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CO2 and
E kinetics during moderate- and
heavyintensity exercise after acetazolamide administration
1 The Centre for Activity and
Ageing, The effect of carbonic anhydrase inhibition with
acetazolamide (Acz) on CO2 output
(
control of breathing; carbonic anhydrase; end-tidal partial
pressure of carbon dioxide; carbon dioxide output kinetics; ventilation
kinetics
CARBONIC ANHYDRASE (CA), the enzyme that catalyzes the
reversible hydration-dehydration reaction involving
CO2-HCO There is evidence from both animal (12, 13, 26, 27) and human (23, 28)
studies demonstrating an attenuated or abolished peripheral
chemoreceptor response after acetrazolamide (Acz) administration. In
humans, the kinetics of the Thus the purpose of this study was to examine the effect of acute
Acz-induced CA inhibition on the kinetics of
Subjects.
Seven healthy male subjects [age 24 ± 1 (SE) yr, height 178 ± 1 cm, and weight 80 ± 3 kg] participated in this study.
The experimental protocol and all possible risks associated with
participation in the study were outlined, and informed consent was
obtained from each subject. The study was approved by The University of Western Ontario Review Board for Health Sciences Research involving Human Subjects.
General protocol, materials, and methods.
Each subject performed preliminary testing consisting of an incremental
exercise test to volitional fatigue in which the work rate increased as
a ramp function by 25 W/min. Exercise was performed on an
electromagnetically braked cycle ergometer (model H-300-R, Lode). The
ventilatory threshold (
ABSTRACT
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
CO2) and ventilation
(E) kinetics was examined
during moderate- and heavy-intensity exercise. Seven men
[24 ± 1 (SE) yr] performed cycling exercise during
control (Con) and Acz (10 mg/kg body wt iv) sessions. Each subject
performed step transitions (6 min) in work rate from 0 to 100 W
[below ventilatory threshold
(<ET)] and to an
O2 uptake corresponding to ~50%
of the difference between the work rate at
ET and peak
O2 uptake [above ventilatory
threshold (>ET)].
E and gas exchange were measured breath
by breath. The time constant (
) was determined for exercise
<ET by using a single-exponential
model (fit between 20 s and end-exercise); the mean response time (MRT)
was determined for exercise >ET by
using a three-component model (fit from the start of exercise).
CO2 kinetics were slower in
Acz (<ET, = 45 ± 6 s;
>ET, MRT = 75 ± 10 s) than Con
(<ET, = 34 ± 6 s;
>ET, MRT = 54 ± 7 s).
During <ET exercise,
E kinetics were slower in Acz ( = 48 ± 6 s) than Con ( = 34 ± 6 s), but >ET kinetics were faster in
Acz (MRT = 85 ± 17 s) than Con (MRT = 106 ± 16 s).
Carbonic anhydrase inhibition slowed
CO2 kinetics during both moderate- and heavy-intensity exercise, demonstrating impaired CO2 elimination in the
nonsteady state of exercise. The slowed
E kinetics in Acz during exercise
<ET is consistent with a mechanism
coupling E kinetics with the flow of
CO2 to the lungs.
