± 4 vs. 30 ± 4 s; P0.05), whereas for HI, the MRT(p) for Q(m) and (V(O(2)(m))) was not significantly different (27 ± 5 vs. 29 ± 4 s, respectively). There was no difference in the MRT(p) for either Q(m) or (V(O(2)(m))) between the two exercise intensities; however, the MRT(p)for a-(V(O(2)) difference was significantly shorter for HI compared with LI (17 ± 3 vs. 28 ± 4 s; P0.05). Excess O(2), i.e. oxygen not taken up (Q(m) x (V(O(2))), was significantly elevated within the first 5 s of exercise and remained unaltered thereafter, with no differences between LI and HI. These results indicate that bulk O(2) delivery does not limit (V(O(2)(m))) kinetics following the onset of LI or HI knee-extension exercise.

Dietary nitrate supplementation has been reported to improve short distance time trial (TT) performance by 1-3 % in club-level cyclists. It is not known if these ergogenic effects persist in longer endurance events or if dietary nitrate supplementation can enhance performance to the same extent in better trained individuals. Eight well-trained male cyclists performed two laboratory-based 50 mile TTs: (1) 2.5 h after consuming 0.5 L of nitrate-rich beetroot juice (BR) and (2) 2.5 h after consuming 0.5 L of nitrate-depleted BR as a placebo (PL). BR significantly elevated plasma [NO(2) (-)] (BR: 472 ± 96 vs. PL: 379 ± 94 nM; P 0.05) and reduced completion time for the 50 mile TT by 0.8 % (BR: 136.7 ± 5.6 vs. PL: 137.9 ± 6.4 min), which was not statistically significant (P 0.05). There was a significant correlation between the increased post-beverage plasma [NO(2) (-)] with BR and the reduction in TT completion time (r = -0.83, P = 0.01). Power output (PO) was not different between the conditions at any point (P 0.05) but oxygen uptake ([Formula: see text]O(2)) tended to be lower in BR (P = 0.06), resulting in a significantly greater PO/[Formula: see text]O(2) ratio (BR: 67.4 ± 5.5 vs. PL: 65.3 ± 4.8 W L min(-1); P 0.05). In conclusion, acute dietary supplementation with beetroot juice did not significantly improve 50 mile TT performance in well-trained cyclists. It is possible that the better training status of the cyclists in this study might reduce the physiological and performance response to NO(3) (-) supplementation compared with the moderately trained cyclists tested in earlier studies.

The purpose of this investigation was to determine the influence of heat stress on the dynamics of muscle metabolic perturbation during high-intensity exercise. Seven healthy males completed single-legged knee-extensor exercise until the limit of tolerance on two separate occasions. In a randomized order the subjects underwent 40 min of lower-body immersion in warm water at 42°C prior to exercise (HOT) or received no prior thermal manipulation (CON). Following the intervention, muscle metabolism was measured at rest and throughout exercise using (31)P-MRS. The tolerable duration of high-intensity exercise was reduced by 36% after passive heating (CON: 474 ± 146 vs. HOT: 303 ± 76 s; P = 0.005). Intramuscular pH was lower over the first 60 s of exercise (CON: 7.05 ± 0.02 vs. HOT: 7.00 ± 0.03; P = 0.019) in HOT compared to CON. The rate of muscle [PCr] degradation during exercise was greater in the HOT condition (CON: -0.17 ± 0.08 vs. HOT: -0.25 ± 0.10% s(-1); P = 0.006) and pH also tended to change more rapidly in HOT (P = 0.09). Muscle [PCr] (CON: 26 ± 14 vs. HOT: 29 ± 10%), [Pi] (CON: 504 ± 236 vs. HOT: 486 ± 186%) and pH (CON: 6.84 ± 0.13 vs. HOT: 6.80 ± 0.14; P > 0.05) were not statistically different at the limit of tolerance (P > 0.05 for all comparisons). These results suggest that the reduced time-to-exhaustion during high-intensity knee-extensor exercise following lower-body heating might be related, in part, to accelerated rates of change of intramuscular [PCr] and pH towards 'critical' values that limit muscle function.

