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1Department of Exercise and Sport Science, Manchester Metropolitan University, Alsager ST7 2HL; and 2Department of Anaesthesia, Wythenshawe Hospital, Manchester M23 9LT, United Kingdom
Submitted 16 April 2003 ; accepted in final form 17 November 2003
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONREFERENCES |
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O2) by nitric oxide and result in a speeding of phase II pulmonary O2 kinetics at the onset of heavy-intensity exercise. Seven men performed square-wave transitions from unloaded cycling to a work rate requiring 40% of the difference between the gas exchange threshold and peak O2 with and without prior intravenous infusion of L-NAME (4 mg/kg in 50 ml saline over 60 min). Pulmonary gas exchange was measured breath by breath, and O2 kinetics were determined from the averaged response to two exercise bouts performed in each condition. There were no significant differences between the control (C) and L-NAME conditions (L) for baseline O2, the duration of phase I, or the amplitude of the primary O2 response. However, the time constant of the O2 response in phase II was significantly smaller (mean ± SE: C: 25.1 ± 3.0 s; L: 21.8 ± 3.3 s; P < 0.05), and the amplitude of the O2 slow component was significantly greater (C: 240 ± 47 ml/min; L: 363 ± 24 ml/min; P < 0.05) after L-NAME infusion. These data indicate that inhibition of NOS by L-NAME results in a significant (13%) speeding of O2 kinetics and a significant increase in the amplitude of the O2 slow component in the transition to heavy-intensity cycle exercise in men. The speeding of the primary component O2 kinetics after L-NAME infusion indicates that at least part of the intrinsic inertia to oxidative metabolism at the onset of heavy-intensity exercise may result from inhibition of mitochondrial O2 by nitric oxide. The cause of the larger O2 slow-component amplitude with L-NAME requires further investigation but may be related to differences in muscle blood flow early in the rest-to-exercise transition. respiratory; gas exchange
O2) rises to meet the increased energetic requirement. Within the moderate-exercise-intensity domain (i.e., exercise that does not cause a significant accumulation of muscle or blood lactate), there is evidence that the kinetic adjustment of O2 is limited by the rate with which mitochondria adjust oxidative ATP supply to meet demand (19, 23, 51, 53). The precise locus of this metabolic inertia, however, remains to be established. For work rates that elicit a sustained lactic acidosis (i.e., heavy-intensity exercise), there is debate over whether the O2 dynamics are additionally limited by the rate with which O2 is delivered to working muscle (19, 21, 50, 51).
Nitric oxide (NO), which is released in large quantities at the onset of exercise (1), has been implicated in a wide array of physiological functions, including the regulation of vasodilatation (28). NO synthase (NOS), the enzyme responsible for synthesis of NO, is located within the skeletal muscle vascular endothelium as well as within myocytes (17). NOS may be inhibited with L-arginine analogs such as NG-nitro-L-arginine methyl ester (L-NAME) (16), such that the release of NO is markedly attenuated. Although it remains unclear what effect, if any, NO has on O2 during exercise in humans, it has been demonstrated, in vitro, that NO may reversibly inhibit mitochondrial respiration by binding to the O2-binding site at cytochrome-c oxidase in the electron transport chain (8, 9, 13, 46). It is, therefore, possible that this may be one of the loci for the metabolic inertia after the onset of exercise. Recently, Kindig et al. reported that infusion of L-NAME before exercise caused an 
30% speeding of the time constant of the primary O2 response to both moderate- (32) and heavy-intensity (31) treadmill running in the Thoroughbred horse, with no change in the steady-state O2. We have also shown that L-NAME infusion causes a significant speeding of the primary O2 kinetics after the onset of moderate-intensity exercise in humans (27). Whether L-NAME similarly influences the rate at which O2 adjusts in humans after the onset of heavy-intensity exercise, where O2 availability may provide an additional limitation to O2 kinetics (19, 21, 50, 51), remains to be established.
Heavy-intensity exercise is associated with the development of a O2 "slow component" that emerges 2 min after the onset of exercise and causes O2 to rise above the expected steady-state value (52). Kindig et al. (31) reported that infusion of L-NAME resulted in a significant reduction in the time at which the O2 slow component emerged (from 125 to 65 s) and an increased amplitude of the response (from 4.5 to 5.3 l/min; P = not significant) in five geldings. It is not known whether L-NAME infusion similarly affects the parameters of the O2 slow component during heavy-intensity exercise in humans.