INTRODUCTION
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
3, plays an important role in facilitating the transport of
CO2 from the active tissues to the
lungs, where it is eliminated. In general, evidence suggests that,
during whole body exercise in humans, CA inhibition does not impair
CO2 output
(CO2) at rest or during the
steady state of moderate-intensity exercise (24) but may reduce
CO2 during maximal exercise
(14, 15, 22). Whereas most studies focus on the transport and
elimination of CO2 during steady-state conditions, no information is available on the effects of CA inhibition on the kinetics of
CO2 in the nonsteady state of
whole body exercise in humans. We hypothesized that slowed CO2 kinetics may contribute,
in part, to the lower peak
CO2 observed during CA
inhibition in maximal exercise (14, 15, 22). A slowing of
CO2 kinetics may occur with
CA inhibition, as there appears to be
CO2 retention in the tissues with
increasing exercise intensities (24). This increase in
CO2 storage may cause
CO2 kinetics to be slowed in
a manner similar to the slowed response observed when the capacitance
for CO2 storage is increased by
prior hyperventilation (31). Additionally, if the exercise intensity is
moderate, the kinetics of ventilation (E)
may also be slowed under conditions of CA inhibition, given the
demonstrated coupling between
CO2 and
E (31). At higher exercise intensities associated with a sustained increase in plasma lactate concentration ([La]pl),
CO2 and
E kinetics become more complex as the
contribution of CO2 from
nonmetabolic sources to CO2
increases (i.e., buffering of lactic acid by bicarbonate and a
reduction in CO2 stores by hyperventilation), and E is stimulated by
the developing metabolic acidosis. Typically,
CO2 kinetics are
unchanged, whereas E kinetics are slowed
as exercise intensities increase (8). This increase in
CO2 production may provide an
additional CO2 load that may,
under conditions of CA inhibition, result in a further slowing of
CO2 kinetics.
E response appear to be influenced by the peripheral chemoreceptor drive, particularly during the nonsteady state of exercise (for review see
Ref. 29). The effect of Acz administration on the peripheral chemoreceptor and the ensuing E response
during the onset of either moderate- or heavy-intensity exercise is not
known. A slowed ventilatory response may be observed, independent of
CO2 kinetics, if the
peripheral chemoreceptor is functionally inhibited by Acz.
CO2 and
E during the on-transition to
moderate-intensity [i.e., below the ventilatory threshold
(<ET)] and heavy-intensity
[i.e., above the ventilatory threshold
(>ET)] constant-load exercise. A
slowing of CO2 kinetics
during the on-transient of exercise would be consistent with CA being
functionally significant in the facilitation of
CO2 transport and elimination
during whole body exercise, particularly in the nonsteady state of
exercise. In addition, a slowing of E
kinetics during CA inhibition would be an expected consequence of
slowed CO2 kinetics, if a
tight coupling between
CO2 and E is causally related. Alternatively,
slowed E kinetics may be
expected independent of CO2
kinetics, if CA inhibition affects peripheral chemoreceptor function.
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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ET) and peak
O2 uptake
(O2 peak), defined as
the highest O2 uptake
(O2) averaged
over a 20-s interval, were determined from the incremental exercise
test. The ET was defined as the
O2 at which there was a
systematic increase in the ventilatory equivalent for
O2
(E/O2)
and end-tidal PO2 (PETO2) with no concomitant
increase in the ventilatory equivalent for
CO2
(E/CO2)
or decrease in end-tidal PCO2 (PETCO2).
E were
made throughout the exercise protocol; blood samples were obtained
during loadless cycling (0 W) 1 min before the onset of exercise and at
0, 15, 30, and 45 s and at 1, 1.5, 2, 3, 4, and 6 min during the
exercise bout (i.e., time 0 = onset of
exercise transition).
CO2 and
E kinetics, each subject performed two
step transitions to an absolute work rate
<ET (100 W) and one
transition to a work rate >ET. The
exercise intensity >ET corresponded
to a work rate estimated to elicit a
O2 equivalent to
ET plus ~50% of the difference
between the O2 at
ET and
O2 peak. The exercise
protocol was performed during six visits to the laboratory (3 visits
for each condition) for a total of six repetitions for the moderate-
and three repetitions for the heavy-intensity exercise; the two
moderate-intensity exercise bouts always preceded the heavy-intensity
exercise bout. Each step transition in work rate was 6 min in duration
with 6 min of loadless cycling (0 W) between each bout. The Con and Acz
exercise sessions were performed in a randomized order. We noted,
during pilot studies, that minor side effects associated with this high dose of Acz were noticeable by the subjects, and, therefore, no placebo
was used in the present study.
Inspired and expired airflow and volumes were measured during exercise
by a low-resistance, low-dead-space (90 ml) bidirectional turbine and
volume transducer (VMM-110, Alpha Technologies), which was calibrated
before each test with a syringe of known volume (990 ml). Respired
gases were sampled continuously at the mouth (1 ml/s) by a mass
spectrometer (MGA-1100, Perkin Elmer) for determination of the
fractional concentrations of O2,
CO2, and
N2. The mass spectrometer was
calibrated with precision-analyzed gas mixtures before each test.
