| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Canadian Centre for Activity and Aging, 2School of Kinesiology, and 3Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada N6A 3K7
Submitted 15 October 2002 ; accepted in final form 27 March 2003
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
O2p) and deoxygenation of the vastus lateralis muscle was examined during moderate-intensity leg-cycling exercise. Young adults (5 men, 6 women; 23 ± 3 yr; mean ± SD) performed repeated transitions on 3 separate days from 20 W to a constant work rate corresponding to 80% of lactate threshold. Breath-by-breath O2p was measured by mass spectrometer and volume turbine. Deoxyhemoglobin (HHb), oxyhemoglobin, and total hemoglobin and myoglobin were sampled each second by near-infrared spectroscopy (Hamamatsu NIRO-300). O2p data were filtered, interpolated to 1 s, and averaged to 5-s bins; HHb data were averaged to 5-s bins. Phase 2 O2p data were fit with a monoexponential model. For HHb, a time delay (TDHHb) from exercise onset to an increase in HHb was determined, and thereafter data were fit with a monoexponential model. The time constant for O2p (30 ± 8 s) was slower (P < 0.01) than that for HHb (10 ± 3 s). The TDHHb before an increase in HHb was 13 ± 2 s. The possible mechanisms of the TDHHb are discussed with reference to metabolic activation and matching of local muscle O2 delivery and O2 utilization. After this initial TDHHb, the kinetics of local muscle deoxygenation were faster than those of phase 2 O2p (and presumably muscle O2 consumption), reflecting increased O2
extraction and a mismatch between local muscle O2 consumption and perfusion. near-infrared spectroscopy; muscle oxygen utilization
O2p) adjusts in an exponential manner in response to a step transition in work rate. The kinetics of the phase 2 O2p response correspond to those of phosphocreatine (PCr) breakdown (27, 32) and thus presumably reflect the kinetics of muscle O2 consumption. Whether the adaptation of O2 is limited by the convective delivery of O2 to working muscles or by the activation and rate of biochemical reactions and provision of substrate for oxidative metabolism within the muscle has not been established. Simultaneous measurements of the adaptation of blood flow to an exercising limb and O2p have demonstrated that limb blood flow adjusts at a faster rate than O2p after a step-transition to a higher work rate (4, 9, 20), suggesting that muscle blood flow in the exercise on-transient is not limiting.
Near-infrared (NIR) spectroscopy (NIRS) provides continuous, noninvasive monitoring of the relative concentration changes in oxy-(O2Hb), deoxy-(HHb), and total Hb (Hbtot) and myoglobin (Mb) during dynamic exercise. Thus, in the present study, NIRS was used to examine muscle microvascular oxygenation at the onset of exercise, simultaneously with the adaptation of O2p. The NIRS-derived HHb signal provides an estimate of changes in muscle microvascular deoxygenation and thus reflects the relationship between local muscle O2 delivery and muscle O2 utilization at the site of O2 exchange within the region of NIRS interrogation.
The primary purpose of this study was to examine the temporal relationship between the adaptation of muscle O2 consumption, as reflected by the phase 2 O2p response, and deoxygenation of the vastus lateralis muscle during moderate-intensity, constant-load leg cycling exercise. It was hypothesized that the overall time course of deoxygenation would closely match that of phase 2 O2p during a moderate-intensity work rate transition, because, based on the accumulated evidence from the literature, we reasoned that muscle blood flow would not be limiting after the onset of exercise. After the onset of exercise, a delay has been reported before an increase in muscle O2 consumption in humans (4, 20) and isolated muscle preparations from animals (21), suggesting that the activation of mitochondrial respiration does not increase immediately, but is delayed relative to the start of exercise. A second purpose was to examine the deoxygenation at the exercise onset, with the hypothesis that the first increase in NIRS-derived muscle deoxygenation would be delayed at the onset of exercise, reflecting the delay before the fall in microvascular PO2, which is seen in isolated muscle preparations (7, 21).
