During high-intensity submaximal exercise, muscle fatigue and decreased efficiency are intertwined closely, and each contributes to exercise intolerance. Fatigue and muscle inefficiency share common mechanisms, for example, decreased "metabolic stability," muscle metabolite accumulation, decreased free energy of adenosine triphosphate breakdown, limited O2 or substrate availability, increased glycolysis, pH disturbance, increased muscle temperature, reactive oxygen species production, and altered motor unit recruitment patterns.

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1. A slow component to pulmonary oxygen uptake (V02) is reported during prolonged high power exercise performed at constant power output at, or above, approximately 60 % of the maximal oxygen uptake. The magnitude of the slow component is reported to be associated with the intensity of exercise and to be largely accounted for by an increased V0, across the exercising legs.2. On the assumption that the control mechanism responsible for the increased V02 is intensity dependent we hypothesized that it should also be apparent in multi-stage incremental exercise tests with the result that the V102-power output relationship would be curvilinear.3. We further hypothesized that the change in the 102-power output relationship could be related to the hierarchical recruitment of different muscle fibre types with a lower mechanical efficiency. 4. Six subjects each performed five incremental exercise tests, at pedalling rates of 40, 60, 80, 100 and 120 rev min-1, over which range we expected to vary the proportional contribution of different fibre types to the power output. Pulmonary V02 was determined continuously and arterialized capillary blood was sampled and analysed for blood lactate concentration ([lactate]b). 5. Below the level at which a sustained increase in [lactate]b was observed pulmonary V02 showed a linear relationship with power output; at high power outputs, however, there was an additional increase in V02 above that expected from the extrapolation of that linear relationship, leading to a positive curvilinear V02-power output relationship.6. No systematic effect on the magnitude or onset of the 'extra' VO2 was found in relation to pedalling rate, which suggests that it is recruitment in any simple way.

The "slow component" of O2 uptake (VO2) kinetics during constant-load heavy-intensity exercise is traditionally thought to derive from a progressive recruitment of muscle fibers. In this study, which represents a reanalysis of data taken from a previous study by our group (Grassi B, Hogan MC, Greenhaff PL, Hamann JJ, Kelley KM, Aschenbach WG, Constantin-Teodosiu D, Gladden LB. J Physiol 538: 195-207, 2002) we evaluated the presence of a slow component-like response in the isolated dog gastrocnemius in situ (n=6) during 4 min of contractions at approximately 60-70% of peak VO2. In this preparation all muscle fibers are maximally activated by electrical stimulation from the beginning of the contraction period, and no progressive recruitment of fibers is possible. Muscle VO2 was calculated as blood flow multiplied by arteriovenous O2 content difference. The muscle fatigued (force decreased by approximately 20-25%) during contractions. Kinetics of adjustment were evaluated for 1) VO2, uncorrected for force development; 2) VO2 normalized for peak force; 3) VO2 normalized for force-time integral. A slow component-like response, described in only one muscle out of six when uncorrected VO2 was considered, was observed in all muscles when VO2/peak force and VO2/force-time were considered. The amplitude of the slow component-like response, expressed as a fraction of the total response, was higher for VO2/peak force (0.18+/-0.06, means+/-SE) and for VO2/force-time (0.22+/-0.05) compared with uncorrected VO2 (0.04+/-0.04). A progressive recruitment of muscle fibers may not be necessary for the development of the slow component of VO2 kinetics, which may be caused by the metabolic factors that induce muscle fatigue and, as a consequence, reduce the efficiency of muscle contractions.

Using a computer model of oxidative phosphorylation developed previously [Korzeniewski and Mazat (1996) Biochem. J. 319, 143-148; Korzeniewski and Zoladz (2001) Biophys. Chem. 92, 17-34], we analyse the effect of several factors on the oxygen-uptake kinetics, especially on the oxygen consumption rate (VO2) and half-transition time t(1/2), at the onset of exercise in skeletal muscles. Computer simulations demonstrate that an increase in the total creatine pool [PCr+/-Cr] (where Cr stands for creatine and PCr for phosphocreatine) and in glycolytic ATP supply lengthen the half-transition time, whereas increase in mitochondrial content, in parallel activation of ATP supply and ATP usage, in oxygen concentration, in proton leak, in resting energy demand, in resting cytosolic pH and in initial alkalization decrease this parameter. Theoretical studies show that a decrease in the activity of creatine kinase (CK) [displacement of this enzyme from equilibrium during on-transient (rest-to-work transition)] accelerates the first stage of the VO2 on-transient, but slows down the second stage of this transient. It is also demonstrated that a prior exercise terminated a few minutes before the principal exercise shortens the transition time. Finally, it is shown that at a given ATP demand, and under conditions where CK works near the thermodynamic equilibrium, the half-transition time of VO2 kinetics is determined by the amount of PCr that has to be transformed into Cr during rest-to-work transition; therefore any factor that diminishes the difference in [PCr] between rest and work at a given energy demand will accelerate the VO2 on-kinetics. Our conclusions agree with the general idea formulated originally by Easterby [(1981) Biochem. J. 199, 155-161] that changes in metabolite concentrations determine the transition times between different steady states in metabolic systems.