Therefore, in the present study, we investigated the effect of L-NAME infusion on the primary and slow components of pulmonary O2 kinetics after the onset of heavy-intensity exercise in men. We hypothesized that NOS inhibition by L-NAME would lead to a significant speeding of the primary component O2 kinetics and a significant increase in the amplitude of the O2 slow component.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Procedures. The participants were required to visit the laboratory on five occasions. On the first visit, the participants completed an incremental exercise test to exhaustion on an electronically braked cycle ergometer (Jaeger Ergoline E800, Mindjhaart, The Netherlands). After 3 min of unloaded cycling, work rate was increased by 5 W every 10 s (i.e., 30 W/min) until the participant was unable to continue. The participants cycled at a self-selected pedal rate (60–90 rpm), and this pedal rate and the saddle and handlebar height and configuration were recorded and reproduced in subsequent tests. Pulmonary gas exchange was measured on a breath-by-breath basis (see below). The peak O2 was determined as the highest value recorded in any 30-s period before the participant's volitional termination of the test. The gas exchange threshold was determined as the first disproportionate increase in CO2 output from visual inspection of individual plots of CO2 output vs. O2 by an experienced reviewer, and the work rate that would require 40% of the difference between the O2 at gas exchange threshold and the peak O2 (40% 
) was calculated.
Our protocol for the L-NAME infusion was based on that described by Frandsen et al. (16) who demonstrated that this infusion protocol resulted in a 67% reduction in NOS activity in skeletal muscle. A cannula was placed in a hand vein, and participants rested for a 20-min period before L-NAME (Merck Biosciences AG, Nottingham, UK; 4 mg/kg body mass in 50 ml of saline) was infused over 60 min. Throughout the infusion, blood pressure and heart rate were monitored. After a 60-min rest, the participants performed an exercise bout at 40% for 6 min. This procedure was completed four times in total: twice with and twice without L-NAME infusion. The participants did not know whether they were being infused with L-NAME or with saline. The conditions were presented in random order on different days separated by at least 72 h. The participants, therefore, performed two bouts of heavy-intensity exercise in each condition.
The square-wave exercise protocol began with 3 min of baseline pedalling at 20 W (the lowest available work rate on the cycle ergometer), followed by an abrupt transition to the 40% work rate for 6 min. Pulmonary gas exchange was measured breath by breath, and heart rate was monitored by short-range telemetry (Polar Electro Oy, Kempele, Finland) throughout all exercise tests. The participants wore a nose clip and breathed through a low dead space, low-resistance mouthpiece and volume sensor assembly. Pulmonary gas exchange was measured with a mass spectrometer and volume turbine system (Morgan EX670, Morgan Medical, Gillingham, Kent). The system was calibrated before each test by using gases of known concentration and a precision 3-liter calibration syringe. A fingertip blood sample was collected into a capillary tube immediately before and after one of the exercise bouts in each condition and subsequently analyzed for blood lactate concentration (YSI 1500 Sport lactate analyzer, Yellow Springs Instruments).
Analysis of O2 kinetics. The breath-by-breath O2 data for each transition were interpolated to give second-by-second values and time aligned to the start of exercise. For each participant and each condition, the repeat transitions were then averaged to enhance the underlying response characteristics. The baseline O2 was defined as the average O2 measured during unloaded cycling between 160 and 20 s before the start of exercise. The cardiodynamic component (phase I) was ignored by eliminating the first 20 s of data after the onset of exercise. Subsequently, nonlinear regression techniques were used to fit the remaining O2 data with the following equation
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), and delay times (TD) for the primary (p) and slow (s) components of the response. An iterative process was used to minimize the sum of squared error between the fitted function and the observed values. Where a O2 slow-component term was not evident, the second term dropped out.
To provide an indication of the overall rate of O2 adaptation in the primary phase of the response, the mean response time (MRTp = TDp + p) was also calculated. Also, to provide an index of the magnitude of the O2 slow component that was independent of the modeling procedure, we determined the increase in O2 from 2 to 6 min of exercise [O2(6–2)].
