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1 Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1; 2 Laboratoire des sciences du sport, 25030 Besançon cedex, France; and 3 School of Physical and Health Education and Department of Physiology, Queen's University, Kingston, Ontario, Canada K7L 3N6
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We
tested the hypothesis that increases in forearm blood flow (FBF) during
the adaptive phase at the onset of moderate exercise would allow a more
rapid increase in muscle O2 uptake
(
O2 mus). Fifteen subjects
completed forearm exercise in control (Con) and leg occlusion (Occ)
conditions. In Occ, exercise of ischemic calf muscles was
performed before the onset of forearm exercise to activate the muscle
chemoreflex evoking a 25-mmHg increase in mean arterial pressure that
was sustained during forearm exercise. Eight subjects who increased FBF
during Occ compared with Con in the adaptation phase by >30 ml/min
were considered "responders." For the responders, a higher
O2 mus accompanied the
higher FBF only during the adaptive phase of the Occ tests, whereas
there was no difference in the baseline or steady-state FBF or
O2 mus between Occ and Con.
Supplying more blood flow at the onset of exercise allowed a more rapid
increase in O2 mus supporting our hypothesis that, at least for this type of exercise, O2 supply might be limiting.
blood pressure; Doppler velocimetry; handgrip exercise; metabolic control; ischemia
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THE LONG-STANDING
DEBATE over whether the rate of increase in muscle O2
consumption at the onset of exercise is limited by adjustments in
O2 delivery or metabolic inertia has received substantial attention in recent years (3, 4, 6, 8, 9, 12, 21, 25, 27).
Recently, Grassi et al. (8) have shown that increasing the
blood flow before the onset of electrically stimulated, isolated dog
muscle contractions did not significantly alter the rate of increase in
muscle O2 uptake
(O2 mus). They took this to
mean that, at least in isolated dog muscle, the adaptation of aerobic
metabolism was limited by a metabolic inertia that was independent of
O2 supply in both the high-flow and normal-flow conditions.
These same investigators also examined O2 mus at the onset of
submaximal leg cycling exercise by humans (9). They
concluded from this human experimentation that bulk O2
delivery to the exercising muscle was in excess during the first
15 s of exercise (9). After this very early phase,
these researchers were unable to resolve whether a bulk O2
delivery or biochemical inertia set by the accumulation of metabolic
substrate determined the rate of increase in
O2 mus.
More recently, Bangsbo et al. (3) measured and accounted
for blood flow transit time across working leg muscles in determining O2 mus in a high-intensity
[~120% peak O2 uptake
(O2)], single-leg exercise model. After
transit times were accounted for, their measurements indicated that the
onset of increasing O2 mus
occurred sooner than described by Grassi et al. (9). These
investigators also concluded that, because the difference between
O2 delivery and consumption remained constant after the
first 15 s of exercise and because O2 extraction was
not maximal, the initial increase in
O2 mus was not limited by
O2 delivery. However, intracellular
PO2 can reach levels of 4 Torr or less even
though O2 extraction is in the range of 60-70%
(18, 26). Therefore, the hypothesis that adjustment in
O2 mus is limited by
O2 delivery cannot be determined from the pattern of
response of a single exercise condition.
In our laboratory (13), we observed that when metabolic
demand and blood flow were manipulated during exercise at two different work rates in two different arm positions (above and below heart level), a faster adjustment in blood flow resulted in a faster adjustment in O2 mus. It
might be argued that the above-heart position actually provided a
circulatory disadvantage that caused reductions in availability of
O2 at the onset of exercise, if the arm below heart
position is assumed to be "normal." Therefore, to test the
link between O2 supply and oxidative metabolism during
adaptation to exercise, it is important to create conditions in which
flow is elevated above normal to determine whether O2
delivery has an impact on
O2 mus adaptation.