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A group of 12 healthy non-smoking men [mean age 22.3 (SD 1.1) years], performed an incremental exercise test. The test started at 30 W, followed by increases in power output (P) of 30 W every 3 min, until exhaustion. Blood samples were taken from an antecubital vein for determination of plasma concentration lactate [La-]pl and acid-base balance variables. Below the lactate threshold (LT) defined in this study as the highest P above which a sustained increase in [La-]pl was observed (at least 0.5 mmol x l[-1] within 3 min), the pulmonary oxygen uptake (VO2) measured breath-by-breath, showed a linear relationship with P. However, at P above LT [in this study 135 (SD 30) W] there was an additional accumulating increase in VO2 above that expected from the increase in P alone. The magnitude of this effect was illustrated by the difference in the final P observed at maximal oxygen uptake (VO2max) during the incremental exercise test (Pmax,obs at VO2max) and the expected power output at VO2max(Pmax,exp at VO2max) predicted from the linear VO2-P relationship derived from the data collected below LT. The Pmax,obs at VO2max amounting to 270 (SD 19) W was 65.1 (SD 35) W (19%) lower (P < 0.01) than the Pmax,exp at VO2max. The mean value of VO2max reached at Pmax,obs amounted to 3555 (SD 226) ml x min(-1) which was 572 (SD 269) ml x min(-1) higher (P < 0.01) than the VO2 expected at this P, calculated from the linear relationship between VO2 and P derived from the data collected below LT. This fall in locomotory efficiency expressed by the additional increase in VO2, amounting to 572 (SD 269) ml O2 x min(-1), was accompanied by a significant increase in [La-]pl amounting to 7.04 (SD 2.2) mmol x l(-1), a significant increase in blood hydrogen ion concentration ([H+]b) to 7.4 (SD 3) nmol x l(-1) and a significant fall in blood bicarbonate concentration to 5.78 (SD 1.7) mmol x l(-1), in relation to the values measured at the P of the LT. We also correlated the individual values of the additional VO2 with the increases (delta) in variables [La-]pl and delta[H+]b. The delta values for [La-]pl and delta[H+]b were expressed as the differences between values reached at the Pmax,obs at VO2max and the values at LT. No significant correlations between the additional VO2 and delta[La-]pl on [H+]b were found. In conclusion, when performing an incremental exercise test, exceeding P corresponding to LT was accompanied by a significant additional increase in VO2 above that expected from the linear relationship between VO2 and P occurring at lower P. However, the magnitude of the additional increase in VO2 did not correlate with the magnitude of the increases in [La-]pl and [H+]b reached in the final stages of the incremental test.

New Findings r What is the central question of this study?A few weeks of endurance training accelerate the oxygen uptake (V O 2 ) on-kinetics in humans. The main aim of the present study was to determine whether the acceleration ofV O 2 onkinetics obtained by a short period of moderate-intensity training can be explained by an intensification of mitochondrial biogenesis. r What is the main finding and its importance?We demonstrated that 5 weeks of moderate-intensity training accelerates theV O 2 on-kinetics during moderate-intensity cycling in the absence of enhanced mitochondrial biogenesis or capillarization in the trained muscles. We postulate that in the early stages of training an intensification of 'parallel activation' of oxidative phosphorylation could account for the shortening of theV O 2 on-transient.The effects of 5 weeks of moderate-intensity endurance training on pulmonary oxygen uptake kinetics (V O 2 on-kinetics) were studied in 15 healthy men (mean ± SD: age 22.7 ± 1.8 years, body weight 76.4 ± 8.9 kg and maximalV O 2 46.0 ± 3.7 ml kg −1 min −1 ). Training caused a significant acceleration (P = 0.003) ofV O 2 on-kinetics during moderate-intensity cycling (time constant of the 'primary' component 30.0 ± 6.6 versus 22.8 ± 5.6 s before and after training, respectively) and a significant decrease (P = 0.04) in the amplitude of the primary component (837 ± 351 versus 801 ± 330 ml min −1 ). No changes in myosin heavy chain distribution, muscle fibre capillarization, level of peroxisome proliferator-activated receptor γ coactivator 1α and other markers of mitochondrial biogenesis (mitochondrial DNA copy number, cytochrome c and cytochrome oxidase subunit I contents) in the vastus lateralis were found after training. A significant downregulation in the content of the sarcoplasmic reticulum ATPase 2 (SERCA2; P = 0.03) and a tendency towards a decrease in SERCA1 (P = 0.055) was found after training. The decrease in SERCA1 was positively correlated (P = 0.05) with the training-induced decrease in the gain of theV O 2 on-kinetics ( V O 2 at steady state/ power output). In the early stage of training, the acceleration inV O 2 on-kinetics during moderate-intensity cycling can occur without enhanced mitochondrial biogenesis or changes in muscle myosin heavy chain distribution and