There are reports of abnormal pulmonary oxygen uptake (V̇o2) and deoxygenated hemoglobin ([HHb]) kinetics in individuals with Type 2 diabetes (T2D) below 50 yr of age with disease durations of 2 and muscle [HHb] kinetics in 12 older T2D patients with extended disease durations (age: 65 ± 5 years; disease duration 9.3 ± 3.8 years) and 12 healthy age-matched control participants (CON; age: 62 ± 6 years). Maximal oxygen uptake (V̇o2max) was determined via a ramp incremental cycle test and V̇o2 and [HHb] kinetics were determined during subsequent submaximal step exercise. The V̇o2max was significantly reduced ( P < 0.05) in individuals with T2D compared with CON (1.98 ± 0.43 vs. 2.72 ± 0.40 l/min, respectively) but, surprisingly, V̇o2 kinetics was not different in T2D compared with CON (phase II time constant: 43 ± 17 vs. 41 ± 12 s, respectively). The Δ[HHb]/ΔV̇o2 was significantly higher in T2D compared with CON (235 ± 99 vs. 135 ± 33 AU·l−1·min−1; P < 0.05). Despite a lower V̇o2max, V̇o2 kinetics is not different in older T2D compared with healthy age-matched control participants. The elevated Δ[HHb]/ΔV̇o2 in T2D individuals possibly indicates a compromised muscle blood flow that mandates a greater O2 extraction during exercise. Longer disease duration may result in adaptations in the O2 extraction capabilities of individuals with T2D, thereby mitigating the expected age-related slowing of V̇o2 kinetics.

We investigated the influence of the antioxidant N-acetylcysteine (NAC) on plasma nitrite concentration ([NO₂⁻]), pulmonary oxygen uptake (V(O₂)) kinetics and exercise tolerance. Eight males completed 'step' moderate- and severe-intensity cycle exercise tests following infusion of either NAC (125 mg kg⁻¹ h⁻¹ for 15 min followed by 25 mg kg⁻¹ h⁻¹ until the termination of exercise) or Placebo (PLA; saline). Following the initial loading phase, NAC infusion elevated plasma free sulfhydryl groups compared to placebo (PLA: 4 ± 2 vs. NAC: 13 ± 3 μ M g⁻¹; P0.05) and this elevation was preserved throughout the protocol. The administration of NAC did not significantly influence plasma [NO₂⁻] or V(O₂) kinetics during either moderate- or severe-intensity exercise. Although NAC did not significantly alter severe-intensity exercise tolerance at the group mean level (PLA: 776 ± 181 vs. NAC: 878 ± 284 s; P0.05), there was appreciable inter-subject variability in the response: four subjects had small reductions in exercise tolerance with NAC compared to PLA (-4%, -8%, -11%, and -14%) while the other four showed substantial improvements (+24%, +24%, +40%, and +69%). The results suggest that exercise-induced redox perturbations may contribute to fatigue development in recreationally-active adults.

It has recently been reported that dietary nitrate (NO3−) supplementation, which increases plasma nitrite (NO2−) concentration, a biomarker of nitric oxide (NO) availability, improves exercise efficiency and exercise tolerance in healthy humans. We hypothesized that dietary supplementation with l-arginine, the substrate for NO synthase (NOS), would elicit similar responses. In a double-blind, crossover study, nine healthy men (aged 19–38 yr) consumed 500 ml of a beverage containing 6 g of l-arginine (Arg) or a placebo beverage (PL) and completed a series of “step” moderate- and severe-intensity exercise bouts 1 h after ingestion of the beverage. Plasma NO2− concentration was significantly greater in the Arg than the PL group (331 ± 198 vs. 159 ± 102 nM, P < 0.05) and systolic blood pressure was significantly reduced (123 ± 3 vs. 131 ± 5 mmHg, P < 0.01). The steady-state O2 uptake (V̇o2) during moderate-intensity exercise was reduced by 7% in the Arg group (1.48 ± 0.12 vs. 1.59 ± 0.14 l/min, P < 0.05). During severe-intensity exercise, the V̇o2 slow component amplitude was reduced (0.58 ± 0.23 and 0.76 ± 0.29 l/min in Arg and PL, respectively, P < 0.05) and the time to exhaustion was extended (707 ± 232 and 562 ± 145 s in Arg and PL, respectively, P < 0.05) following consumption of Arg. In conclusion, similar to the effects of increased dietary NO3− intake, elevating NO bioavailability through dietary l-Arg supplementation reduced the O2 cost of moderate-intensity exercise and blunted the V̇o2 slow component and extended the time to exhaustion during severe-intensity exercise.