Analog signals from the mass spectrometer and turbine transducer were
sampled every 20 ms and stored on disk for later analysis.
Breath-by-breath computations for
O2,
CO2, E,
PETO2, and
PETCO2 were performed after accounting for delays in the gas-exchange analysis system and fluctuations in lung-gas stores in the computer algorithms (1). Corrections for temperature and water vapor were made for conditions measured near the mouth. Heart rate was monitored by using an electrocardiogram with the electrodes placed in a modified V-5 configuration.
Arterialized venous blood was drawn into syringes containing lithium
heparin, mixed, placed in a slurry of ice and water, and analyzed after
a short delay. Whole blood samples (200 µl) were analyzed at 37°C
for plasma pH, arterial PCO2
(PaCO2), and
[La]pl
by using selective electrodes (Statprofile 9 Blood Gas and Electrolyte
Analyzer, Nova Biomedical Canada). The electrodes were calibrated
before each test and at regular intervals during analysis. Plasma
H+ concentration
([H+]) was calculated
from the measured pH; plasma HCO3 concentration ([HCO3]) was
calculated from the measured pH and
PaCO2.
Data analysis.
The breath-by-breath data obtained during each of the step increases in
work rate were linearly interpolated at 1-s intervals, time aligned,
and ensemble averaged to provide a single response for each subject in
each condition. The computer model utilized to describe the kinetic
response provides an estimate of the baseline (BL), amplitude (Amp),
time delay (TD), and time constants (). For step changes in work
rate <ET, the kinetic parameters for the on-transition in work rate were determined as a function of time
(t) by using a single-exponential
model
![<IT>Y</IT>(<IT>t</IT>) = BL + Amp ⋅ [1 − <IT>e</IT><SUP>−(<IT>t</IT>−TD)/&tgr;</SUP>] ⋅ <IT>u</IT>](/content/vol86/issue5/fulltext/1534/img001.gif)
|
(1) |
CO2 or
E at time
t, u = 0 for t <TD, and
u = 1 for
t >TD. A single-component model,
starting 20 s after the onset of exercise (i.e., phase
1 was ignored), was used to isolate the
phase 2 response. In addition, a large
overshoot in E was observed
in phase 1 for two subjects, and,
therefore, the response could not be adequately described by using a
two-component model.
For step changes in work rate >ET,
the kinetic parameters for the on-transition in work rate were
determined by using a three-component exponential model starting at the
onset of
exercise
![<IT>Y</IT>(<IT>t</IT>) = BL + Amp<SUB>1</SUB> ⋅ [1 − <IT>e</IT><SUP>−(<IT>t</IT>−TD<SUB>1</SUB>)/&tgr;<SUB>1</SUB></SUP>] ⋅ <IT>u</IT><SUB>1</SUB>](/content/vol86/issue5/fulltext/1534/img002.gif)
|
![+ Amp<SUB>2</SUB> ⋅ [1 − <IT>e</IT><SUP>−(<IT>t</IT>−TD<SUB>2</SUB>)/&tgr;<SUB>2</SUB></SUP>] ⋅ <IT>u</IT><SUB>2</SUB>](/content/vol86/issue5/fulltext/1534/img003.gif)
|
![+ Amp<SUB>3</SUB> ⋅ [1 − <IT>e</IT><SUP>−(<IT>t</IT>−TD<SUB>3</SUB>)/&tgr;<SUB>3</SUB></SUP>] ⋅ <IT>u</IT><SUB>3</SUB>](/content/vol86/issue5/fulltext/1534/img004.gif)
|
(2) |
ET and
>ET was determined by the MRT. The
MRT is equivalent to the time taken to reach ~63% of the difference
between BL and the new steady-state value.