Recently, our laboratory reported on an exercise model in which forearm
blood flow (FBF) adapted more rapidly during the early phase of
exercise (22). To accomplish this more rapid increase in
early FBF, subjects performed ischemic calf muscle exercise followed by sustained ischemia before the onset of forearm
exercise (22). An elevated mean arterial blood pressure
(MAP) accompanying the ischemic muscle chemoreflex response was
responsible for the elevated FBF during the early stages of forearm
exercise (22). In the present study, we set out to
investigate the effect of this elevated FBF on muscle oxidative
metabolism. The subjects' exercising arms were positioned at heart
level, which was assumed to be the normal position. We hypothesized
that the more rapid increase in FBF during forearm exercise with
chemoreflex-mediated increase in MAP would cause
O2 mus to rise more rapidly
to the steady state. Subjects performed forearm exercise under control
conditions (Con) and during sustained occlusion of blood flow to
previously exercised calf muscle (Occ).
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects. The experiments were carried out on 15 healthy volunteers (12 men, 3 women, age 24 ± 1 yr). As described later, these subjects were divided into responder and nonresponder groups on the basis of whether they had increased FBF during the first minutes of forearm exercise in the Occ condition. The two women and six men (age 25.2 ± 1.3 yr) and one woman plus six men (23.5 ± 0.8 yr) formed the responder and nonresponder groups, respectively. Within each group there were sedentary individuals and recreational and varsity-level athletes; however, none of the subjects specifically trained the forearm muscles. After reading a description of the methods and possible risks, each person signed a consent form approved by the Office of Research Ethics at the University of Waterloo. Each subject practiced the exercise protocols to become familiar with the potential discomfort and the experimental design and data collection procedures so that high-quality Doppler signals could be obtained in both conditions. Subjects were asked to abstain from caffeine and alcohol ingestion and strenuous exercise for 24 h before any data-collection day. Their maximal voluntary isometric contraction (MVC) strength was 45.0 ± 2.2 kg during handgrip exercise as determined from the best of three attempts. When considered in the individual groupings, the MVC values were 49.0 ± 3.8 and 32.0 ± 3.4 kg for the male and female responder subjects, respectively, and 46.5 ± 1.4 nonresponder male subjects (P = 0.3 for comparison between male responder and nonresponder subjects).
Experimental design. The subjects assumed a supine position and had a 21-gauge Teflon catheter inserted retrograde to flow into a deep vein in the antecubital fossa to obtain samples of blood draining the exercising muscles of the forearm. Subjects continued to lie supine with their right arms supported in an extended position at approximately heart level before starting the testing. Room temperature was held constant at ~23°C but could not be cooled below this level because of limitations in the cooling system. To reduce skin blood flow, there was always a fan directed on the forearm. Whenever we noted diastolic flow during the rest period, a fine spray of water was applied to the skin surface to assist in cooling. Thus we were able to minimize skin blood flow contributions to rest and exercise total FBF.
Dynamic handgrip exercise was achieved by lifting and lowering a load at a contraction-relaxation duty cycle of 1 s-2 s performed in time with a sound signal. The load was equivalent to 20% of the subject's MVC (9.0 ± 0.4 kg). The load was lifted in ~0.5 s and lowered over ~0.5 s, followed by the forearm resting for 2 s before the next contraction; thus there was no isometric contraction period and force was constant throughout each handgrip. The experimental tests included an observation period during which signals were monitored to ensure a stable baseline. After this, data were collected during 1 min of rest followed by 5 min of contractions. Each subject completed two different exercise protocols, applied in balanced order, on the same day. At least 20 min separated the trials, and again signals were monitored to confirm return to a stable baseline. The Occ tests were conducted to alter the exercise-induced blood flow response. The calf muscles were made ischemic by inflation of cuffs immediately below the knee to a suprasystolic pressure (250 mmHg) as described previously (22). Plantar flexion calf muscle exercise was performed before testing to stimulate the ischemic muscle chemoreflex response. Typically, 2-4 min of ischemic exercise was required to increase