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Canadian Centre for 1 Activity and Aging2 School of Kinesiology3 Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada
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Abstract |
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(Received 4 November 2003;
accepted after revision 25 February 2004; first published online 16 March 2004)
Corresponding author D. H. Paterson: Canadian Centre for Activity and Aging, School of Kinesiology, The University of Western Ontario, London, Ontario, Canada N6A 3K7. Email: dpaterso{at}uwo.ca
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Introduction |
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The breathing of hypoxic gas mixtures (decreased O2 content) presents a challenge to both O2 delivery and utilization pathways. Previous studies (Rowell et al. 1986; Koskolou et al. 1997) reported that in the steady-state of submaximal exercise, increases in cardiac output and limb blood flow compensate for reduced O2 availability in hypoxia, and muscle O2 consumption is maintained at normoxic values by compensatory responses which ensure that muscle O2 delivery is maintained without a reliance on increased O2 extraction and a widening of the a–vO2 difference.
However, studies utilizing hypoxic inspirates to examine VO2p during the on-transient of exercise have not yielded consistent findings. Hughson & Kowalchuck (1995) reported an overall slowing of VO2p kinetics at the onset of moderate-intensity exercise while breathing a hypoxic (14% O2) gas mixture, which they attributed to a decreased delivery of O2 to working muscle. Additionally, Springer et al. (1991) reported slower phase 2 VO2p kinetics during moderate-intensity hypoxic (
15% O2) exercise in children and adults, and Engelen et al. (1996) have reported slower VO2 kinetics during heavy-intensity exercise in hypoxia. In contrast, MacDonald et al. (2000) reported that the adaptation of both muscle O2 consumption and phase 2 VO2p kinetics were similar in hypoxia and normoxia during heavy-intensity knee-extension exercise and attributed the similarity between inspirates to small (but statistically non-significant) adaptations in both muscle blood flow and O2 extraction which compensated for the decreased O2 content in hypoxia. Due to the conflicting results from previous studies (Springer et al. 1991; Hughson & Kowalchuck, 1995; Engelen et al. 1996; MacDonald et al. 2000) regarding the adaptation of O2 consumption during the exercise transient in hypoxia, further investigation of the effect of hypoxia on pulmonary O2 consumption at the onset of moderate-intensity exercise is warranted.
In the present study, near-infrared spectroscopy (NIRS) was utilized to monitor continuously the relative changes in deoxy- (HHb), oxy- (O2Hb), and total (Hbtot) haemoglobin/myoglogin during dynamic exercise. NIRS data have been shown to reflect closely the muscle metabolic rate as determined by MRS-derived PCr changes (a proxy for muscle O2 consumption), but correlated poorly with the metabolic rate determined from blood flow and a–vO2 difference measurements (Boushel et al. 1998). The NIRS-derived HHb signal reflects the balance between local muscle O2 delivery and utilization (DeLorey et al. 2003) and when used in association with measurements of pulmonary O2 consumption and limb blood flow allows for determination of the time course of local muscle O2 utilization.
Thus, the purpose of this study was to examine the adaptations of simultaneously determined VO2p, leg blood flow (LBF) and muscle deoxygenation during the on-transient of single-leg knee-extension exercise while breathing normoxic (21% O2) and hypoxic (12% O2) gas mixtures. We hypothesized that VO2p would adapt similarly in normoxia and hypoxia and that increases in both O2 delivery and O2 extraction would compensate for the decreased O2 availability in hypoxia. A secondary purpose was to examine the response of VO2p, LBF and muscle deoxygenation to an acute change in inspired O2 during steady-state exercise. Haseler et al. (1998) demonstrated that changes in inspired O2 introduced during the steady-state of moderate-intensity exercise result in altered PCr concentrations, suggesting a role for O2 in metabolic control. Thus, we reasoned that an acute hypoxic challenge presented during constant-load steady-state exercise after muscle blood flow and oxidative metabolism had adjusted to the work rate may provide further insight into the regulation of VO2p. We hypothesized that LBF and muscle deoxygenation would adjust to maintain muscle O2 availability and that VO2p would be unchanged in response to an acute increase and/or decrease in inspired O2.
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Methods |
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Seven healthy, physically active young males (age, 22 ± 1 years; height, 182 ± 8 cm; body mass, 84 ± 15 kg; mean ±S.D.) volunteered and gave written informed consent to participate in the study. All procedures were approved by the University Ethics Committee for Research on Human Subjects.