Statistics. Kinetic parameter estimates were analyzed by using a two-way repeated-measures analysis of variance for Con vs. Acz and moderate- vs. heavy-intensity exercise as the main effects. Blood data were analyzed for condition (Con vs. Acz) and time effects by using a two-way repeated-measures analysis of variance. When condition was not a factor, data were analyzed by using a one-way repeated-measures analysis of variance. A significant F ratio was further analyzed by using Student-Newman-Keuls post hoc analysis. Statistical significance was accepted at P < 0.05. All values are reported as means ± SE.
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RESULTS |
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METHODS
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DISCUSSION
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The O2 peak achieved by
the subjects during the preliminary ramp exercise test was 53.8 ± 2.3 ml · kg1 · min1.
The work rates utilized during the constant-load tests were 100 W (74 ± 3% ET) and 237 ± 9 W
(138 ± 2% ET; 51 ± 1% of ~50% of the difference between the
O2 at
ET and
O2 peak) for the
<ET and
>ET exercise intensities, respectively.
The effect of Acz administration on
O2 kinetics during moderate- and heavy-intensity exercise is reported in detail in a separate communication (21). Briefly, Acz did not affect either the steady state
or the kinetics of the
O2 response
to the step transitions in exercise intensity performed in this study.
E and gas exchange at rest and
during loadless cycling.
The ventilatory and gas exchange response to acute Acz administration
during loadless cycling is presented in Table
1. Although no effects of Acz
administration were observed for
CO2 or
E during loadless cycling, the
E/CO2
was higher (P < 0.05) in Acz than in
Con. PETO2 was similar
between conditions, but, during loadless cycling,
PETCO2 was lower
(P < 0.05) during Acz.
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Acid-base status during moderate- and heavy-intensity exercise.
The effect of acute Acz administration on the acid-base status in
equilibrated plasma is presented in Table 1 and Fig.
1. Acz was administered acutely to examine
the effect of CA inhibition on
CO2 and
E kinetics without the confounding
influence of a metabolic acidosis that occurs when Acz is administered
chronically. The <ET and
>ET protocols were completed in a
single testing session, and thus the pre- and postinfusion values for
resting blood data were determined before the
<ET exercise bout (Table 1). At rest,
no difference in plasma
[H+] was observed
after Acz administration. A small but significant increase
(P < 0.05) in plasma
[H+] was observed in
Acz during loadless cycling before exercise <ET and
>ET (Table 1). Plasma
[H+] increased
(P < 0.05) during exercise
<ET and
>ET, with a higher
(P < 0.05) plasma
[H+] in Acz (Fig. 1,
A and
B). Plasma
[HCO3] was not affected by
Acz infusion at rest or during loadless cycling. Plasma
[HCO3] decreased
(P < 0.05) during exercise in Con,
but in Acz plasma [HCO3]
decreased (P < 0.05) only
during heavy-intensity exercise (Fig. 1,
C and
D). Plasma
PaCO2 was similar at rest and during
loadless cycling in Con and Acz (Table 1). Plasma
PaCO2 remained at rest levels throughout moderate-intensity exercise in both conditions (Fig.
1E). During heavy-intensity
exercise, PaCO2 decreased
(P < 0.05) in Con but remained at
rest levels in Acz (Fig. 1F);
PaCO2 was higher
(P < 0.05) in Acz than Con at the
end of heavy-intensity exercise.
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CO2 and
E kinetics during moderate-intensity
exercise.
A summary of the model parameters derived for
CO2 and
E during the on-transient to a step
increase in work rate of moderate intensity is presented in Table
2. The response of a single
subject and the group mean response to a step increase to
moderate-intensity exercise are presented in Figs. 2 and 3,
left, respectively.
The increase in
CO2 from loadless cycling to
end-exercise was similar between conditions, resulting in a similar
end-exercise CO2 (Con, 1.687 ± 0.055 l/min; Acz, 1.625 ± 0.048 l/min). Compared with Con,
the increase in E from loadless cycling
was greater (P < 0.05) in Acz, so
that the end-exercise E was also higher (P < 0.05) in Acz (48.6 ± 2.3 l/min) than in Con (42.5 ± 1.6 l/min).