Dietary nitrate (NO3−) supplementation with beetroot juice (BR) over 4–6 days has been shown to reduce the O2cost of submaximal exercise and to improve exercise tolerance. However, it is not known whether shorter (or longer) periods of supplementation have similar (or greater) effects. We therefore investigated the effects of acute and chronic NO3−supplementation on resting blood pressure (BP) and the physiological responses to moderate-intensity exercise and ramp incremental cycle exercise in eight healthy subjects. Following baseline tests, the subjects were assigned in a balanced crossover design to receive BR (0.5 l/day; 5.2 mmol of NO3−/day) and placebo (PL; 0.5 l/day low-calorie juice cordial) treatments. The exercise protocol (two moderate-intensity step tests followed by a ramp test) was repeated 2.5 h following first ingestion (0.5 liter) and after 5 and 15 days of BR and PL. Plasma nitrite concentration (baseline: 454 ± 81 nM) was significantly elevated (+39% at 2.5 h postingestion; +25% at 5 days; +46% at 15 days; P < 0.05) and systolic and diastolic BP (baseline: 127 ± 6 and 72 ± 5 mmHg, respectively) were reduced by ∼4% throughout the BR supplementation period ( P < 0.05). Compared with PL, the steady-state V̇o2during moderate exercise was reduced by ∼4% after 2.5 h and remained similarly reduced after 5 and 15 days of BR ( P < 0.05). The ramp test peak power and the work rate at the gas exchange threshold (baseline: 322 ± 67 W and 89 ± 15 W, respectively) were elevated after 15 days of BR (331 ± 68 W and 105 ± 28 W; P < 0.05) but not PL (323 ± 68 W and 84 ± 18 W). These results indicate that dietary NO3−supplementation acutely reduces BP and the O2cost of submaximal exercise and that these effects are maintained for at least 15 days if supplementation is continued.

Fatigue of the respiratory muscles during intense exercise might compromise leg blood flow, thereby constraining oxygen uptake (V̇o2) and limiting exercise tolerance. We tested the hypothesis that inspiratory muscle training (IMT) would reduce inspiratory muscle fatigue, speed V̇o2 kinetics and enhance exercise tolerance. Sixteen recreationally active subjects (mean ± SD, age 22 ± 4 yr) were randomly assigned to receive 4 wk of either pressure threshold IMT [30 breaths twice daily at ∼50% of maximum inspiratory pressure (MIP)] or sham treatment (60 breaths once daily at ∼15% of MIP). The subjects completed moderate-, severe- and maximal-intensity “step” exercise transitions on a cycle ergometer before (Pre) and after (Post) the 4-wk intervention period for determination of V̇o2 kinetics and exercise tolerance. There were no significant changes in the physiological variables of interest after Sham. After IMT, baseline MIP was significantly increased (Pre vs. Post: 155 ± 22 vs. 181 ± 21 cmH2O; P < 0.001), and the degree of inspiratory muscle fatigue was reduced after severe- and maximal-intensity exercise. During severe exercise, the V̇o2 slow component was reduced (Pre vs. Post: 0.60 ± 0.20 vs. 0.53 ± 0.24 l/min; P < 0.05) and exercise tolerance was enhanced (Pre vs. Post: 765 ± 249 vs. 1,061 ± 304 s; P < 0.01). Similarly, during maximal exercise, the V̇o2 slow component was reduced (Pre vs. Post: 0.28 ± 0.14 vs. 0.18 ± 0.07 l/min; P < 0.05) and exercise tolerance was enhanced (Pre vs. Post: 177 ± 24 vs. 208 ± 37 s; P < 0.01). Four weeks of IMT, which reduced inspiratory muscle fatigue, resulted in a reduced V̇o2 slow-component amplitude and an improved exercise tolerance during severe- and maximal-intensity exercise. The results indicate that the enhanced exercise tolerance observed after IMT might be related, at least in part, to improved V̇o2 dynamics, presumably as a consequence of increased blood flow to the exercising limbs.