Statistics. Paired t-tests were used to test for significant differences in the O2 kinetic parameters between the control and L-NAME conditions with significance declared when P < 0.05. Results are reported as means ± SE, unless otherwise indicated.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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O2 was 49.4 ± 5.6 ml·kg-1·min-1 with gas exchange threshold occurring at 51 ± 8% peak O2. The increase in work rate above baseline cycling (20 W) to 40% was 227 ± 10 W. As would be expected for exercise in the heavy-intensity domain, blood lactate concentration rose significantly above preexercise values, in both the control and L-NAME conditions (change in lactate concentration, control: 2.9 ± 0.3 mM; L-NAME: 3.2 ± 0.3 mM; P = not significant). At rest during the L-NAME infusion, blood pressure was significantly higher and heart rate significantly lower compared with the control condition (P < 0.05). Compared with control, heart rate was lower after L-NAME infusion during unloaded cycling (control: 88 ± 4 beats/min; L-NAME: 74 ± 2 beats/min; P < 0.01), but this difference was not significant at the end of exercise (control: 151 ± 4 beats/min; L-NAME: 146 ± 2 beats/min).
The O2 kinetic response data are presented in Table 1, and the response of a representative participant is shown in Fig. 1. Infusion of L-NAME did not significantly affect baseline O2, the primary component amplitude, or the primary component time delay. However, L-NAME infusion resulted in a 13% speeding of the O2 kinetic response (p reduced from 25.1 ± 3.0 to 21.8 ± 3.3 s; P < 0.05). The mean response time (TDp + p) of the primary response was also significantly reduced (control: 38.3 ± 2.4; L-NAME: 35.0 ± 2.8 s; P < 0.05).
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A O2 slow component was evident in five of the seven participants in the control condition and in the same five participants in the L-NAME condition. However, in the remaining two participants, the data were well fit by a monoexponential function with delay, despite the work rate being ostensibly in the heavy domain (change in lactate concentration of 2–3 mM). The time at which the O2 slow component emerged was not different between the L-NAME and control conditions, but the amplitude of the O2 slow component was 50% greater after L-NAME infusion (control: 240 ± 47 ml/min; L-NAME: 363 ± 24 ml/min; P < 0.05; Table 1). The magnitude of the O2 slow component calculated as O2(6–2) was also significantly greater with L-NAME (control: 185 ± 35 ml/min; L-NAME: 238 ± 49 ml/min; P < 0.05).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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O2 kinetic response in phase II and a significantly increased amplitude of the O2 slow component after the transition to a work rate within the heavy-intensity exercise domain.
O2 primary component. Infusion of L-NAME resulted in a significant speeding of the primary component O2 kinetics. These results extend our earlier report that infusion of L-NAME resulted in a significant speeding of the primary component O2 kinetics after the onset of moderate-intensity exercise (27). Our results are also consistent with the studies of Kindig et al. (31, 32), which demonstrated a 30% speeding of the primary component O2 kinetics during both moderate- and heavy-intensity treadmill running in the Thoroughbred horse. It is possible that the greater effect observed in the horse (31, 32) compared with men (Ref. 27 and present study) is related to the differences in the dose of L-NAME administered (4 mg/kg in men compared with 20 mg/kg in the horse). Collectively, these studies indicate that inhibition of NOS may remove some of the inertia to mitochondrial respiration and allow an acceleration of O2 kinetics in the transition to a higher work rate within both the moderate- and heavy-intensity exercise domains.
The procedure we used in the present study for L-NAME infusion (4 mg/kg body mass infused over 60 min) has been shown to result in a 67 ± 8% reduction in muscle NOS activity in humans (16). We, therefore, postulate that the speeding of O2 kinetics with L-NAME resulted from a reduction of NO-mediated inhibition of mitochondrial O2. Direct evidence of a role for NO in regulating muscle O2 in the transition to exercise in humans is presently limited, partly because the studies conducted to date have generally focused on measuring O2 in the steady state of exercise (6, 16). However, Radegran and Saltin (41) could detect no significant effect of NOS inhibition (with L-NMMA) on leg O2 either 1 or 3 min after the onset of exercise. Possible explanations for the difference between our study and that of Radegran and Saltin (41) include differences in the potency of the NOS inhibitor that was employed [L-NAME vs. NG-monomethyl-L-arginine (L-NMMA)], the exercise modality and intensity, and the time over which O2 was measured. (Pulmonary O2 was measured continuously in our study to enable the calculation of the time constant of the response, whereas in Radegran and Saltin's study, absolute muscle O2 was measured at discrete points in time.)