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
Protocol. Subjects reported to the laboratory on four separate occasions. A maximal cycle ergometer ramp test (25 W/min) was performed on the first day of testing for the determination of the estimated lactate threshold (
L) and peak O2
(O2 peak). The L was defined as the O2 at which CO2 production began to increase out of proportion in relation to O2, with a systematic rise in minute ventilation-to-O2 ratio and end-tidal PO2, whereas minute ventilation-to-CO2 production ratio and end-tidal PCO2 were stable. After this test, subjects returned to the laboratory on three separate occasions to perform step transitions in work rate from 20 W to a moderate work rate selected to elicit a O2 corresponding to 80% L. Each work rate transition was 8 min in duration and was preceded and followed by 8 min of cycling at 20 W.
Measurements. Gas exchange measurements were similar to those described previously (3). Briefly, inspired and expired flow rates were measured by using a low dead space (90 ml) bidirectional turbine (Alpha Technologies VMM 110), which was calibrated before each test by using a syringe of known volume. Inspired and expired gases were sampled continuously at the mouth and analyzed for concentrations of O2, CO2, and N2 by mass spectrometry (Morgan Medical) after calibration with precision-analyzed 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 by using algorithms of Beaver et al. (5). Heart rate was continuously monitored by electrocardiogram.
Local muscle oxygenation profiles of the quadriceps vastus lateralis muscle 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 near 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 for cycling. This preparation essentially prevented any optode movement relative to the skin surface.
The theory of NIRS is described in detail by Elwell (18). Briefly, one fiber-optic bundle carried the NIR light produced by the laser diodes to the tissue of interest, whereas a second fiber-optic bundle returned the transmitted light from the tissue to a photon detector (photomultiplier tube) 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 was detected by the photomultiplier tube. 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 (8, 13, 26). The intensity of incident and transmitted light was recorded continuously at 2 Hz and, along with the relevant specific extinction coefficients and optical path length, used for online estimation and display of the concentration changes from the resting baseline of O2Hb, HHb, and Hbtot. The raw attenuation signals (in optical density units) were transferred to computer and stored for further analysis.
The interoptode spacing was 5 cm. Whereas values exist for differential path length factors (DPF) in muscle for calf and forearm (17, 18, 39), 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 change from baseline in units of micromoles per centimeter.
The HHb signal can be regarded as being essentially blood-volume insensitive during exercise (14, 19); thus it was assumed to be a reliable estimator of changes in intramuscular oxygenation status and O2 extraction in the field of interrogation (15, 19).
Analysis. Breath-by-breath gas exchange data were filtered for aberrant data points, interpolated to 1-s intervals, ensemble averaged, and then averaged into 5-s time bins to yield a single response for each subject. Phase 2 O2p kinetics were determined from the phase 1-phase 2 interface to the end of minute 3
of work by the use of a monoexponential model of the form
 | (1) |
O2p at any time t, b is the baseline value of Y at the point in time from which the data were fitted, A is the amplitude of the increase in Y
above the baseline value, 
is the time constant defined as the duration of time through which Y increases to a value equivalent to 63% of A, and TD is the time delay.
The NIRS-derived O2Hb, HHb, and Hbtot data were time aligned and ensemble averaged to 5-s time bins to yield a single response for each subject. The time to the onset of an increase in HHb was determined as the first point greater than one standard deviation above the mean of the baseline. This analysis was performed on the second-by-second data for each of the individual trials; the time delay was then calculated as the average of the three trials for each subject. HHb data were then fit from the time of initial increase in HHb to 90 s with a monoexponential model of the form in Eq. 1 to determine the time course of muscle deoxygenation. Although we are not certain that the underlying processes determining muscle deoxygenation are exponential in nature, visual inspection of the NIRS-derived HHb signal and analysis of least squares residuals suggested that fitting with a monoexponential model would provide a reasonable estimate of the time course of muscle deoxygenation (i.e., estimated ) (Fig. 1). The O2Hb and Hbtot signals did not approximate an exponential response, and these data were not modeled; however, the response of these signals was compared qualitatively to the HHb data at corresponding time intervals.
|
Statistical analysis. Student's t-test was used to determine gender differences in height, mass, and peak exercise values. Two-way analysis of variance was used to test for the effect of gender on O2p and HHb kinetics. Comparison of O2p and HHb kinetics was by paired t-test. Relationships among key variables were determined by Pearson product correlation. All data are presented as means ± SD. A P value of <0.05 was considered statistically significant.