Protocol
Subjects reported to the laboratory on three separate occasions. All testing was performed on a custom-built, single-leg, knee-extension (KE) ergometer as previously described (Bell et al. 2001). Estimated lactate threshold (
L) and peak O2 uptake (VO2 peak) were determined while breathing a hypoxic (12% O2) inspirate during an incremental KE test to volitional fatigue on the first visit to the laboratory. The level of inspired O2 was regulated by a fast gas-mixing system and the dynamic end-tidal forcing technique as previously described by Poulin et al. (1993). The hallmark feature of this technique is that it regulates end-tidal gases in such a way that they are not affected by changes in pulmonary ventilation. Briefly, two microcomputers were used, one functioned as a data acquisition computer and the other functioned as a control computer. On a breath-by-breath basis the measured end-tidal gas concentrations were compared with the desired end-tidal gas concentration, which were entered into the control computer prior to the experiment. Based on the measured end-tidal gas concentration, the inspired gas flow was adjusted to reduce the mismatch between measured and desired gas concentrations on the next breath. In the hypoxic condition in the present study, inspired PO2 was adjusted on a breath-by-breath basis to maintain end-tidal O2 (PETO2) at 60 mmHg. Following a 10 min accommodation to the hypoxic inspirate, testing began at an initial work rate of 15 W and was incremented by 3 W every 2 min until the subject was unable to continue or they were unable to maintain contraction frequency at 30 min–1. Estimated lactate threshold (L) was determined by visual inspection and defined as the VO2 at which VCO2 began to increase out of proportion to VO2. From this test it was determined that a work rate of 21 W would represent moderate-intensity exercise (i.e. below L) for each subject during both normoxic and hypoxic exercise.
On the next two visits, subjects performed step-transitions of single-leg KE exercise from unloaded exercise to the moderate-intensity work rate of 21 W in either normoxia (PETO2 100 mmHg; 21% O2) or hypoxia (PETO2 60 mmHg; 12% O2) with the order of testing randomized. During one visit, testing was conducted in normoxia and began with 4 min rest, followed by 2 min unloaded KE exercise, a step-increase in work rate to 21 W performed for 10 min, and 6 min resting recovery. Following an additional 30 min resting recovery, the protocol was repeated, but in this instance, the inspirate was switched instantaneously from normoxia to hypoxia after 6 min constant-load exercise and was continued for an additional 4 min. This protocol was repeated during the final visit, except that both exercise tests were initiated while breathing the hypoxia gas mixture following a 10 min accommodation period prior to the exercise and a transition from hypoxia to normoxia was made after 6 min of the second moderate-intensity exercise bout. The protocol is summarized in Fig. 1.
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Gas exchange measurements were similar to those previously described (Babcock et al. 1994). Briefly, inspired and expired flow rates were measured using a low dead space (90 ml) bi-directional turbine (VMM 110, Alpha Technologies, Laguna Beach, California, USA), which was calibrated prior to each test using a syringe of known volume (3.01 l). Expired gases were sampled continuously at the mouth and analysed for concentrations of O2, CO2 and N2 by mass spectrometry (Morgan Medical, Rainham, Kent, UK) after calibration with precision-analysed gas mixtures. Changes in gas concentration were aligned with gas volumes by measuring the time delay for a square wave bolus of gas passing the turbine to the resulting changes in fractional gas concentrations as measured by the mass spectrometer. Data collected every 20 ms were transferred to a computer, which aligned concentrations with volume data to build a profile of each breath. Breath-by-breath alveolar gas exchange was calculated using algorithms of Beaver et al. (1981). Heart rate (HR) was monitored continuously by electrocardiogram and arterial saturation was monitored by pulse oximetry (Nonin, Plymouth, Minnesota, USA).
Femoral artery mean blood velocity (MBV) was measured using pulsed-Doppler ultrasonography (CFM 750, VingMed, Horten, Norway). Data were acquired continuously with a 7.5 MHz probe with a 45° angle of insonation placed on the skin surface 2–3 cm distal to the inguinal ligament. The ultrasound gate was maintained at full width to ensure complete insonation of the entire vessel cross-section with constant intensity (Gill, 1985). Beat-by-beat MBV was calculated by integrating the total area under the MBV profile. MBV data were recorded at 200 Hz and stored on a computer for subsequent analysis. Femoral artery diameter was measured continuously by echo-Doppler ultrasound (7.5 MHz probe) and stored to videotape for subsequent analysis. Arterial diameter was determined in triplicate at nine different time points during rest, and the steady-state of unloaded and active KE exercise for each subject. The three measures at each time point were averaged to obtain a femoral artery diameter for each subject at each time point. Leg blood flow (LBF) was calculated as LBF (ml min–1) = MBV (cm s–1)·
r2· 60, where r is the radius of the femoral artery. Leg O2 delivery was calculated as the product of LBF and CaO2. CaO2 was estimated as the product of SaO2 from pulse oximetry and the O2 content of Hb, assuming an arterial [Hb] of 15.0 g · 100 ml–1 and an O2 carrying capacity of 1.34 ml g–1 Hb.
