Tolerance to high-intensity constant-power (P) exercise is well described by a hyperbola with two parameters: a curvature constant (W') and power asymptote termed "critical power" (CP). Since the ability to sustain exercise is closely related to the ability to meet the ATP demand in a steady state, we reasoned that pulmonary O(2) uptake (Vo(2)) kinetics would relate to the P-tolerable duration (t(lim)) parameters. We hypothesized that 1) the fundamental time constant (τVo(2)) would relate inversely to CP; and 2) the slow-component magnitude (ΔVo(2sc)) would relate directly to W'. Fourteen healthy men performed cycle ergometry protocols to the limit of tolerance: 1) an incremental ramp test; 2) a series of constant-P tests to determine Vo(2max), CP, and W'; and 3) repeated constant-P tests (WR(6)) normalized to a 6 min t(lim) for τVo(2) and ΔVo(2sc) estimation. The WR(6) t(lim) averaged 365 ± 16 s, and Vo(2max) (4.18 ± 0.49 l/min) was achieved in every case. CP (range: 171-294 W) was inversely correlated with τVo(2) (18-38 s; R(2) = 0.90), and W' (12.8-29.9 kJ) was directly correlated with ΔVo(2sc) (0.42-0.96 l/min; R(2) = 0.76). These findings support the notions that 1) rapid Vo(2) adaptation at exercise onset allows a steady state to be achieved at higher work rates compared with when Vo(2) kinetics are slower; and 2) exercise exceeding this limit initiates a "fatigue cascade" linking W' to a progressive increase in the O(2) cost of power production (Vo(2sc)), which, if continued, results in attainment of Vo(2max) and exercise intolerance. Collectively, these data implicate Vo(2) kinetics as a key determinant of high-intensity exercise tolerance in humans.

The physiological equivalents of the curvature constant (W') of the high-intensity power-duration (P-t(LIM)) relationship are poorly understood, although they are presumed to reach maxima/minima at exhaustion. In an attempt to improve our understanding of the determinants of W', we therefore aimed to determine its recovery kinetics following exhaustive exercise (which depletes W') concomitantly with those of O(2) uptake (V(O(2)), a proxy for the kinetics of phosphocreatine replenishment) and blood lactate concentration ([L(-)]). Six men performed cycle-ergometer exercise to t(LIM): a ramp and four constant-load tests, at different work rates, for estimation of lactate threshold, W', critical power (CP), and maximum V(O(2)). Three further exhausting tests were performed at different work rates, each preceded by an exhausting "conditioning" bout, with intervening recoveries of 2, 6, and 15 min. Neither prior exhaustion nor recovery duration altered V(O(2)) or [L(-)] at t(LIM). Postconditioning, the P-t(LIM) relationship remained well characterized by a hyperbola, with CP unchanged. However, W' recovered to 37 +/- 5, 65 +/- 6, and 86 +/- 4% of control following 2, 6, and 15 min of intervening recovery, respectively. The W' recovery was curvilinear [interpolated half time (t(1/2)) = 234 +/- 32 s] and appreciably slower than V(O(2)) recovery (t(1/2) = 74 +/- 2 s) but faster than [L(-)] recovery (t(1/2) = 1,366 +/- 799 s). This suggests that W' determines supra-CP exercise tolerance, its restitution kinetics are not a unique function of phosphocreatine concentration or arterial [L(-)], and it is unlikely to simply reflect a finite energy store that becomes depleted at t(LIM).