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
O2 peak
(P < 0.01). Relative O2 peak (ml · kg-1 · min-1) was not different between men and women. Two-way ANOVA revealed that the of the O2p and estimated HHb responses were not different between men and women; thus the group data were collapsed into a single data set for the comparison of O2p and HHb kinetics.
|
The adaptations of O2p, HHb, O2Hb, and Hbtot during the on-transient of a step increase in work rate for a single subject are presented in Fig. 2. The early phase (i.e., first 120 s) of the adaptation for HHb, O2Hb, and Hbtot
is presented in Fig. 3 for the same subject. Phase 2O2p
increased in an exponential manner at the onset of exercise, with the of the response being 30 ± 8 s. NIRS-derived HHb remained at pretransition levels for a period of 13 ± 2 s after the step increase in work rate (Table 2). After the time delay, HHb increased rapidly to a steady state in every subject, the time course of which was characterized by an estimated of 10 ± 3 s (Table 2). The adaptation of HHb during the on-transient was faster than the adaptation of phase 2 O2p (P < 0.01) (Table 2). Additionally, the time course for the change in HHb determined as the time delay plus estimated (23 ± 4 s; Table 2) was faster (P < 0.05) than the of the phase 2 O2p kinetics (30 ± 8 s). Thus the time necessary to attain a steady-state response for HHb (<1 min; i.e., 13-s delay plus 4 time constants) compared with O2p (2 min for 4 time constants) was markedly different. The O2p was not correlated with the estimated HHb response, nor was it correlated with the sum of the HHb time delay and estimated .
|
|
|
O2Hb decreased transiently (3 ± 2 s) immediately after the onset of exercise, and this was followed by an additional, gradual decrease in O2Hb, which reached a nadir at 47 ± 14 s, after which O2Hb increased steadily throughout the remainder of the exercise bout. Similarly, Hbtot decreased transiently (3 ± 2 s) at the onset of exercise and reached a nadir in 17 ± 14 s. Thereafter Hbtot showed a variable response and either 1) remained below baseline levels (for 
156 ± 58 s) before progressively returning to baseline and then increasing to levels higher than baseline throughout the remainder of the exercise (n = 6); 2) returned to and remained at baseline levels (for 56 ± 3 s) before increasing further for the remainder of the exercise (n = 3); or 3) returned rapidly to baseline and then increased above baseline for the remainder of the exercise (n = 2).
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
O2p kinetics) and NIRS-derived muscle deoxygenation during constant-load, moderate-intensity, leg-cycling exercise. The NIRS-derived HHb signal provides a continuous, noninvasive measurement of changes in muscle deoxygenation and reflects the balance between local muscle O2 delivery and O2
utilization. The main findings of this study were that 1) at the onset of exercise, a delay exists before an increase in muscle deoxygenation, as measured by the NIRS-derived deoxygenation (HHb) signal; 2) after this delay, the rate of adaptation of muscle deoxygenation was rapid, being faster than the adaptation of the phase 2 O2p and, presumably, muscle O2 consumption, and reflecting an increased O2
extraction and increased volume of deoxygenated Hb-Mb in the active muscle microvasculature as a consequence of an increase in the muscle O2
consumption-to-muscle perfusion ratio within the region of NIRS interrogation; 3) NIRS-derived Hbtot decreased below the pretransition baseline at the onset of exercise, reflecting a decrease in Hbtot-Mb content within the muscle, possibly due to a muscle pump-mediated decrease in microvascular volume early in exercise; and 4) Hbtot then returned to, and increased above, baseline levels, with considerable variation in the time course, possibly due to individual variability in local muscle blood flow regulation. NIRS. To date, examination of the adaptation of local muscle blood flow and O2 extraction in the microvasculature of the exercising human has not been possible.