Local muscle oxygenation profiles of the quadriceps vastus lateralis muscle group were made with NIRS (Hamamatsu NIRO 300, Hamamatsu Photonics KK, Japan). Optodes were placed on the belly of the muscle midway between the lateral epicondyle and greater trochanter of the femur. The optodes were housed in an optically dense plastic holder, thus ensuring that the position of the optodes, relative to each other, was fixed and invariant. The optode assembly was secured on the skin surface with tape, and then covered with an optically dense, black vinyl sheet, thus minimizing the intrusion of extraneous light and loss of NIR transmitted light from the field of interrogation. The thigh, with attached optodes and covering, was wrapped with an elastic bandage, to minimize movement of the optodes while still permitting freedom of movement. This preparation essentially prevented any optode movement relative to the skin surface.
The theory of NIRS has been described in detail by Elwell (1995). Briefly, one fibre optic bundle carried the NIR light produced by the laser diodes to the tissue of interest while a second fibre optic bundle returned the transmitted light from the tissue to a photon detector (photomultiplier tube, PMT) in the spectrometer. Four different wavelength laser diodes (776, 826, 845 and 905 nm) provided the light source. The diodes were pulsed in rapid succession and the light detected by the PMT. The use of four laser diodes enables more chromophores to be detected and also increases the sensitivity of the instrument, thus providing an advantage of the NIRO 300 over other simpler NIR detection systems (Chance et al. 1992; Mancini et al. 1994; Belardinelli et al. 1995). The intensity of incident and transmitted light was recorded continuously and, along with the relevant specific extinction coefficients and estimated optical pathlength, used for online estimation and display of the changes from the resting baseline of oxy- (O2Hb), deoxy- (HHb), and total (Hbtot) haemoglobin. The raw attenuation signal (in OD units) was transferred to computer and stored for further analysis.
The interoptode spacing was 5 cm. While values have been reported for differential pathlength factors (DPF) in muscle for calf and forearm (Elwell, 1995; van der Zee et al. 1992; Duncan et al. 1995), there are presently no published values for the quadriceps muscle. Due to the uncertainty of the DPF for quadriceps muscle we did not utilize a DPF in the present study, thus values for O2Hb, HHb, and Hbtot are reported as a delta (
) from baseline in units of µM·cm.
The HHb signal can be regarded as being essentially blood-volume insensitive during exercise (De Blasi et al. 1993; Ferrari et al. 1997), thus it was assumed to be a reliable estimator of changes in intramuscular deoxygenation status in the field of interrogation (De Blasi et al. 1994; Ferrari et al. 1997).
Analysis
Breath-by-breath gas exchange data were filtered for aberrant breaths, time-aligned and ensemble averaged into 5 s time bins at rest, during unloaded KE exercise and at 20, 40, 60, 120, 180 and 300 s of the exercise transition for each subject. MBV data were filtered, time aligned and interpolated to 2 s intervals (corresponding to one contraction cycle). LBF was calculated for each contraction cycle, then averaged into 5 s time bins at rest, during unloaded KE exercise and at 20, 40, 60, 120, 180 and 300 s of the exercise transition for each individual.
The NIRS-derived HHb data were filtered, time-aligned and averaged. The time to the onset of an increase in HHb following the increase in work rate was determined as the first point greater than one standard deviation above the mean of the HHb baseline. HHb, O2Hb and Hbtot signals were each averaged to 5 s bins at rest, during unloaded KE exercise and at 20, 40, 60, 120, 180 and 300 s of the exercise transition for each subject.
Statistics
Paired t-tests were used to compare all variables in normoxia and hypoxia. Repeated measures ANOVA was used to compare normoxic and hypoxic responses across different time points. Relationships amongst key variables were determined by Pearson product correlation. All data are presented as mean ±S.E. A value of P < 0.05 was considered statistically significant.