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CO2 and
E during moderate-intensity exercise are
presented in Table 2. Both the BL and Amp for
CO2 were similar between Con
and Acz. CO2 was
slowed (P < 0.05) during Acz (45 ± 6 s) compared with Con (34 ± 6 s). BL
E was similar in Con and Acz studies; the
Amp for E was higher
(P < 0.05) in Acz (19.4 ± 1.0 l/min) than Con (14.2 ± 1.3 l/min). Compared with Con, the
E was slowed
(P < 0.05) in Acz (Acz, 48 ± 8 s; Con, 34 ± 6 s).
CO2 and
E kinetics during heavy-intensity
exercise.
The model parameters determined for
CO2 and
E during the on-response for a step
increase to heavy-intensity exercise are summarized in Table
3. The response of a single subject and the group mean response to heavy-intensity exercise are presented in Figs.
4 and 3,
right, respectively. Although the
total Amp (Con, 3,019 ± 124 ml/min; Acz, 2,979 ± 146 ml/min)
and end-exercise CO2 (Con,
3.816 ± 0.218 l/min; Acz, 3.657 ± 0.134 l/min) were similar in Con and Acz,
Amp2 was lower
(P < 0.05) and
Amp3 was higher during Acz than
Con. The overall time course for the increase in
CO2, as determined
by the MRT, was slower (P < 0.05) in
Acz (75 ± 10 s) than in Con (54 ± 7 s), although the kinetic
parameters, TD and , for the individual components of the
exponential model were similar in Con and Acz.
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E was similar between
conditions, the end-exercise E was higher
(P < 0.05) during Acz (124.2 ± 6.6 l/min) than Con (111.7 ± 8.6 l/min).
E on-kinetics, as determined by the MRT,
were faster (P < 0.05) in
Acz (85 ± 17 s) than Con (106 ± 16 s). The faster MRT was
associated with a faster (P < 0.05) 3 during Acz than Con, as there
were no other differences in the model parameter estimates.
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DISCUSSION |
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ABSTRACT
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DISCUSSION
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This is the first study to examine the effects of Acz-induced CA
inhibition on the kinetic responses of
CO2 and
E during whole body exercise in humans.
The unique findings of this study were that, compared with the
uninhibited condition, CO2
kinetics were slowed during the on-transient to both moderate- and
heavy-intensity exercise after CA inhibition with no effect on the
steady-state CO2 response.
Whereas E kinetics were also slowed
during the on-transient of moderate-intensity exercise in Acz, they
became faster during heavy-intensity exercise with CA inhibition.
Limitations due to CA inhibition.
A limitation of the present study and other studies examining the
effect of CA inhibition on CO2
transport and ventilatory control is the
CO2-HCO3
disequilibrium that exists in tissue and pulmonary capillary blood (3,
4, 7, 24). Acz administration resulted in a negative end-tidal-arterial PCO2 difference during moderate- and
heavy-intensity exercise (Fig. 5)
consequent to the PaCO2 (measured at
equilibrium) being consistently higher than
PETCO2. This finding, consistent with previous studies (14, 25), reflects the slower rate of CO2 formation from plasma
and erythrocyte HCO3 during the
relatively short pulmonary capillary transit time, resulting in a lower
alveolar PCO2 when CA was inhibited. The incomplete equilibration of
CO2 species in the pulmonary
capillaries leads to a progressive increase in
PaCO2 in the circulating blood and in
blood sampled for analysis. Thus the
PaCO2 determined in vitro reflects the
complete equilibration among all forms of
CO2 in the blood and does not
reflect the PaCO2 in vivo at the time of
sampling.
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CO2 during moderate- and
heavy-intensity exercise.
In agreement with previous studies (2, 24), steady-state
CO2 was not affected by CA
inhibition either at rest or at the end of moderate- or heavy-intensity
exercise. Swenson and Maren (24), using the same dose of Acz as used in
the present study, showed that
CO2 was not affected by CA
inhibition during heavy-intensity exercise because of compensatory
mechanisms that maintained
CO2; however, they did
demonstrate that complete inhibition of CA would result in a lower
CO2 during maximal exercise.