Studies examining the factors responsible for the regulation of muscle O2 consumption during the on-transient of exercise have relied on measurements of bulk blood flow in large conduit arteries to exercising limbs, combined with sampling of arterial and venous blood at discrete time points for calculation of arteriovenous O2 difference [(a-v)O2]. However, this methodology precludes analysis of local tissue oxygenation changes consequent to perfusion-metabolism mismatching. There are also limitations of the methodology. The influence of blood-perfusing inactive muscle groups may contribute to an elevated mixed-venous O2 content and lead to an underestimation of local muscle O2. Additionally, the inability to sample continuously limits the data points available for the accurate determination of the time course of O2 across an exercising limb. Furthermore, the determination of arterial (or tissue)-to-venous sampling site transit delays, which may change from rest and throughout exercise, dependent on changes in perfusion pressure, vasodilation, and/or vascular compression, makes identification of the onset of O2
extraction somewhat tenuous.
NIRS provides noninvasive and continuous monitoring of the relative concentration changes of O2Hb, HHb, Hbtot, and Mb in localized regions of muscle throughout the transition to, and into the steady state of, dynamic exercise in humans. NIRS measurements primarily reflect changes in the small arterioles, capillaries, and venules (10), with the capillary volume accounting for 84% of the muscle microvascular volume (29). Thus any change in HHb presumably is a consequence of a change in O2 extraction and microvascular deoxygenation at the site of O2 exchange and reflects the balance between O2 delivery and O2 utilization in the localized region of muscle being interrogated by NIRS. NIRS data have been shown to reflect closely the muscle metabolic rate, as determined by magnetic resonance spectroscopy-derived PCr changes (a proxy for muscle O2
consumption), but correlated poorly with the metabolic rate determined from blood flow and (a-v)O2 measurements (12). As noted by Van Beekvelt et al. (38), the Fick method of determining metabolic rate provides a more global assessment of whole muscle O2 consumption, and, because of possible metabolism-perfusion mismatching in an exercising limb (22), a close relationship with NIRS estimates of O2 utilization in an active region of muscle is unlikely.
Comparison of phase 2 O2p and HHb adaptation. Visual inspection of the postdelay increase in the NIRS-HHb signal suggested that the data could be adequately fit by a monoexponential model to describe the time course of HHb adaptation. After the time delay, HHb increased rapidly toward a "steady-state" level (estimated = 10 ± 3 s), suggesting that muscle perfusion or the local distribution of blood flow and O2 delivery in the on-transient of moderate-intensity cycling exercise was not adequate to meet the metabolic demand of the muscle, thus requiring a rapid increase in O2
extraction. The delayed recovery of NIRS-derived Hbtot and O2Hb back to baseline levels after an initial decrease at the onset of exercise also might suggest an underperfusion relative to the metabolic demand in the area of muscle insonated by NIRS in several subjects (See Hbtot and muscle blood flow below for discussion of Hbtot response).
Comparison of the for phase 2 O2p with both the estimated for HHb (Table 2) and the combined estimated plus time delay for HHb (Table 2) revealed that muscle deoxygenation increased at a faster rate than phase 2 O2p. Although it is recognized that the O2p
represents the whole muscle, whereas the HHb reflects a small area, these data suggest that, at the microvascular level, the degree of mismatch between local muscle perfusion and metabolism requires that O2 extraction increase rapidly, as seen in the rapid increase in the NIRS-HHb signal, to support the metabolic demand of the tissue. Bangsbo et al. (4) reported a rapid increase in O2 extraction after an initial delay, with (a-v)O2
reaching 50 and 90% of the maximum exercise response in 13 and 51 s, respectively, corresponding to a 63% response time of 19 s, similar to the present study, in which the estimated plus time delay for HHb was 23 ± 8 s. In the present study, the rapid increase in HHb after a delay suggests that, at the muscle microvasculature level, perfusion is not adequate to meet the metabolic demand of the tissue.