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Results |
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The mean VO2p during rest, unloaded KE exercise and at discrete time points (20, 40, 60, and 120 s) of the exercise transient and steady-state (180 and 300 s) in hypoxia and normoxia are illustrated in Fig. 2. VO2p was similar in hypoxia and normoxia at rest, and during the steady-states of unloaded and of active moderate-intensity KE exercise. However, VO2p was lower (P < 0.05) during hypoxic compared to normoxic exercise across the time points of 20, 40, 60 and 120 s of the exercise transition.
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Pulse oximetry demonstrated an approximate 9% decrease in arterial O2 saturation during hypoxia (normoxia, 97.1 ± 1.0%; hypoxia, 88.4 ± 1.0%). Thus, the estimated arterial O2 content (assuming an arterial [Hb] of 15.0 g·100 ml–1) was 195 ml l–1 in normoxia and 178 ml l–1 in hypoxia, or a 9% reduction in hypoxia.
Heart rate (HR) during unloaded KE exercise was higher (P < 0.05) in hypoxia (74 ± 4 b·min–1) than in normoxia (69 ± 3 b·min–1). However, the HR change from unloaded exercise to active exercise was greater (P < 0.05) in normoxia (17 ± 3 b·min–1) than hypoxia (13 ± 3 b·min–1), resulting in a similar end-exercise HR in hypoxia (87 ± 3 b·min–1) and normoxia (87 ± 4 b·min–1).
Leg blood flow & calculated O2 delivery
Femoral artery diameter was similar in normoxic and hypoxic conditions and did not change from resting values at any time point during exercise. In hypoxia compared to normoxia, LBF tended to be higher (by 35%) although this increase was not statistically significant (P > 0.05) during unloaded KE, the on-transient and during steady-state moderate-intensity KE exercise (Fig. 3A). Calculated leg O2 delivery also tended to be higher in hypoxia than normoxia at rest and throughout exercise (Fig. 3B), however, as with LBF, calculated O2 delivery was not statistically different between conditions.
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Following the step increase in work rate NIRS-derived HHb remained at pretransition levels for a period of 10 ± 1 s and 10 ± 1 s in hypoxia and normoxia, respectively. Following this delay, HHb increased rapidly in both hypoxia and normoxia, with a tendency to be lower (P > 0.05) throughout the exercise transient in hypoxia compared to normoxia (Fig. 4A). O2Hb decreased following the onset of exercise with a tendency for O2Hb to decrease less in hypoxia compared to normoxia at 20, 40 and 60 s of the on-transient (Fig. 4B), however, O2Hb concentration was not statistically different between hypoxia and normoxia throughout the exercise on-transient. Hbtot was 30% (P > 0.05) greater throughout the on-transient and during the steady-state of exercise in hypoxia compared to normoxia (Fig. 4C).
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There was no change in VO2p during either the switch from normoxia to hypoxia or hypoxia to normoxia (Fig. 5A). Similarly, LBF did not change during either acute switch in inspired gas mixture (Fig. 5B). HHb increased (P < 0.05) when the switch was made from normoxia (221 ± 48 µM·cm) to hypoxia (297 ± 59 µM·cm) and decreased (P < 0.05) when the switch was made from hypoxia (226 ± 54 µM·cm) to normoxia (178 ± 57 µM·cm) (Fig. 5C). O2Hb decreased (P < 0.05) when the switch was made from normoxia (–139 ± 58 µM·cm) to hypoxia (–178 ± 66 µM·cm) and increased (P < 0.05) when the switch was made from hypoxia (–113 ± 64 µM·cm) to normoxia (– 68 ± 66:µM·cm) (Fig. 5D). Hbtot increased (P < 0.05) after the switch was made from normoxia (81 ± 30 µM·cm) to hypoxia (119 ± 29 µM·cm), however, Hbtot, did not change as a result of the switch from hypoxia (113 ± 33 µM·cm) to normoxia (109 ± 35 µM·cm) (Fig. 5E).