In vitro studies indicate that NO might influence mitochondrial function by several possible mechanisms. NO and its derivatives (reactive nitrogen species) are believed to inhibit a number of enzymes that are involved in energy transduction, including creatine kinase, glyceraldehyde-3-phosphate dehydrogenase, and aconitase (29, 54), as well as respiratory complexes I–IV (7, 12). Furthermore, there is strong evidence that NO regulates mitochondrial function by inhibiting cytochrome-c oxidase, the terminal enzyme in the electron transport chain, by competing with O2 for the binding site of cytochrome-c oxidase (8, 46). It was not the purpose of the present study to pinpoint the exact mechanism(s) by which L-NAME facilitated a speeding of the pulmonary (and, by inference, muscle) O2 kinetics. Future studies should seek to identify the site(s) at which NO potentially exerts an inhibitory effect on mitochondrial respiration in the transition from rest to exercise in humans.
Although the O2 adaptation to exercise was faster in the L-NAME compared with the control condition, the amplitude of the primary O2 responses above baseline (Ap) was not different. This finding is consistent with other studies that have infused NOS inhibitors before exercise in humans (16, 41) and horses (32, 37). For example, in the study of Frandsen et al. (16), leg O2 was not significantly different between the L-NAME and control conditions at either 10 or 20 min of submaximal exercise. In horses, the primary component O2 amplitude was unaltered by L-NAME, despite significantly faster O2 kinetics (31, 32). It, therefore, appears that the inhibitory effect of NO on muscle O2 might only be evident in the rest-to-exercise transition; regulation of muscle blood flow and O2 extraction ultimately enable the same primary component O2 to be attained. Indeed, if it is reasonably assumed that L-NAME does not influence either muscle effi-ciency or the ATP turnover rate required at rest and at the same submaximal work rate, then no change in the steady-state O2 would be expected. However, the large increase in NO release at exercise onset (which is hypothesized to retard mitochondrial flux) is presumably attenuated with L-NAME such that O2 extraction is increased and O2 rises at a faster rate to attain the steady-state requirement.
It should be pointed out that, although L-NAME infusion caused a significant speeding of the primary component O2 kinetics in the present study, NO inhibition of mitochondrial O2 can only account for a relatively small (13% on average) proportion of the lag in the O2 response after a transition to heavy-intensity exercise in humans. The location of the other limitations to O2 kinetics during heavy-intensity exercise, therefore, remain to be firmly established. Significant research attention has been directed to the possible role of pyruvate dehydrogenase complex activation and/or the availability of acetyl groups in limiting mitochondrial ATP production at exercise onset (26, 49). These studies reported that prior activation of the pyruvate dehydrogenase complex by infusion of dichloroacetate resulted in a marked attenuation of substrate-level phosphorylation, presumably due to an increased mitochondrial ATP production. However, a number of recent studies have reported no effect of dichloroacetate on muscle or pulmonary O2 kinetics during muscle contraction at 65% peak O2 in dogs (20), during upright cycle exercise (26a) or prone quadriceps exercise (44) at 70% peak O2 in humans (44), or during knee extension exercise at 110% peak O2 in humans (2). It has also been suggested that O2 availability influences the primary O2 kinetics during heavy exercise (50). However, although O2 availability may indeed provide an additional limitation to O2 kinetics at the onset of perimaximal exercise (21), there is no compelling evidence that increasing O2 delivery to muscle speeds the primary component O2 kinetics after the onset of heavy-intensity exercise (70–90% peak O2) in young, healthy participants performing upright cycle exercise (10, 11, 34, 35). It should also be stressed that oxidative phosphorylation may be under feedback control through one or more of the products of high-energy phosphate hydrolysis. Several studies have demonstrated tight coupling between phosphocreatine concentration kinetics and O2 kinetics after the onset of exercise (36, 43). Intriguingly, it has recently been demonstrated that phosphocreatine concentration kinetics are significantly faster in creatine kinase knockout mice, with the inference that oxidative phosphorylation is more rapidly activated (42). In this regard, it is of interest that NO has been reported to inhibit creatine kinase (29); removal of this inhibition after L-NAME administration may, therefore, provide one explanation for the faster primary component O2 kinetics observed in the present study.