Key pointsr Heavy-intensity exercise causes a progressive increase in energy demand that contributes to exercise limitation.r This inefficiency arises within the locomotor muscles and is thought to be due to an increase in the ATP cost of power production; however, the responsible mechanism is unresolved.r We measured whole-body O 2 uptake and skeletal muscle ATP turnover by combined pulmonary gas exchange and magnetic resonance spectroscopy during moderate and heavy exercise in humans.r Muscle ATP synthesis rate increased throughout constant-power heavy exercise, but this increase was unrelated to the progression of whole-body inefficiency.r Our data indicate that the increased ATP requirement is not the sole cause of inefficiency during heavy exercise, and other mechanisms, such as increased O 2 cost of ATP resynthesis, may contribute.Abstract During constant-power high-intensity exercise, the expected increase in oxygen uptake (V O 2 ) is supplemented by aV O 2 slow component (V O 2 sc ), reflecting reduced work efficiency, predominantly within the locomotor muscles. The intracellular source of inefficiency is postulated to be an increase in the ATP cost of power production (an increase in P/W). To test this hypothesis, we measured intramuscular ATP turnover with 31 P magnetic resonance spectroscopy (MRS) and whole-bodyV O 2 during moderate (MOD) and heavy (HVY) bilateral knee-extension exercise in healthy participants (n = 14). Unlocalized 31 P spectra were collected from the quadriceps throughout using a dual-tuned ( 1 H and 31 P) surface coil with a simple pulse-and-acquire sequence. Total ATP turnover rate (ATP tot ) was estimated at exercise cessation from direct measurements of the dynamics of phosphocreatine (PCr) and proton handling. Between 3 and 8 min during MOD, there was no discernableV O 2 sc (mean ± SD, 0.06 ± 0.12 l min −1 ) or change in [PCr] (30 ± 8 vs. 32 ± 7 mM) or ATP tot (24 ± 14 vs. 17 ± 14 mM min −1 ; each P = n.s.). During HVY, theV O 2 sc was 0.37 ± 0.16 l min −1 (22 ± 8%), [PCr] decreased (19 ± 7 vs. 18 ± 7 mM, or 12 ± 15%; P < 0.05) and ATP tot increased (38 ± 16 vs. 44 ± 14 mM min −1 , or 26 ± 30%; P < 0.05) between 3 and 8 min. However, the increase in ATP tot ( ATP tot ) was not correlated with theV O 2 sc during HVY (r 2 = 0.06; P = n.s.

Bowen TS, Cannon DT, Murgatroyd SR, Birch KM, Witte KK, Rossiter HB. The intramuscular contribution to the slow oxygen uptake kinetics during exercise in chronic heart failure is related to the severity of the condition. J Appl Physiol 112: 378 -387, 2012. First published October 27, 2011 doi:10.1152/japplphysiol.00779.2011The mechanism for slow pulmonary O2 uptake (V O2) kinetics in patients with chronic heart failure (CHF) is unclear but may be due to limitations in the intramuscular control of O2 utilization or O2 delivery. Recent evidence of a transient overshoot in microvascular deoxygenation supports the latter. Prior (or warm-up) exercise can increase O2 delivery in healthy individuals. We therefore aimed to determine whether prior exercise could increase muscle oxygenation and speed V O2 kinetics during exercise in CHF. Fifteen men with CHF (New York Heart Association I-III) due to left ventricular systolic dysfunction performed two 6-min moderate-intensity exercise transitions (bouts 1 and 2, separated by 6 min of rest) from rest to 90% of lactate threshold on a cycle ergometer. V O2 was measured using a turbine and a mass spectrometer, and muscle tissue oxygenation index (TOI) was determined by near-infrared spectroscopy. Prior exercise increased resting TOI by 5.3 Ϯ 2.4% (P ϭ 0.001), attenuated the deoxygenation overshoot (Ϫ3.9 Ϯ 3.6 vs. Ϫ2.0 Ϯ 1.4%, P ϭ 0.011), and speeded the V O2 time constant (V O2; 49 Ϯ 19 vs. 41 Ϯ 16 s, P ϭ 0.003). Resting TOI was correlated to V O2 before (R 2 ϭ 0.51, P ϭ 0.014) and after (R 2 ϭ 0.36, P ϭ 0.051) warm-up exercise. However, the mean response time of TOI was speeded between bouts in half of the patients (26 Ϯ 8 vs. 20 Ϯ 8 s) and slowed in the remainder (32 Ϯ 11 vs. 44 Ϯ 16 s), the latter group having worse New York Heart Association scores (P ϭ 0.042) and slower V O2 kinetics (P ϭ 0.001). These data indicate that prior moderate-intensity exercise improves muscle oxygenation and speeds V O2 kinetics in CHF. The most severely limited patients, however, appear to have an intramuscular pathology that limits V O2 kinetics during moderate exercise. muscle oxygenation; near-infrared spectroscopy; prior exercise CHRONIC HEART FAILURE (CHF) is a syndrome characterized by exercise intolerance due to breathlessness and fatigue in the presence of cardiac dysfunction. A treadmill or cycle-based symptom-limited peak exercise test, with pulmonary gas exchange measurement to determine peak O 2 uptake (V O 2peak ), is the most widely used measure of physiological limitation in CHF and provides objective information on aerobic capacity, symptomatology, and prognosis (35). However, activities of daily living rarely occur at or around V O 2peak . Therefore, the rate at which aerobic energy transfer adapts [O 2 uptake (V O 2 ) kinetics] to changing energy demands may provide an assessment that is more appropriate to daily exercise limitations in CHF than traditional measures (1, 52). Accordingly, initial evidence indicates that V O 2 kinetics are more strongly correlated to disease s...