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Discussion |
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During the transition to moderate-intensity knee-extension exercise (20–120 s) VO2p was lower (P < 0.05) in hypoxia (mean of 20, 40, 60, 120 s, 0.688 l min–1) than normoxia (0.738 l min–1). Similarly, Hughson & Kowalchuk, (1995) reported that VO2p kinetics (determined as the mean response time, MRT) were slowed during cycling exercise in hypoxia compared to normoxia and hyperoxia. Others (Springer et al. 1991; Engelen et al. 1996) have also reported slowed VO2p kinetics and a greater O2 deficit in hypoxia (Linnarsson et al. 1974). Hughson & Kowalchuk, 1995) attributed the slower VO2p kinetics to a decreased delivery of O2 to working muscles. In contrast, MacDonald et al. (2000) reported similar phase 2 VO2p kinetics and muscle O2 consumption kinetics in hypoxia and normoxia during the transition from rest to one-leg knee-extension exercise and argued that small (non-significant) increases in both MBV and O2 extraction compensated for the reduced CaO2 during hypoxia.
In the present study LBF, while not statistically different in hypoxia and normoxia, was 35% higher in hypoxia throughout unloaded KE exercise, the on-transient and steady-state of moderate-intensity KE exercise. With the magnitude of this apparent difference in LBF, the estimated O2 delivery was similar or somewhat higher in hypoxia than normoxia throughout the exercise on-transient and steady-state of exercise. Thus, the increase in LBF in hypoxia was able to compensate completely for the decreased CaO2 (Fig. 3). Despite the similar O2 delivery to the limb in hypoxia compared to normoxia, VO2p was lower throughout the exercise on-transient in hypoxia, whereas at rest, and during unloaded KE and steady-state moderate-intensity KE exercise VO2p was maintained at normoxic levels. Thus, factors other than bulk O2 delivery to the limb appear to be responsible for the lower VO2p throughout the exercise on-transient in hypoxia. These findings also raise the question: Why was an increase in O2 delivery capable of maintaining VO2p during the steady-state of exercise, but not the exercise transient?
In the present study, LBF adapted similarly during the exercise on-transient in normoxia and hypoxia. For example, at 40 s of the exercise transient, LBF was 78% and 75% of the steady-state response in hypoxia and normoxia, respectively. Thus, it appears that the main compensatory response to hypoxia was to increase the absolute level of LBF at rest and throughout exercise in hypoxia compared to normoxia, rather than altering the rate of increase of LBF. This resulted in a similar calculated O2 delivery at any time point throughout the exercise on-transient (Fig. 3). Similar to the increase in LBF, NIRS-derived Hbtot was 30% higher in hypoxia compared to normoxia throughout the exercise transient suggesting a greater local muscle Hb volume. While a direct relationship between muscle blood flow and local muscle Hb volume has not been established, a higher Hb concentration is consistent with a greater perfusion and thus O2 availability within the region of NIRS interrogation. These results suggest that compensatory adjustments in blood flow, while not statistically significant, are important functionally and are able to compensate for the reduced CaO2 in hypoxia relative to normoxia.
Following the onset of constant-load single-leg KE exercise there was a delay of approximately 10 s before an increase was seen in the HHb-NIRS signal in both normoxia and hypoxia. This delay is consistent with previous observations from our laboratory during moderate-intensity leg-cycling exercise in normoxia and has been discussed in detail (DeLorey et al. 2003). We believe that the HHb delay reflects a complex balance between Hb/Mb deoxygenation, O2 delivery and the effect of muscle contraction on microvascular volume, such that while muscle O2 uptake is most probably increasing during this period, an increase in HHb is ‘masked’ by other factors which impact on the volume of Hb in the field of NIRS interrogation. Thus, the delay may represent a period when O2 delivery meets the O2 demand without need for a widened a–vO2 difference.
