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