Kowalchuk et al. (14) observed a reduction in peak CO2 (~32%) during
short-term maximal exercise after a protocol of Acz administration
similar to that used in the present study. Whereas end-exercise
CO2 during moderate- and
heavy-intensity exercise was similar in Con and Acz in the present
study, the kinetics of CO2
were slowed at the onset of both moderate- and heavy-intensity exercise
in Acz, suggesting that, before achieving a steady-state,
CO2 is depressed to a greater
extent in the CA-inhibited condition.
]pl
(i.e., >ET),
CO2 kinetics become more
complex because of additional contributions from aerobic metabolism
(associated with a slow component for
O2), from decreases in muscle
and plasma [HCO3]
consequent to buffering of lactic acid, and from release of
CO2 from the lung and tissue
CO2 stores by hyperventilation
(32). The MRT for heavy-intensity exercise (Table 3) demonstrated a
slowing of CO2 kinetics in
Acz compared with Con. This slowing of
CO2 kinetics during exercise
>ET in Acz may be expected as
additional CO2 is released from
stores consequent to a potentiated compensatory hyperventilation in Acz (i.e., greater E and
E/CO2
in Acz) that accompanies heavy-intensity exercise. The slowed
CO2 kinetics and lower
Amp2 during the on-transition in
Acz reinforces the observation that
CO2 elimination is impaired during
the early transition to the higher work rate.
Ventilatory response during moderate- and heavy-intensity
exercise.
Although E was similar between
conditions during loadless pedalling,
E/CO2
was higher during Acz compared with Con, suggesting that there was an
additional stimulus to breathe. In addition, end-exercise
E was higher in the Acz studies during both moderate- and heavy-intensity exercise, consistent with previous studies (20, 22, 24). Although it is generally held that CA inhibition
stimulates E by the metabolic acidosis
that develops from the renal excretion of sodium bicarbonate (17), it
is possible that CO2 retention in
the tissues also stimulates E (6). It is
not possible from the results of the present study to discriminate between possible ventilatory stimuli or the sites of action. However, given that an accommodation of only 30 min followed the Acz
administration, renal bicarbonate loss would not be significant,
although sufficient time would be available for a tissue respiratory
acidosis to develop.
E kinetics at the onset of
moderate-intensity exercise were slowed in Acz in contrast to the
faster E kinetics reported during an
NH4Cl-induced metabolic acidosis
(18). The carotid bodies are considered the primary mediators of the
compensatory hyperventilation associated with the metabolic acidosis
accompanying heavy-intensity exercise (16, 19, 35, 37) and of the
kinetics during the on-transient (phase
2) response to step increases in exercise intensity
(16, 35). Previous studies have shown that, under conditions of
increased carotid body gain such as induced metabolic acidosis (18) or
hypoxia (10, 11, 30), E kinetics are
speeded. Conversely, reducing carotid body gain by induced metabolic
alkalosis (18), hyperoxia (10, 11, 30), or carotid body resection (35)
results in slowed E kinetics. For
exercise <ET, phase
2 kinetics for E and
CO2 were isolated by applying the model to the response after phase
1 (Table 2). The slowed E during CA inhibition suggests that
the carotid body gain was affected by Acz administration. Evidence from
animal (12, 13, 26, 27) and human (23, 28) studies suggests that CA
inhibition affects carotid body activity, but the response in humans
during the non-steady-state exercise is presently not known. Although
the slowing of E kinetics during the
moderate-intensity exercise after CA inhibition is consistent with
altered carotid body activity, this effect cannot be discriminated from
the possible effects of the slowed
CO2 response that also
occurred with CA inhibition (discussed in Interaction
between CO2 and E kinetics during moderate-intensity
exercise).
