Vol. 90, Issue 4, 1431-1440, April 2001
Intermittent hypoxia increases ventilation and
SaO2 during hypoxic exercise and hypoxic
chemosensitivity
Keisho
Katayama1,
Yasutake
Sato1,
Yoshifumi
Morotome1,
Norihiro
Shima1,
Koji
Ishida1,
Shigeo
Mori2, and
Miharu
Miyamura1
1 Research Center of Health, Physical Fitness and Sports,
and 2 Space Medicine Research Center, Research Institute of
Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan
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ABSTRACT |
The
purpose of this study was 1) to test the hypothesis that
ventilation and arterial oxygen saturation (SaO2)
during acute hypoxia may increase during intermittent hypoxia and
remain elevated for a week without hypoxic exposure and 2)
to clarify whether the changes in ventilation and SaO2
during hypoxic exercise are correlated with the change in hypoxic
chemosensitivity. Six subjects were exposed to a simulated altitude of
4,500 m altitude for 7 days (1 h/day). Oxygen uptake
(
O2), expired minute ventilation (E), and SaO2 were measured during
maximal and submaximal exercise at 432 Torr before (Pre), after
intermittent hypoxia (Post), and again after a week at sea level
(De). Hypoxic ventilatory response (HVR) was also determined.
At both Post and De, significant increases from Pre were found in HVR
at rest and in ventilatory equivalent for O2
(E/O2) and
SaO2 during submaximal exercise. There were significant correlations among the changes in HVR at rest and in
E/O2 and
SaO2 during hypoxic exercise during intermittent hypoxia. We conclude that 1 wk of daily exposure to 1 h of
hypoxia significantly improved oxygenation in exercise during
subsequent acute hypoxic exposures up to 1 wk after the conditioning,
presumably caused by the enhanced hypoxic ventilatory chemosensitivity.
hypoxic ventilatory response; hypercapnic ventilatory response; altitude; arterial oxygen saturation
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INTRODUCTION |
SEVERAL STUDIES HAVE
INDICATED that hypoxic and hypercapnic ventilatory responses (HVR
and HCVR, respectively), as indexes of ventilatory chemosensitivity to
hypoxia and hypercapnia, correlate with ventilatory response to
exercise in normoxia (16, 29, 39, 45) and that HVR
correlates with ventilation and arterial oxygen saturation
(SaO2) during hypoxic exercise (8,
45). Also, it has been reported that chronic exposure to
hypoxia and sojourns at high altitude lead to increases in resting HVR
accompanied by increases in pulmonary ventilation and
SaO2 at rest and during exercise in hypoxia (5,
18, 32, 46, 51, 56).
Similar to chronic exposure to hypoxia or a sojourn at high altitude,
intermittent exposure to hypoxia with or without endurance exercise
training using a hypobaric chamber has been utilized for
preacclimatization before climbing to high altitude (9, 43,
44). When combining intermittent exposure to hypoxia
with endurance exercise training, increases in HVR have been
demonstrated in some (9, 21, 27) but not other
(19) studies. However, there are few reports that have
shown the changes in cardiorespiratory acclimatization during
intermittent hypoxic exposure without endurance training. We previously
found that resting HVR increased after short-term intermittent hypoxic
exposure without endurance training (19). However, in that
study, because we were unable to measure ventilation and
SaO2 during hypoxic exercise after intermittent hypoxia, it is unclear whether alterations of ventilation and SaO2 during hypoxic exercise
accompany the change in HVR.