MAP ~25 mmHg above resting levels. This elevated MAP was maintained with continued ischemia. At the end of forearm exercise, the circulatory arrest cuffs were rapidly deflated. The responses of Occ were compared with those of Con, in which baseline and exercise conditions were monitored without occlusion cuffs on the legs.Blood flow data collection and analysis. Heart rate (HR), MAP, and mean blood velocity (MBV) were measured beat by beat. MAP was measured by using a photoplethysmograph finger blood pressure cuff (Ohmeda 2300, Finapres, Englewood, CO) on the middle finger of the left hand. MBV was measured with a flat 4-MHz pulsed Doppler ultrasound probe (Multigon Industries, model 500V, Mt. Vernon, NY) fixed to the skin over the brachial artery immediately proximal to the catheter. The angle of the transducer crystal relative to the skin was 45°, and the ultrasound gate was maintained at full width to facilitate insonation of the total width of the artery with minimal wall movement noise. The exact angle of the probe to the vessel was determined by echo Doppler imaging (Toshiba model SSH-140 A, Tochigi-Ken, Japan) to measure the skin-to-vessel angle. Audio and visual feedback of the intensity of the Doppler spectrum allowed us to obtain a clear Doppler signal at rest and during exercise. Beat-by-beat MBV was calculated by taking the average velocity across each cardiac cycle. All data were saved continuously at 100 Hz via analog-to-digital conversion (Metrabyte DAS-16, Taunton, MA) on a computer data-acquisition system.
Brachial artery diameter was measured by echo Doppler at rest and immediately after exercise with a hand-held linear 7.5 MHz probe operating in B-Mode. The imaged data were stored on videotape for subsequent analysis. Each diameter measurement was the average from three different sets of on-screen calipers taken from a frozen-screen image at the same point of the cardiac cycle during diastole. Forearm blood flow (FBF) was obtained beat-by-beat as the product of MBV and arterial cross-sectional area as FBF = MBV ·
r2, where r is the
vessel radius. To obtain a continuous estimate of FBF (Fig.
1) while smoothing the effects of
contraction (23, 24), we binned data into 3-s windows to
include a full contraction and relaxation cycle. An index of forearm
vascular conductance (FVC) was calculated as FBF/MAP.
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Blood sampling.
A three-way stopcock was fixed to the catheter. For both conditions,
1-ml venous blood samples were collected into heparinized syringes at
60 and 30 s of rest, then at 30, 60, 120, and 300 s of the
exercise transition. The blood samples were immediately agitated gently
and stored in an ice bath until analysis within 45 min of collection.
All whole blood samples were analyzed for hematocrit, venous blood
gases, pH, and lactate by using selective electrodes in a blood
gas-electrolyte analyzer (Nova StatProfile 9 Plus, Nova Biomedical,
Mississauga, ON). Hemoglobin concentration and O2
saturation were obtained with a CO oximeter (Nova CO-oximeter, Nova
Biomedical, Mississauga, ON). The analyzers were calibrated regularly
during the analysis period.
O2 mus.
O2 mus was calculated from
the Fick principle as the product of FBF and arteriovenous
O2 content difference (a-vDO2).
Values were calculated at discrete times for each subject corresponding
to the timing of blood samples. At each of the sample points during
exercise, a total of four contraction-relaxation cycles, centered on
the time points indicated, were included to estimate FBF. Because there
is a transit time from capillaries to the venous sampling point
(3), we obtained the blood samples in the latter half of
this sample period to achieve the best match between FBF and
O2 extraction. The same procedure was used in both the Con
and Occ trials. The estimate of O2 extraction was obtained
by first assuming a constant arterial O2 content (97%
saturation is commonly measured by oximetry in our laboratory) and
assuming that hemoglobin was the same as in venous blood and then
subtracting the measured venous O2 content to yield
a-vDO2. Given the minimal demand placed on the
cardiovascular system by moderate forearm exercise, it is reasonable to
assume that arterial O2 saturation would remain constant at
a value observed commonly in our laboratory by ear oximetry. This
assumption has been confirmed in our laboratory with direct
measurements of arterial blood during more strenuous leg kicking
exercise (14). Sustained postexercise muscle
ischemia normally does not affect end-tidal PCO2 (19) so there would be
minimal effects on alveolar PO2 and especially
on arterial O2 content. For these reasons, we did not
believe it was ethically justified to insert an arterial catheter.