Hbtot and muscle blood flow. Increases in muscle blood flow during exercise are the result of increases in cardiac output mainly directed toward exercising muscle and increases in vascular conductance. Previous measurements of bulk muscle blood flow and O2 have demonstrated a coupling of blood flow and O2 at the muscle level (33), with a 6 l/min increase in blood flow required for a 1 l/min increase in O2 during leg-cycling exercise (40). Furthermore, findings from this (9) and other laboratories (25, 35) have provided evidence of faster kinetics for leg (femoral artery) blood flow relative to O2p, suggesting that O2 delivery was adequate or in excess of muscle O2
consumption during the exercise transition. However, the control of exercise hyperemia is believed to be a local phenomenon (24), and the distribution of blood flow between (1, 2, 22) and within (30) muscles is not uniform; thus areas of under- and overperfusion relative to metabolic demand seem likely.
The NIRS-derived Hbtot signal represents the time course and magnitude of change in Hbtot concentration relative to a baseline value in the local area of muscle interrogated by NIRS. The Hbtot signal reflects the balance between local muscle blood flow, the effect of muscular contraction on vascular Hb volume, vasodilation, hemoconcentration, and capillary recruitment. Factors such as hemoconcentration, capillary recruitment, local vasodilation, and/or an increase in local muscle blood flow may contribute to an increase in Hbtot during exercise, whereas increased muscle pressure and vascular compression associated with muscular contraction may decrease Hbtot in the local area of muscle interrogated by NIRS. As a consequence, a relationship between changes in Hbtot and changes in blood flow should be viewed with caution. Most obvious, Hbtot represents the volume in the area of insonation, whereas increases in blood flow may be accomplished by an increase of blood velocity with no change in the volume of the area.
In the present study, an early decrease of Hbtot followed by a relatively long time delay (120 s in 6 of 11 subjects) before an increase in Hbtot above baseline was observed. The early decrease in Hbtot suggests an effect of muscular contraction and vascular compression on vascular volume early in exercise. In agreement, Kindig et al. (23) reported an immediate increase in blood flow, accompanied by a decrease in capillary hematocrit at the onset of contractions in the isolated rat spinotrapezius muscle. The delayed recovery of Hbtot back to baseline levels observed in several subjects (i.e., 120 s in 50% of the subjects) in this study suggests that the regulation of muscle Hb volume, and perhaps local control of vascular conductance, is highly variable across individuals and that the increase in regional Hb content may be much different than the adaptation of bulk flow to the limb.
Delay before HHb increase. After the onset of constant-load, moderate-intensity cycling exercise, a time delay of 13 s was observed before an increase in the NIRS-derived HHb signal above preexercise baseline levels. In agreement with this finding, in humans, significant reductions in venous O2 content [and widening of the (a-v)O2] were not observed until 15–20 s after the onset of moderate-intensity leg cycling exercise (20), and 6 s (after correction for tissue-to-sampling site transit delay) in heavy-intensity, knee-extension exercise (4). Grassi et al. (20) and Bangsbo et al. (4) argued that the early increase in muscle O2 was accomplished primarily by an early increase in muscle blood flow with O2 extraction delayed at the onset of exercise. In animal models where phosphorescence-quenching techniques were used to monitor PO2, Hogan (21) reported an 12-s delay before a fall in cytosolic PO2 in stimulated single Xenopus muscle fibers (Mb deficient), and Behnke et al. (7) reported an 15- to 20-s delay before a decrease in microvascular PO2 in stimulated rat spinotrapezius muscle. In both of these studies (7, 21), the cytosolic and microvascular PO2 appeared to decrease in an exponential manner after the initial time delay, a pattern mimicked by the HHb data in the present study.