A surprising finding in the present study was the speeding of
E kinetics during exercise
>ET after the administration of Acz
compared with Con. The mechanism responsible for the faster E kinetics is unclear and is particularly
difficult to reconcile given the slowing of
E kinetics during exercise
<ET. However, the heavy-intensity
exercise bouts were performed ~60 min after the infusion of Acz
(i.e., after 2 bouts of <ET exercise),
which may have potentiated the response of the central chemoreceptors. This hypothesis is speculative, but the issue does warrant further investigation, because Rausch et al. (19) suggested previously that a
central chemosensory mechanism was responsible for a slowly developing
ventilatory compensation during heavy-intensity, constant-load exercise.
Interaction between CO2
and E kinetics during moderate-intensity
exercise.
During the on-transition to moderate-intensity exercise, both
CO2 and
E kinetics were slowed during Acz
compared with during Con. Despite the inability to clearly define a
control mechanism, considerable evidence has been reported to suggest that E kinetics are mediated by the flow
of CO2 to the lungs (5, 31, 33,
34, 36). By using controlled volitional hyperventilation to lower body
CO2 stores before the onset of exercise, Ward et al. (31) demonstrated a slowing of
CO2 kinetics and a consequent
slowing of E kinetics. In the present
study, CA inhibition resulted in a higher
E/CO2
and lower PETCO2 at rest.
Thus, similar to the previous study (31), lowering of the body
CO2 stores before exercise may in
part explain the slower CO2
kinetics and, subsequently, the slower E
kinetics found in this study. Although this possibility cannot be
discounted, this effect would not be expected to contribute
significantly to the slowing of either
CO2 or
E because
PETCO2 was only ~3 Torr
lower during Acz than Con. This may be compared with the marked
decrease in PETCO2 of
10-15 Torr after hyperventilation in the study of Ward et al.
(31). As already discussed, the slower
CO2 kinetics during
moderate-intensity exercise appear to be associated with a
direct effect of CA inhibition on tissue
CO2 retention,
CO2 transport, and/or
CO2 reaction kinetics (at either
the muscle or lung) and not by a substantial unloading of
CO2 stores by an Acz-induced hyperventilation.
Summary.
The acute inhibition of CA with Acz was associated with a slowing of
CO2 kinetics during whole
body, constant-load exercise performed below and above the
ET. This slowing of
CO2 kinetics may be a
consequence of greater tissue CO2
retention and/or slowed equilibration of
CO2 in the blood and across the
pulmonary capillaries after CA inhibition. The mechanism for the slowed
elimination of CO2 during the
on-transient to exercise is yet unknown. During exercise
<ET, E
kinetics were slowed in the Acz studies, adding further support to the
close coupling observed between E and CO2. However, the possibility
that an attenuation of carotid body activity contributed to the slowing
of E kinetics, independent of
CO2, warrants further
investigation. That speeding of E
kinetics during exercise >ET may
reflect an increase in central chemoresponsiveness associated with
tissue CO2 retention also warrants investigation.
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ACKNOWLEDGEMENTS |
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The authors thank the participants who took part in this study. The technical support offered by Brad Hansen was greatly appreciated.
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FOOTNOTES |
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Financial support was provided by an operating grant from the Natural Sciences and Engineering Research Council of Canada. B. W. Scheuermann was supported by an National Sciences and Engineering Research Council Graduate Scholarship.
This research was carried out at The Centre for Activity and Ageing (affiliated with the Faculty of Health Sciences, School of Kinesiology, and the Faculty of Medicine at The University of Western Ontario and The Lawson Research Institute at the St. Joseph's Health Centre).
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. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: J. M. Kowalchuk, School of Kinesiology, 3M Centre, The Univ. of Western Ontario, London, Ontario, Canada N6A 3K7 (E-mail: jkowalch{at}julian.uwo.ca).
Received 15 May 1998; accepted in final form 12 January 1999.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Beaver, W. L.,
N. Lamarra,
and
K. Wasserman.
Breath-by-breath measurement of true alveolar gas exchange.
J. Appl. Physiol.
51:
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) and control (Con; 
) sessions. Vertical
dotted line indicates onset of transition from loadless cycling to
either moderate- or heavy-intensity exercise. Preinfusion (Pre),
postinfusion (Pos), and loadless cycling (0 W) values are presented
with exercise response.