We manipulated the baseline metabolic rate and body position to explore the effect of the interaction between recruitment of discrete sections of the muscle fiber pool and muscle O2 delivery on pulmonary O2 uptake (V̇o2) kinetics during cycle exercise. We hypothesized that phase II V̇o2 kinetics (τp) in the transition from moderate- to severe-intensity exercise would be significantly slower in the supine than upright position because of a compromise to muscle perfusion and that a priming bout of severe-intensity exercise would return τp during supine exercise to τp during upright exercise. Eight male subjects [35 ± 13 (SD) yr] completed a series of “step” transitions to severe-intensity cycle exercise from an “unloaded” (20-W) baseline and a baseline of moderate-intensity exercise in the supine and upright body positions. τp was not significantly different between supine and upright exercise during transitions from a 20-W baseline to moderate- or severe-intensity exercise but was significantly greater during moderate- to severe-intensity exercise in the supine position (54 ± 19 vs. 38 ± 10 s, P < 0.05). Priming significantly reduced τp during moderate- to severe-intensity supine exercise (34 ± 9 s), returning it to a value that was not significantly different from τp in the upright position. This effect occurred in the absence of changes in estimated muscle fractional O2 extraction (from the near-infrared spectroscopy-derived deoxygenated Hb concentration signal), such that the priming-induced facilitation of muscle blood flow matched increased O2 utilization in the recruited fibers, resulting in a speeding of V̇o2 kinetics. These findings suggest that, during supine cycling, priming speeds V̇o2 kinetics by providing an increased driving pressure for O2 diffusion in the higher-order (i.e., type II) fibers, which would be recruited in the transition from moderate- to severe-intensity exercise and are known to be especially sensitive to limitations in O2 supply.

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 O2 uptake (V̇o2) 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 V̇o2 (i.e., 80%Δ) after no prior exercise (control) and after six different combinations of prior exercise intensity and recovery duration: 40%Δ with 3 min (40-3-80), 9 min (40-9-80), and 20 min (40-20-80) of recovery and 70%Δ with 3 min (70-3-80), 9 min (70-9-80), and 20 min (70-20-80) of recovery. Overall V̇o2 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 V̇o2 slow component amplitude; the phase II time constant was not significantly altered with any prior exercise/recovery combination. Exercise tolerance at 80%Δ 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%Δ did not significantly influence exercise tolerance regardless of the recovery duration. These data demonstrate that prior high-intensity exercise (∼70%Δ) can enhance the tolerance to subsequent high-intensity exercise provided that it is coupled with adequate recovery duration (≥9 min). This combination presumably optimizes the balance between preserving the effects of prior exercise on V̇o2 kinetics and providing sufficient time for muscle homeostasis (e.g., muscle phosphocreatine and H+ concentrations) to be restored.

We used extreme pedal rates to investigate the influence of muscle fibre recruitment on pulmonary V(O)(2) kinetics during unloaded-to-moderate-intensity (U--M), unloaded-to-high-intensity (U--H), and moderate-intensity to high-intensity (M--H) cycling transitions. Seven healthy men completed transitions to 60% of the difference between gas-exchange threshold and peak V(O)(2) from both an unloaded and a moderate-intensity (95% GET) baseline at cadences of 35 and 115rpm. Pulmonary gas exchange was measured breath-by-breath and iEMG of the m. vastus lateralis and m. gluteus maximus was measured during all tests. At 35rpm, the phase II time constant (tau(p)) values for U--M, U--H, and M--H were 26+/-7, 31+/-7 and 36+/-8s with the value for M--H being longer than for U--M (P0.05). At 115rpm, the tau(p) values for U--M, U--H, and M--H were 29+/-8, 48+/-16 and 53+/-20s with the value for U--M being shorter than for the other two conditions (P0.05). The V(O)(2) slow component was similar at both cadences, but iEMG only increased beyond minute 2 during high-intensity cycling at 115rpm. These results demonstrate that V(O)(2) kinetics are influenced by an interaction of exercise intensity and pedal rate and are consistent with the notion that changes in muscle fibre recruitment are responsible for slower phase II V(O)(2) kinetics during high-intensity and work-to-work exercise transitions.

We hypothesised that dichloroacetate (DCA) would reduce blood lactate accumulation, pulmonary carbon dioxide output (.V(CO2)) and ventilation (.V(E)) at sub-maximal work rates, and improve exercise tolerance during incremental exercise in healthy humans. Nine males (mean+/-SD, age 27+/-4 years) completed, in random order, two ramp incremental cycle ergometer tests to the limit of tolerance following the intravenous infusion of DCA (75 mg/kg body mass in 80 ml saline) or an equivalent volume of saline (as placebo). Relative to control, blood [lactate] was significantly reduced by DCA immediately before exercise (CON: 0.7+/-0.2 vs. DCA: 0.5+/-0.2mM; P