The rate of change of the NIRS-derived HHb signal reflects the balance between muscle O2 delivery and muscle O2 utilization. Therefore, a delay before an increase in muscle deoxygenation could reflect 1) an appropriate matching of blood flow and muscle O2 consumption, such that the required O2 demand is satisfied by increased O2 delivery without greater O2 extraction; 2) a metabolic inertia, in which activation of mitochondrial respiration and muscle O2 consumption is delayed relative to the onset of exercise; 3) an early deoxygenation of intracellular Mb (tending to increase the HHb signal) combined with a reduction in intravascular HHb because of a relative increase in blood flow to metabolic rate (tending to decrease the HHb signal), with the resultant HHb signal remaining unchanged at baseline levels at the onset of exercise; and/or 4) a redistribution of Hb (both HHb and O2Hb) out of the field of NIRS interrogation (with the muscle contraction), which would decrease the HHb signal and offset an early increase in O2 extraction after the onset of exercise.
If the increases in muscle O2 consumption were supported only by an increase in muscle blood flow and muscle O2 delivery (i.e., no additional increase in O2 extraction), blood flow would be required to increase in excess of the five- to sixfold increase normally seen for a given increase in muscle O2 consumption (33). Limb blood flow measurements made at the conduit artery suggest that the muscle pump rapidly increases limb blood flow at exercise onset (36). Whether the muscle pump has the flow-generating capability necessary to increase muscle blood flow to this extent cannot be discerned from this study. However, in the present study, the role of the muscle pump in contributing to an immediate increase in muscle blood flow was presumably minimized as moderate-intensity exercise was preceded by a baseline of 20-W cycling, not rest. Behnke et al. (6), using separate measures of microvascular PO2
(7) and capillary hemodynamics (23) in the isolated rat spinotrapezius muscle, concluded that muscle O2 consumption increased within the first 2s of exercise and that muscle blood flow and O2 delivery were not limiting at the onset of exercise. If muscle O2 consumption increases immediately at the onset of exercise, as Behnke et al. (6) suggest, then the constant HHb NIRS signal during the first 13 s of exercise in this study may reflect a close matching of perfusion and metabolism.
If muscle blood flow were to increase in excess of the muscle metabolic requirement, the concentration of HHb would be expected to decrease due to a lower O2 extraction and a lower Hb desaturation consequent to the delivery of more oxygenated blood to the region of muscle interrogated by NIRS. However, in the present study, the NIRS-HHb signal remained at or above baseline levels throughout the exercise on-transient, suggesting that, within the region of NIRS interrogation, local perfusion was not in excess of metabolic demand.
If a "metabolic inertia" existed, where an increase in O2 extraction and Hb desaturation were delayed after the onset of exercise, a constant HHb would be anticipated until a significant activation of muscle O2 consumption had occurred. In the present study, the 13-s time delay before an increase in muscle deoxygenation could reflect a delay before the activation of muscle oxidative metabolism. Our data agree with those of Hogan (21), who reported an 13-s delay before a decrease in intracellular PO2 in isolated, intact, single Xenopus fibers at the onset of exercise. However, as noted, the recent analysis of Behnke et al. (6) argues against a delay in muscle oxygen consumption. Furthermore, a delay before the onset of O2 utilization is not supported by several magnetic resonance spectroscopy studies (32, 42, 27), which have reported an almost immediate monoexponential decrease in PCr, a proxy for muscle O2 consumption (42), at exercise onset. Also, a delay in activation of muscle O2 consumption coupled with a muscle pump-mediated increase in muscle perfusion should be reflected by a decrease in O2 extraction and Hb desaturation (i.e., decrease in NIRS-HHb), and this was not the case in the present study, suggesting that a metabolic delay is unlikely.