Data analysis. All resting data are the mean values of all sample points during the rest period. For analysis during exercise, discrete sample points were obtained to correspond to the times at which blood samples were taken. Mean values were taken as the average of four contraction/relaxation duty cycles (12 s).
Statistics.
During visual inspection of the data, we found that the subjects
grouped into two distinct patterns, those for whom Occ caused an
elevation in FBF in the first 2 min of exercise (responders, n = 8) and those for whom it did not (nonresponders,
n = 7). We adopted an objective criterion to define the
responders based on the difference in FBF (
FBF) between the Occ and
Con trials. Responders were identified as those individuals who had at
least two values of FBF during the adaptive phase of the experiment (i.e., 30, 60, or 120 s) in which the Occ trial exceeded the Con trial by at least 30 ml/min (see solid symbols for responders in Fig.
1). To test the validity of this separation, we conducted two-way
repeated measures ANOVA on the main effects of time and responder vs.
nonresponder to determine whether a difference existed for each of
FBF and change in O2 uptake
(O2). The analysis indicated
significant main effects of time and of responder vs. nonresponder for
each of FBF and O2. We continued
our data analysis by comparing the main effects of condition (Con and
Occ) and time within responder and nonresponder groups with two-way repeated-measures ANOVA. After finding a significant main effect (i.e.,
P < 0.05), we further analyzed individual time points
by Student-Newman-Keuls post hoc test for P < 0.05. All data are presented as means ± SE.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Sustained ischemia before and during the Occ tests caused
significant elevations in HR and MAP (shown in Fig.
2 for the responders only,
n = 8). In the baseline, HR was greater in Occ than in
Con (74.1 ± 4.4 vs. 63.3 ± 3.3 beats/min, respectively;
P < 0.05) and MAP was ~27% greater in Occ than in
Con (117.1 ± 3.4 vs. 91.9 ± 3.8 mmHg, respectively;
P < 0.05). These effects of Occ were maintained
throughout the exercise period with no further change as a consequence
of exercise (Fig. 2). The nonresponders had resting baseline HR of
63.0 ± 3.5 in Occ vs. 53.7 ± 1.7 in Con and baseline MAP of
119.1 ± 4.6 in Occ vs. 97.1 ± 6.1 in Con (both
P < 0.05). Although there was a difference in absolute
HR, there were no differences in the pattern of HR or MAP between the
responder and nonresponder groups during exercise (data not shown).
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The evolution of the FBF and FVC responses at rest and during exercise
is shown for the responder group in Fig. 2. The increase in FBF was a
function of increased velocity of blood flow; there was no significant
change in brachial artery diameter from pre- to postexercise in either
Con (4.13 ± 0.08 to 4.18 ± 0.08 mm) or Occ (4.08 ± 0.10 to 4.14 ± 0.08 mm) tests. Resting FBF was not different
between Occ and Con even though MAP was elevated, because FVC was
reduced by 23% (P < 0.05). With the initiation of
exercise, FBF increased rapidly to ~120 ml/min in the first 15-20 s in each of the Occ and Con conditions and then
progressively increased with a different pattern in Occ vs. Con to
steady-state values near 200 ml/min. As noted, visual inspection
indicated that not all subjects responded in the same manner. Those
individuals who were responders had a significant increase in FBF at
all three time points in the adaptive phase (0.5, 1, and 2 min) during
the Occ compared with the Con condition (Fig.