O2 slow component. Another interesting finding in our study was the significantly greater amplitude of the O2 slow component after infusion of L-NAME. In the only other study that has examined the influence of NOS inhibition on pulmonary O2 kinetics during heavy-intensity exercise, Kindig et al. (31) reported that, compared with the control condition, L-NAME infusion resulted in an earlier emergence (from 125 to 65 s) and greater amplitude (from 4.5 to 5.3 l/min; P = not significant) of the O2 slow component in five geldings. In the same two of our seven participants for both conditions, the data were better fit with a monoexponential function with delay, despite the fact that the work rate was indeed heavy, as evidenced by the blood lactate concentration values that were elicited (2–3 mM above baseline). However, it is clear from the O2(6–2) data that the rate of increase of O2 over the last 4 min of the exercise bouts was greater after L-NAME infusion.
The reason for the significantly greater O2 slow component with L-NAME is unclear. There is evidence that the slow component is related to the increased recruitment of type II muscle fibers at high exercise intensities (4, 39, 40). However, it is evident that experimental manipulations that are expected to increase muscle blood flow and/or O2 availability [e.g., performance of prior heavy exercise (10, 18, 34); inspiration of a hyperoxic gas mixture (35)] attenuate the O2 slow-component amplitude. On the other hand, experimental interventions designed to reduce muscle blood flow and/or O2 availability do not consistently increase the O2 slow-component amplitude. For example, the slow-component amplitude is reduced in supine compared with upright cycle exercise (33) but is unaffected by the inspiration of hypoxic compared with normoxic gas (15). It is uncertain whether the changes in the slow component in these situations arise from differences in O2 availability, per se, or from possible changes in muscle fiber recruitment patterns as a consequence of the differences in O2 availability (4, 10, 39). In terms of explaining the greater slow-component amplitude with L-NAME, the possible effects of the drug on muscle blood flow in the transition to exercise, therefore, requires consideration.
NO activates soluble guanylate cyclase in vascular smooth muscle, resulting in vascular relaxation and increased tissue blood flow (38). In a number of species, there is evidence that cardiac output and/or muscle blood flow are reduced during exercise, and that O2 extraction at the muscle is correspondingly increased after NOS inhibition (25, 30, 45). In humans, muscle blood flow is typically lower at rest and in recovery from exercise with NOS inhibition (16, 41, 47). In contrast, it has generally (6, 16, 41), although not always (14, 25), been reported that skeletal muscle blood flow is unchanged after NOS inhibition during steady-state submaximal exercise. Hillig et al. (24) have recently reported that L-NMMA, when coinfused with sulfaphenazole to inhibit cytochrome P-450 2C9, causes a significant reduction in both muscle blood flow and steady-state O2, suggesting that an interaction between NOS and cytochrome P-450 2C9 preserves muscle blood flow when NOS is inhibited. It is unclear whether muscle blood flow is reduced in the rest-to-exercise transition after NOS inhibition in men because few studies have investigated the issue with sufficient temporal resolution to provide a definitive answer. However, Shoemaker et al. (47) reported that the magnitude and rate of adaptation of blood flow at the onset of forearm exercise were unaffected by infusion of atropine and L-NMMA, although the reduced blood flow observed at rest was maintained throughout the transition to exercise. Radegran and Saltin (41) also reported no effect of L-NMMA on muscle blood flow in the transition to exercise, although, unusually, the drug had no significant cardiovascular effects either. In the present study, heart rate during the unloaded cycling period before exercise was, on average, 14 beats/min lower after L-NAME infusion, and it is possible that this reflected a lower muscle blood flow with greater O2 extraction at the muscle to maintain O2 (16, 41, 47). It has been suggested that a reduced vascular conductance at rest (as would occur with NOS inhibition) could influence the effectiveness of the muscle pump at exercise onset (48). At present, in the absence of direct measures of muscle blood flow, we can only speculate that the greater O2 slow component with L-NAME might have been caused by a transient reduction in muscle blood flow and O2 delivery to working muscle in the early phase of the transition from rest to exercise. Alternatively, it is possible that there are changes in regional muscle O2 blood flow (
O2) with L-NAME, despite there being no change in bulk muscle blood flow (16, 41). Related to this, Radegran and Saltin (41) have suggested that a reduced O2 in some fibers resulting from reduced blood flow in adjacent capillaries may be compensated for by an increased O2 in other fibers. It is feasible that changes in regional muscle O2/O2 with L-NAME could alter muscle fiber recruitment patterns. Clearly, further studies are required to test this hypothesis.