Following the time delay, muscle deoxygenation (HHb) increased rapidly towards the steady-state in both normoxia and hypoxia consistent with previous observations from our laboratory at the onset of normoxic moderate-intensity leg-cycling exercise (DeLorey et al. 2003). HHb adapted at a similar rate in normoxia and hypoxia, however, there was a tendency for HHb to be lower throughout the exercise on-transient in hypoxia with HHb at 20 s of the exercise on-transient being only 52% of the steady-state response in hypoxia compared to 67% of the steady-state in normoxia suggesting a lower O2 extraction in hypoxia. A higher muscle O2 delivery and a lower O2 extraction in hypoxia compared to normoxia is consistent with previous studies of the steady-state responses in single- (Rowell et al. 1986) and double-leg (Koskolou et al. 1997) knee-extension exercise. Thus, in the present study, the lower VO2p throughout the exercise on-transient in hypoxia compared with normoxia, despite a similar O2 delivery in the two conditions adequate to support an increase in VO2p similar to that seen in normoxia, implies an inability to maintain O2 extraction in hypoxia at a level comparable to that observed in normoxia. The inability to maintain O2 extraction when LBF is elevated during submaximal exercise in hypoxia has been attributed to a reduction in red blood cell (RBC) capillary mean transit time (MTT) limiting the time available for the diffusion of O2 from capillary to mitochondria (Rowell et al. 1986; Koskolou et al. 1997). Whether the apparently reduced diffusive O2 transport in the present study was the result of a decrease in the driving pressure for O2 transport or a reduction in capillary MTT remains to be determined. Given the relatively low exercise intensity utilized, a significant effect on capillary MTT would not be expected as blood flow and presumably blood velocity would be relatively low in comparison to their peak values. However, the pressure gradient for the diffusion of O2 was reduced in the present study. PETO2 was maintained at 60 mmHg by the end-tidal forcing technique and the arterial saturation of 89% confirms that arterial PO2 was 60 mmHg in hypoxia in the present study. A decreased driving pressure for O2 transport resulting in slowed VO2p kinetics is consistent with the work of Koike et al. (1990). These authors (Koike et al. 1990) reported slowed VO2p kinetics during moderate- and heavy-intensity exercise, following carboxyhemoglobin-induced reductions in blood O2 content, which they attributed to a diffusion limitation. In contrast, Grassi et al. (1998) demonstrated that VO2p kinetics in electrically stimulated isolated canine muscle contracting at 60–70% VO2 peak were unaffected by the enhancement of peripheral O2 diffusion. Thus, the accumulated evidence from the present study and the work of Koike et al. (1990) and Grassi et al. (1998) suggests that a reduced pressure gradient for the diffusive transport of O2 is capable of slowing VO2p kinetics, however, it is unlikely that the fundamental limitation to VO2p kinetics is related to the diffusive transport of O2.
In addition to the effects of hypoxia on diffusive O2 transport, evidence exists that hypoxia may influence the control of mitochondrial respiration (Wilson & Rumsey, 1988; Hogan et al. 1992; Richardson et al. 1995) which may have important implications for the rate of muscle O2 consumption at the onset of exercise, although the effect of changes in intracellular PO2 on the control of mitochondrial respiration has recently been questioned by Marcinek et al. (2003). Whether the control of mitochondrial respiration was altered in the present study cannot be discerned, however, previous studies which utilized a similar degree of hypoxia demonstrated altered intracellular PO2 values, suggesting that a greater change in redox and phosporylation potentials may be necessary to achieve the required O2 consumption. Therefore, in the present study it appears that either a reduction in the driving pressure for O2 transport, and/or changes in the cellular energetics in hypoxia may contribute to a delayed increase in muscle O2 utilization following the onset of exercise, and consequently a delay in muscle O2 extraction (estimated from changes in muscle deoxygenation, HHb).
VO2p was not altered by an acute switch from normoxia to hypoxia, or from hypoxia to normoxia. HR and femoral artery MBV were also unchanged by either gas switch. However, local muscle HHb rapidly increased (P < 0.05) during the switch from normoxia to hypoxia and was followed by a slowly evolving increase (P < 0.05) in Hbtot. HHb decreased (P < 0.05) with the switch from hypoxia to normoxia, whereas Hbtot was unchanged (Fig. 5). A role for CaO2 in the regulation of muscle blood flow has been reported (Roach et al. 1999; Calbet, 2000). However, in the present study, leg blood flow did not change following either an increase or decrease in inspired PO2 and presumably CaO2 introduced during the exercise steady-state, instead VO2p was maintained by alterations in muscle deoxygenation. Potentially, the compensatory response to a hypoxic challenge may be different during the exercise on-transient initiated after a period of accommodation to a hypoxia inspirate than during an acute challenge during the steady-state of exercise, and the blood flow compensation may be a slow response.
In conclusion, the results of this study demonstrate that VO2p was lower during the exercise on-transient in hypoxia despite calculated leg O2 delivery being similar in hypoxia and normoxia. Thus, factors other than convective muscle O2 delivery may be responsible for the lower on-transient VO2p in hypoxia. The tendency towards a lower HHb in hypoxia compared to normoxia suggests that the ability to increase O2 extraction may have been limited in hypoxia. A decreased O2 extraction in hypoxia may be the result of a reduced pressure gradient for the diffusive transport of O2, and/or potentially intracellular PO2 induced changes in the control of mitochondrial respiration.
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