3, top). The elevated FBF in
the Occ condition occurred as a consequence of similar early increases
in FVC in both the Occ and Con tests (Fig. 2) whereas MAP was elevated
in the Occ compared with Con tests. That the nonresponder group did not
have a significant increase in FBF can be appreciated from the FBF
in Fig. 1. In the nonresponders, MAP was elevated to the same extent as
in the responders, but FVC remained lower throughout the Occ test,
preventing an increase in FBF. At 5 min, when FBF was not different
between Occ and Con for either the responders or nonresponders, FVC was
significantly reduced by 15% in Occ compared with Con.
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Measured venous O2 content did not differ at rest between the Con (131 ± 14 ml O2/l) and Occ (141 ± 11 ml O2/l) conditions nor did it differ at any point during exercise (Fig. 3, bottom). Given the assumption of constant arterial O2 content, this meant that there were no differences between conditions for the calculated a-vDO2.
The rapid increase in both FBF and a-vDO2 meant
that O2 mus increased from
~2 ml/min at rest to 15 ml/min or more by 30 s of exercise (Fig.
3). The consequence of elevated FBF and no change in
a-vDO2 in the responder group during the Occ
trial was a significant increase in
O2 mus at each of 30 s
and 1 and 2 min of exercise compared with the Con condition (Fig. 3).
The relationship between FBF and
O2 mus is further
emphasized in Fig. 1, where data for all 15 subjects are presented to
differentiate between responder and nonresponder at the three time
points observed during the rest-to-exercise transition. The overall
regression coefficient (r = 0.77) indicated a
significant linear relationship (P < 0.0001).
Venous blood lactate concentration was not different at rest between the Con (1.4 ± 0.1 mmol/l) and Occ (1.2 ± 0.1 mmol/l) conditions nor did it differ at any point during the exercise period. The venous blood lactate concentration at the end of 5 min of forearm exercise was 1.8 ± 0.2 and 1.9 ± 0.2 mmol/l for Con and Occ conditions, respectively, with no difference between responder and nonresponder groups.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The main finding of this study was that elevated FBF in the first
2 min of exercise in the Occ condition was associated with a
significantly greater
O2 mus during this early
phase of exercise in the human forearm.
O2 mus was not different
between Con and Occ by the end of the exercise test. These results are
consistent with our hypothesis and suggest that provision of greater
O2 supply early in exercise allowed oxidative metabolism to
increase more rapidly to the steady state. Our results from exercising
human forearm contrast with those of Grassi et al. (8),
who found that increasing blood flow before initiating electrical
stimulation of isolated dog gastrocnemius muscle did not significantly
alter the rate of increase in
O2 mus. It is probable that
species and experimental model differences accounted for the findings
in these two studies.
Methodological considerations.
In this study, we estimated
O2 mus in the human forearm
by the combination of Doppler ultrasound to measure arterial blood flow
and venous blood sampling to determine O2 extraction.
Doppler ultrasound has been well established as a reliable technique to
determine instantaneous blood flow in human skeletal muscle (20,
24). Blood was sampled from a catheter placed in a retrograde
direction into a deep forearm vein and, combined with cooling of the
skin surface, this served to minimize any contribution of blood flow
from skin vessels to the venous blood sample. It is recognized that
this is a limitation in the human model compared with the animal model,
in which it is possible to obtain blood from an isolated muscle
(8).
O2 mus between the Con and
Occ trials. That is, under conditions in which we expected to see no
difference, there was indeed no difference, giving increased confidence
in the reproducibility of our methods. Previous research from our laboratory (20) found that the coefficient of variation
for FBF during exercise was ~10% when measured for approximately the same duration as that of the present study, in which we included four
complete contraction-relaxation cycles. The calculated coefficient of
variation for FBF was larger at each exercise time point in the present
study (20-30%) because work rate was established by forearm
exercise at a percentage of MVC rather than at a fixed work rate. As
noted, the consistent values for
O2 mus under steady-state
conditions during Con and Occ trials strongly suggest high validity
during the transient phase also. One potential source of error in
measurement of FBF relates to distribution between muscle and skin.
There is no reason to suspect that increases in skin blood flow would
have contributed selectively to the measured increase in FBF for the
Occ trials only during the transition phase when MAP was elevated
throughout the 5 min of exercise.