We investigated the pedal rate dependency of the effect of priming exercise on pulmonary oxygen uptake (V̇o2) kinetics. Seven healthy men completed two, 6-min bouts of high-intensity cycle exercise (separated by 6 min of rest) using different combinations of extreme pedal rates for the priming and criterion exercise bouts (i.e., 35→35, 35→115, 115→35, and 115→115 rev/min). Pulmonary gas exchange and heart rate were measured breath-by-breath, and muscle oxygenation was assessed using near-infrared spectroscopy. When the priming bout was performed at 35 rev/min (35→35 and 35→115 conditions), the phase II V̇o2time constant (τ) was not significantly altered ( bout 1: 31 ± 7 vs. bout 2: 30 ± 5 s and bout 1: 48 ± 16 vs. bout 2: 46 ± 21 s, respectively). However, when the priming bout was performed at 115 rev/min (115→35 and 115→115 conditions), the phase II τ was significantly reduced ( bout 1: 31 ± 7 vs. bout 2: 26 ± 5 s and bout 1: 48 ± 16 vs. bout 2: 39 ± 9 s, respectively, P < 0.05). Muscle oxygenation was significantly higher after priming exercise in all four conditions, but significant effects on V̇o2kinetics were only evident when muscle O2extraction (measured as Δ[deoxyhemoglobin]/ΔV̇o2) was elevated in the fundamental response phase. These data indicate that prior high-intensity exercise at a high pedal rate can speed V̇o2kinetics during subsequent high-intensity exercise, presumably through specific priming effects on type II muscle fibers.

It has been suggested that the slower O2 uptake (V̇o2) kinetics observed when exercise is initiated from an elevated baseline metabolic rate are linked to an impairment of muscle O2 delivery. We hypothesized that “priming” exercise would significantly reduce the phase II time constant (τ) during subsequent severe-intensity cycle exercise initiated from an elevated baseline metabolic rate. Seven healthy men completed exercise transitions to 70% of the difference between gas exchange threshold (GET) and peak V̇o2 from a moderate-intensity baseline (90% GET) on three occasions in each of the “unprimed” and “primed” conditions. Pulmonary gas exchange, heart rate, and the electromyogram of m. vastus lateralis were measured during all tests. The phase II V̇o2 kinetics were slower when severe exercise was initiated from a baseline of moderate exercise compared with unloaded pedaling (mean ± SD τ, 42 ± 15 vs. 33 ± 8 s; P < 0.05), but were not accelerated by priming exercise (42 ± 17 s; P > 0.05). The amplitude of the V̇o2 slow component and the change in electromyogram from minutes 2 to 6 were both significantly reduced following priming exercise (V̇o2 slow component: from 0.47 ± 0.09 to 0.27 ± 0.13 l/min; change in integrated electromyogram between 2 and 6 min: from 51 ± 35 to 26±43% of baseline; P < 0.05 for both comparisons). These results indicate that the slower phase II V̇o2 kinetics observed during transitions to severe exercise from an elevated baseline are not altered by priming exercise, but that the reduced V̇o2 slow component may be linked to changes in muscle fiber activation.

(31)Phosphate-magnetic resonance spectroscopy and near infrared spectroscopy (NIRS) were used for the simultaneous assessment of changes in quadriceps muscle metabolism and oxygenation during consecutive bouts of high-intensity exercise. Six male subjects completed two 6 min bouts of single-legged knee-extension exercise at 80% of the peak work rate separated by 6 min of rest while positioned inside the bore of a 1.5 T superconducting magnet. The total haemoglobin and oxyhaemoglobin concentrations in the area of the quadriceps muscle interrogated with NIRS were significantly higher in the baseline period prior to the second compared with the first exercise bout, consistent with an enhanced muscle oxygenation. Intramuscular phosphorylcreatine concentration ([PCr]) dynamics were not different over the fundamental region of the response (time constant for bout 1, 51 +/- 15 s versus bout 2, 52 +/- 17 s). However, the [PCr] dynamics over the entire response were faster in the second bout (mean response time for bout 1, 72 +/- 16 s versus bout 2, 57 +/- 8 s; P0.05), as a consequence of a greater fall in [PCr] in the fundamental phase and a reduction in the magnitude of the 'slow component' in [PCr] beyond 3 min of exercise (bout 1, 10 +/- 6% versus bout 2, 5 +/- 3%; P0.05). These data suggest that the increased muscle O(2) availability afforded by the performance of a prior bout of high-intensity exercise does not significantly alter the kinetics of [PCr] hydrolysis at the onset of a subsequent bout of high-intensity exercise. The greater fall in [PCr] over the fundamental phase of the response following prior high-intensity exercise indicates that residual fatigue acutely reduces muscle efficiency.