The delay before an increase in HHb could also be explained by an early increase in intracellular Mb deoxygenation, which is offset by an equal and opposite decrease in intravascular Hb deoxygenation consequent to a muscle pump-mediated increase in local perfusion. At present, NIRS instrumentation is unable to accurately determine the relative contribution of Mb to the total NIRS signal, because the Mb absorption spectrum overlaps that of Hb (16). Tran et al. (37) used 1H-magnetic resonance spectroscopy to study changes in muscle deoxy-Mb and HHb in combination with NIRS and observed that, during plantar flexion exercise with pressure cuffing of the leg, NIRS deoxygenation kinetics closely matched those of Mb desaturation, but not Hb desaturation. In contrast, Mb desaturation was reported to follow that of Hb deoxygenation by Wang et al. (41) and Mancini et al. (26). Furthermore, Mb levels are small relative to those of Hb, and several studies (11, 13, 26, 34) have suggested that intracellular Mb contributes <10% to the total NIRS signal. Thus the preponderance of evidence in the literature would suggest that NIRS primarily monitors changes in vascular Hb oxygenation and deoxygenation. Whereas Mb desaturation occurs at relatively low intensities of exercise and Mb-associated stores may provide an important source of O2 at the onset of exercise (31), there is only an 50% deoxygenation seen at peak exercise (31, 28). In the present study, the relative contribution of Mb to the total NIRS signal cannot be determined. Until this can be quantified and the temporal adaptation of Mb desaturation is determined, this issue cannot be resolved, and the potential contributions of Mb to the increase in muscle O2 consumption at exercise onset cannot be overlooked.
Additionally, a redistribution of Hbtot (i.e., O2Hb and HHb) out of the field of NIRS interrogation could occur with the sudden increase in muscle pressure at exercise onset, such that an early increase in HHb, because of an activation of muscle O2 consumption and increased O2 extraction, would be viewed as a return of the NIRS-HHb signal back toward, rather than above, baseline levels. In the present study, the immediate decrease in O2Hb and Hbtot after the onset of exercise is consistent with a redistribution of Hb out of the region of NIRS interrogation; however, the HHb signal did not decrease. The majority of Hb in the vascular space (i.e., arterial and venular) at the onset of an exercise transition initiated from 20 W might be expected to be oxygenated and represent a large percentage of the Hbtot, whereas the HHb concentration would be a small percentage of the Hbtot, reflecting the low level of O2 extraction necessary to support the metabolic rate. Thus a small decrease in HHb as a consequence of a muscle pump-mediated decrease in vascular volume might be offset by an early increase in muscle O2 consumption and HHb desaturation, such that the net effect would be an unchanged HHb concentration.
Therefore, the unchanged NIRS-HHb signal seen in the 13 s after the initiation of exercise in the present study likely reflects a complex balance between Hb-Mb deoxygenation, O2 delivery, and the effect of muscle contraction on microvascular volume, rather than a "metabolic inertia," such that the increase in HHb that would be expected after an increase in muscle O2 consumption and increased O2
extraction is "masked" by factors that impact on the volume of Hb in the field of NIRS interrogation.
In conclusion, in examining the relationship between the adaptation of O2p and HHb during a work rate transition from 20 W to moderate-intensity exercise, the results of this study demonstrated that NIRS-derived muscle deoxygenation did not change from pretransition levels for 13 s after the onset of exercise and then increased rapidly toward the steady state, with the time course of the adaptation being markedly faster than the adaptation of O2p. The delay after the onset of exercise before a change in HHb was similar to the reports of the microvascular PO2 profile and, while suggestive of a metabolic inertia, more likely reflects an early increase in muscle O2 consumption, which is not observed as an increase in HHb due to the effects of muscular contraction on vascular Hb volume. After the delay, contrary to the hypothesis, there was a faster time course of the HHb response relative to the adjustment of O2p, suggesting that the early increase in O2p is accomplished by a rapid increase in O2 extraction and an early widening of the (a-v)O2.
|
ACKNOWLEDGMENTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
|
FOOTNOTES |
|---|
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.