Objective-Circulating progenitor cells (CPC) have emerged as potential mediators of vascular repair. In experimental models, CPC mobilization is critically dependent on nitric oxide (NO

During exercise below the lactate threshold (LT), the rate of adjustment (τ) of pulmonary O 2 uptake (V O 2 ) is slowed when initiated from a raised work rate. Whether this is consequent to the intrinsic properties of newly recruited muscle fibres, slowed circulatory dynamics or the effects of a raised metabolism is not clear. We aimed to determine the influence of these factors on τV O 2 using combined in vivo and in silico approaches. Fifteen healthy men performed repeated 6 min bouts on a cycle ergometer with work rates residing between 20 W and 90% LT, consisting of the following: (1) two step increments in work rate (S1 and S2), one followed immediately by the other, equally bisecting 20 W to 90% LT; (2) two 20 W to 90% LT bouts separated by 30 s at 20 W to raise muscle oxygenation and pretransition metabolism (R1 and R2); and (3) two 20 W to 90% LT bouts separated by 12 min at 20 W allowing full recovery (F1 and F2). Pulmonary O 2 uptake was measured breath by breath by mass spectrometry and turbinometry, and quadriceps oxygenation using near-infrared spectroscopy. The influence of circulatory dynamics on the coupling of muscle and lung τV O 2 was assessed by computer simulations. The τV O 2 in R2 (32 ± 9 s) was not different (P > 0.05) from S2 (30 ± 10 s), but both were greater (P < 0.05) than S1 (20 ± 10 s) and the F control bouts (26 ± 10 s). The slowedV O 2 kinetics in R2 occurred despite muscle oxygenation being raised throughout, and could not be explained by slowed circulatory dynamics (τV O 2 predicted by simulations: S1 = R2 < S2). These data therefore suggest that the dynamics of muscle O 2 consumption are slowed when exercise is initiated from a less favourable energetic state.

These data suggest that the key indices of aerobic function may be accurately and reliably estimated during a single exercise test. This test may provide a basis for simplifying assessment and prescription of exercise training and experimental interventions.

Phase 2 pulmonary oxygen uptake kinetics (ϕ2 τV̇o) reflect muscle oxygen consumption dynamics and are sensitive to changes in state of training or health. This study identified an unbiased method for data collection, handling, and fitting to optimize V̇o kinetics estimation. A validated computational model of V̇o kinetics and a Monte Carlo approach simulated 2 × 10 moderate-intensity transitions using a distribution of metabolic and circulatory parameters spanning normal health. Effects of averaging (interpolation, binning, stacking, or separate fitting of up to 10 transitions) and fitting procedures (biexponential fitting, or ϕ2 isolation by time removal, statistical, or derivative methods followed by monoexponential fitting) on accuracy and precision of V̇o kinetics estimation were assessed. The optimal strategy to maximize accuracy and precision of τV̇o estimation was 1-s interpolation of 4 bouts, ensemble averaged, with the first 20 s of exercise data removed. Contradictory to previous advice, we found optimal fitting procedures removed no more than 20 s of ϕ1 data. Averaging method was less critical: interpolation, binning, and stacking gave similar results, each with greater accuracy compared with analyzing repeated bouts separately. The optimal procedure resulted in ϕ2 τV̇o estimates for transitions from an unloaded or loaded baseline that averaged 1.97 ± 2.08 and 1.04 ± 2.30 s from true, but were within 2 s of true in only 47-62% of simulations. Optimized 95% confidence intervals for τV̇o ranged from 4.08 to 4.51 s, suggesting a minimally important difference of ~5 s to determine significant changes in τV̇o during interventional and comparative studies. We identified an unbiased method to maximize accuracy and precision of oxygen uptake kinetics (τV̇o) estimation. The optimum number of bouts to average was four; interpolation, bin, and stacking averaging methods gave similar results. Contradictory to previous advice, we found that optimal fitting procedures removed no more than 20 s of phase 1 data. Our data suggest a minimally important difference of ~5 s to determine significant changes in τV̇o during interventional and comparative studies.