An important aspect of the experimental design of this study was the
selection of a normal arm position. We elected the supine posture with
the arm extended at heart level. This position means that gravity
neither increased nor decreased perfusion pressure. Given the moderate
intensity of the exercise challenge in a very small muscle mass, this
task did not stress the ability of the central components of the
cardiovascular system to respond. The very small increase in venous
blood lactate concentration at 5 min of exercise confirmed the moderate
nature of the exercise challenge. Thus there is no reason to suspect
that the normal response would be impaired with the arm at heart level.
Muscle chemoreflex and cardiovascular response.
Activation of the muscle chemoreflex was used as a tool to elevate
blood flow during the transition from rest to exercise, allowing us to
directly test the hypothesis that the normal blood flow response was
limiting the adjustment of
O2 mus. Occ caused ~25
mmHg increase in MAP that was sustained during the forearm exercise
protocol. In addition to the increase in MAP, heart rate was
significantly elevated by ~10 beats/min at rest and during exercise.
The absence of any forearm exercise effect on heart rate confirmed the
relatively mild cardiovascular demands of the forearm exercise task.
O2 mus would be elevated if
FBF were also elevated during the adaptive phase of exercise. Thus from a methodological perspective we were justified in separating responders from nonresponders. Typically in physiology experiments the subject pool is treated as a homogenous entity that should not be arbitrarily divided posttest. There was no physical characteristic that
distinguished the responder and nonresponder groups although the lower
HR in nonresponders might suggest a higher parasympathetic activity to
the heart. However, there is precedent for viewing distinct response
patterns to postexercise ischemia. Rowell and colleagues (19) previously identified two distinct mechanisms by
which subjects maintained elevated MAP during sustained
ischemia. Some individuals elevated MAP primarily by increases
in vasoconstriction whereas others elevated HR and cardiac output. We
observed in the present experiments that local peripheral vascular
responses to exercise during elevation of MAP by activation of the
muscle chemoreflex could differ between individuals. Factors such as the relative density of 
- and 
-adrenergic receptors, their
stimulation by neurally released or circulating norepinephrine and
epinephrine (17), and interaction with local metabolites
could influence the individual cardiovascular response. The constancy
of O2 mus when FBF was not
elevated either during the entire test for the nonresponder group or at
5 min exercise for the responder group further suggests that the
measured O2 mus was not
influenced by circulating catecholamines but was influenced by FBF and
O2 supply.
O2 mus in the
rest-to-exercise transition.
The main purpose of our study was to investigate, in humans, the
hypothesis that increasing FBF at the onset of exercise would permit a
more rapid adaptation of
O2 mus during
moderate-intensity exercise. There are many claims in the literature
based on human (3, 4, 6, 9, 25, 27) and animal (7,
8) experimentation that O2 is always supplied in
excess of the requirements during the transition from rest to exercise.
Thus these investigators concluded that
O2 mus is established
solely by inertia of the muscle biochemistry. If this hypothesis were
correct, then increasing the supply of O2 during the
transition phase would have been associated with reduced extraction so
that O2 mus was unaltered. As we observed, calculated a-vDO2 was not
reduced during the rest-to-exercise transition in the Occ compared with
Con, although FBF was significantly elevated. That is, our model with
increased supply of O2 appeared to permit the more rapid
increase in O2 mus, suggesting that metabolic inertia alone did not limit oxidative phosphorylation at the onset of exercise. This contrasts with the
electrically stimulated dog gastrocnemius muscle, in which the rate of
increase in O2 mus was not
significantly different between conditions of spontaneous flow and a
fast O2 delivery model (8). Thus, in the
isolated dog muscle preparation in which muscle activation is achieved by maximal stimuli to the motor nerve, blood flow appears to be adequate in the rest-to-exercise transition and the rate of increase in
O2 mus might be dictated by
the inertia of the metabolic pathways. This could be a consequence of
the highly oxidative nature of the fast and slow fatigue-resistant fibers in dog compared with human muscle (15).