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  A. J. Harper, L. F. Ferreira, B. J. Lutjemeier, D. K. Townsend, and T. J. Barstow Matching of blood flow to metabolic rate during recovery from moderate exercise in humans Exp Physiol, October 1, 2008; 93(10): 1118 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Borghi-Silva, C. Carrascosa, C. C. Oliveira, A. C. Barroco, D. C. Berton, D. Vilaca, E. B. Lira-Filho, D. Ribeiro, L. E. Nery, and J. A. Neder Effects of respiratory muscle unloading on leg muscle oxygenation and blood volume during high-intensity exercise in chronic heart failure Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2465 - H2472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F. Ferreira, S. Koga, and T. J. Barstow Dynamics of noninvasively estimated microvascular O2 extraction during ramp exercise J Appl Physiol, December 1, 2007; 103(6): 1999 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Koga, D. C. Poole, L. F. Ferreira, B. J. Whipp, N. Kondo, T. Saitoh, E. Ohmae, and T. J. Barstow Spatial heterogeneity of quadriceps muscle deoxygenation kinetics during cycle exercise J Appl Physiol, December 1, 2007; 103(6): 2049 - 2056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Lai, G. M. Saidel, B. Grassi, L. B. Gladden, and M. E. Cabrera Model of oxygen transport and metabolism predicts effect of hyperoxia on canine muscle oxygen uptake dynamics J Appl Physiol, October 1, 2007; 103(4): 1366 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. DeLorey, J. M. Kowalchuk, A. P. Heenan, G. R. duManoir, and D. H. Paterson Prior exercise speeds pulmonary O2 uptake kinetics by increases in both local muscle O2 availability and O2 utilization J Appl Physiol, September 1, 2007; 103(3): 771 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. K. Chin, R. J. Leigh, G. J. F. Heigenhauser, H. B. Rossiter, D. H. Paterson, and J. M. Kowalchuk Hyperventilation-induced hypocapnic alkalosis slows the adaptation of pulmonary O2 uptake during the transition to moderate-intensity exercise J. Physiol., August 15, 2007; 583(1): 351 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Clanton Hypoxia-induced reactive oxygen species formation in skeletal muscle J Appl Physiol, June 1, 2007; 102(6): 2379 - 2388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Forbes, J. M. Kowalchuk, R. T. Thompson, and G. D. Marsh Effects of hyperventilation on phosphocreatine kinetics and muscle deoxygenation during moderate-intensity plantar flexion exercise J Appl Physiol, April 1, 2007; 102(4): 1565 - 1573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. F. Ferreira, D. M. Hueber, and T. J. Barstow Effects of assuming constant optical scattering on measurements of muscle oxygenation by near-infrared spectroscopy during exercise J Appl Physiol, January 1, 2007; 102(1): 358 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Harper, L. F. Ferreira, B. J. Lutjemeier, D. K. Townsend, and T. J. Barstow Human femoral artery and estimated muscle capillary blood flow kinetics following the onset of exercise Exp Physiol, July 1, 2006; 91(4): 661 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. MacPhee, J. K. Shoemaker, D. H. Paterson, and J. M. Kowalchuk Kinetics of O2 uptake, leg blood flow, and muscle deoxygenation are slowed in the upper compared with lower region of the moderate-intensity exercise domain J Appl Physiol, November 1, 2005; 99(5): 1822 - 1834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. F Ferreira, A. J Harper, D. K Townsend, B. J Lutjemeier, and T. J Barstow Kinetics of estimated human muscle capillary blood flow during recovery from exercise Exp Physiol, September 1, 2005; 90(5): 715 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zuo and T. L. Clanton Reactive oxygen species formation in the transition to hypoxia in skeletal muscle Am J Physiol Cell Physiol, July 1, 2005; 289(1): C207 - C216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. DeLorey, J. M. Kowalchuk, and D. H. Paterson Adaptation of pulmonary O2 uptake kinetics and muscle deoxygenation at the onset of heavy-intensity exercise in young and older adults J Appl Physiol, May 1, 2005; 98(5): 1697 - 1704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