Alternative explanations. At face value, it may seem paradoxical for an intervention to result in both a speeding of the primary component O2 kinetics and an increased amplitude of the O2 slow component during heavy exercise when both may be influenced by O2 availability (21, 33, 35). However, studies have demonstrated that the primary component O2 response is not speeded by interventions designed to improve muscle O2 availability (10, 19, 34, 35) and that muscle O2 availability is adequate or in excess of requirements, at least in the first 20 s of the transition to a higher metabolic rate (3, 22, 23, 53). It is, therefore, possible that a small reduction in muscle O2 delivery might not substantially impact the phase II time constant, at least at the exercise intensity that we studied (i.e., 40% or 70% peak O2). Alternatively, it is possible that the speeding of the primary component O2 kinetics that we observed with L-NAME may have been even more pronounced if muscle O2 delivery had been preserved at control values. However, without muscle blood flow data, we are presently unable to distinguish between these possibilities.
Pulmonary O2 kinetics represent a conflation of muscle O2 kinetics and the dynamic characteristics of cardiac output and venous volume. As discussed in our laboratory's previous study (27), possible alterations in muscle blood flow and/or its distribution with L-NAME, therefore, have the potential to distort the relationship between muscle and pulmonary O2 kinetics. Using a mathematical modeling approach, Barstow et al. (5) predicted that slower cardiac output kinetics (for the same muscle O2 kinetics) would result in a lengthening of phase I and apparently faster phase II pulmonary O2 kinetics. Assuming that L-NAME did indeed cause a transient reduction in muscle blood flow or its distribution during the on-transient, it is, therefore, possible that this could result in both the expression of faster phase II O2 kinetics at the lung (despite there being no change in muscle O2 kinetics) and the development of a greater O2 slow component. However, we could discriminate no difference in the duration of phase I with L-NAME in the present study, and we consider it unlikely that bulk muscle blood flow was reduced sufficiently or for long enough with L-NAME to result in a significant "distortional" speeding of the phase II O2 kinetics. This does not, however, rule out the possibility of altered muscle O2/O2 with L-NAME. Further studies are required to directly assess the influence of L-NAME on muscle O2, blood flow, and motor unit recruitment patterns in the transition to heavy-intensity exercise.
In conclusion, we have shown that inhibition of NOS by L-NAME resulted in a significant speeding of the primary component of pulmonary O2 kinetics in the transition to heavy-intensity cycle exercise. These data, in keeping with a previous study of Kindig et al. (31) in the horse, indicate that inhibition of mitochondrial O2 by NO contributes, in part, to the inertia in oxidative metabolism at the onset of heavy-intensity exercise. The cause of the greater O2 slow-component amplitude after L-NAME infusion remains to be determined with certainty but might be related to a transient reduction or greater heterogeneity of muscle blood flow and thus O2 availability in the rest-to-exercise transition.
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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O2 kinetics during the on-transient of heavy exercise are related to changes in muscle activity. J Appl Physiol 93: 167-174, 2002.O2 on-kinetics in isolated in situ canine muscle. J Appl Physiol 85: 1394-1403, 1998.O2 on-kinetics in canine muscle contracting at peak O2. J Appl Physiol 89: 1293-1301, 2000.O2 kinetics following the onset of heavy intensity cycle exercise. Pflügers Arch. In press.
O2 kinetics in the transition to moderate intensity exercise in man. J Physiol 552: 265-272, 2003.O2 during high-intensity cycling exercise is situated at the additional slow component. Int J Sports Med 22: 21-26, 2001.[CrossRef][Web of Science][Medline]
O2 kinetics in heavy submaximal exercise by hyperoxia and prior high-intensity exercise. J Appl Physiol 83: 1318-1325, 1997.O2 and intramuscular 31P metabolite kinetics during high-intensity exercise in humans. J Appl Physiol 95: 1105-1115, 2003.This article has been cited by other articles:
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) and in control conditions (
) in a representative participant. Notice the faster adjustment of