O2 mus. The time for leg
blood flow to increase to 63% [33.7 ± 9.2 (SD) s] was very
similar to the time for
O2 mus to increase to 63%
(35.6 ± 8.4 s). This similarity between the adaptation for
blood flow and O2 mus was
consistent with observations from our laboratory in exercising human
forearm (13). In the present study, we did not determine 63% response time because our first data point was at 30 s, which was after the 63% value in some tests. However, it is clear from Fig.
2 that the response times of both FBF and
O2 mus were faster during
Occ than Con. Recently Bangsbo et al. (3) suggested that
supply of O2 did not limit the rate of increase in
O2 mus at the onset of
severe intensity (~120% peak
O2 mus) exercise. Because the required O2 mus
exceeded the peak value and conditions of increased O2
supply were never tested, the role of O2 in regulation of
oxidative metabolism remains to be determined for this type of exercise.
At the onset of exercise, the intracellular environment undergoes
dramatic changes to support the increased demand for ATP (2, 4,
21). Oxidative metabolism adapts as a function of the
mitochondrial redox potential and phosphorylation potential (2,
4, 5). Elegant work by Wilson et al. (26) at the cellular level, Hogan et al. (11) at the organ level, and
more recently Haseler et al. (10) in humans clearly
demonstrated that, to maintain the same absolute rate of oxidative ATP
production at a lower PO2, it is necessary to
alter the phosphorylation potential with relatively greater breakdown
of phosphocreatine. Richardson et al. (18),
through application of magnetic resonance spectroscopy, observed rapid
decreases in PO2 to ~3 mmHg in normoxia and 2 mmHg in hypoxia at the onset of light exercise. These values are within the range in which alterations in phosphorylation potential are required, compared with O2-saturating conditions, to
achieve steady-state oxidative energy production (1, 2, 5, 11,
26). We recently summarized a scheme describing these complex
interactions of O2 and intracellular metabolic controllers
at the onset of exercise (21). In the present experiments
in which it appears that more O2 was available at the onset
of exercise in the Occ condition, this would imply higher intracellular
PO2 requiring relatively less change in the
phosphorylation potential to attain the measured
O2 mus.
In conclusion, our results support the hypothesis that increasing the
supply of blood flow at the onset of what we consider to be normal
conditions of moderate-intensity dynamic forearm exercise permitted a
more rapid increase in
O2 mus. These findings, in
contrast with observations from dog muscle (8), are
consistent with the important role of O2 in establishing metabolic state (phosphorylation and redox potentials) required to
attain a given level of oxidative phosphorylation not only in
steady-state exercise (1) but also at the onset of
exercise. When taken together with other observations in humans of
relatively low intracellular PO2 across a range
of submaximal work rates (18), the data reinforce the
critical role of the cardiovascular system in setting the conditions
for muscle metabolism.
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ACKNOWLEDGEMENTS |
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We are grateful to David Northey for excellent technical assistance and to Brent Winnett, Drew Harvey, Andrew Betik, and Mike Edwards for help with data collection.
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FOOTNOTES |
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This research was supported by the Natural Sciences and Engineering Research Council of Canada. Stéphane Perrey was supported by a grant from the Franche-Comté Regional Council in France.
Address for reprint requests and other correspondence: R. L. Hughson, Dept. of Kinesiology, Univ. of Waterloo, Waterloo, ON, Canada N2L 3G1 (E-mail: hughson{at}uwaterloo.ca).
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.
Received 18 January 2001; accepted in final form 6 July 2001.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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30 ml/min. Regression line for all data
points (r = 0.77, P < 0.0001)
indicates consistent relationship between early exercise 
and solid line) and during sustained
activation of the chemoreflex in the calf muscles (Occ,
and dotted line). Lines represent group averages,
whereas symbols give means ± SE at specific time points for 8 subjects who were classified as responders during the entire 60 s
of rest and for 12-s windows centered on the data points during
exercise. *P < 0.05 between Occ and Con.