Although the cardiorespiratory adaptations for altitude acclimatization
have been reported by many investigators as mentioned above,
physiological responses during deacclimatization have received little
attention. Moreover, the measurements during deacclimatization have
generally been performed only at low altitude. To elucidate the changes
in cardiorespiratory response to hypoxic exercise during
deacclimatization, Beidleman et al. (5) measured
cardiorespiratory parameters during hypoxic exercise before and after
acclimatization to high altitude for 18 days (chronic hypoxic exposure)
and 8 days after returning to sea level. They observed that a large degree of exercise responses associated with acclimatization was retained with reintroduction to altitude after 8 days at sea level [i.e., increases in ventilation and SaO2 and
a decrease in heart rate (HR)]. However, there are no available data
concerning the influence of deacclimatization after intermittent
hypoxic exposure on physiological responses in humans, except our
previous study that indicated that increased HVR after 6 days of
intermittent hypoxia was retained for 1 wk (19). If HVR is
related to exercise ventilation and SaO2 in hypoxia as
proposed by previous studies (8, 45, 46), it is possible
to hypothesize that increases in ventilation and SaO2
during hypoxic exercise occur during short-term intermittent hypoxia
without endurance training and that increased ventilation and
SaO2 during hypoxic exercise after intermittent hypoxic exposure may also be retained for at least 1 wk.
The primary purpose of this study, therefore, was to test the
hypothesis that ventilation and SaO2 during hypoxic
exercise may increase after short-term intermittent hypoxia and that
these increases may remain for a week without hypoxic exposure. The secondary purpose was to clarify whether the changes in ventilation and
SaO2 during hypoxic exercise are correlated with the
change in resting ventilatory chemosensitivity. For this purpose, we determined cardiorespiratory parameters during hypoxic exercise and
resting ventilatory response to hypoxia and hypercapnia at sea level
before and after intermittent hypoxic exposure.
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METHODS |
Subjects.
Six healthy men with no history of cardiorespiratory diseases
volunteered to participate in this study. Their physical
characteristics are shown in Table 1. The
subjects were informed of the experimental procedures and possible
risks involved in the present study, and their informed consent was
obtained. This study was approved by the Human Research Committee of
the Research Center of Health, Physical Fitness and Sports of Nagoya
University.
Experimental procedures.
The time course of experimental procedures in the present study is
presented in Fig. 1. Subjects were
familiarized with the equipment used in this experiment at sea level
and the hypobaric chamber. Before the intermittent exposure to altitude
(Pre), the maximal exercise test was conducted at sea level (Fig. 1).
The measurements of resting ventilatory chemosensitivity at sea level and maximal and submaximal exercise tests at 432 Torr in the hypobaric chamber (simulating an altitude of 4,500 m) were performed at P1 and P2
(Fig. 1), respectively (resting ventilatory chemosensitivity tests were
always made before the exercise test). The same hypobaric chamber used
in our previous studies (19-21) was utilized for the exercise test and for intermittent hypoxic exposure. The barometric pressure in the chamber was lowered to 432 Torr over a 30-min period
and then held at that level for the next hour. For the maximal and
submaximal exercise tests, the testing began within the first 0.5 h at 432 Torr. The subjects completed the self-assessment portion of
the Lake Louise Consensus Questionnaire (15) each day
doing the 7-day intermittent hypoxic exposure (D1 to D7, Fig. 1). The
measurements of resting ventilatory chemosensitivity at sea level and
the maximal and submaximal exercise tests at 432 Torr were performed
after the intermittent hypoxic exposure (Post; D8 and D9). These
measurements were taken again after the subjects had been away from
hypoxic exposure for 1 wk (De; D15 and D16) as shown in Fig. 1.
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Fig. 1.
Time course of the experiment. The measurements were performed
before (Pre; P1 and P2) and after (Post; D8 and D9) intermittent
hypoxia and again after 1 wk without hypoxic exposure (De; D15 and
D16). HVR, hypoxic ventilatory response; HCVR, hypercapnic ventilatory
response using the CO2-rebreathing method;
HCVRSB, hypercapnic ventilatory response using the
single-breath CO2-rebreathing method.
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Maximal exercise test.
Maximum oxygen uptake (O2 max) at sea
level in each subject was determined only at Pre. The
O2 max at 432 Torr in a hypobaric
chamber was measured at Pre (P1), Post (D8), and again at De (D15) as
shown in Fig. 1. The measurement of
O2 max was conducted the same way as in
our previous study (20). To measure
O2 max, an incremental protocol on an
electromechanically braked bicycle ergometer was used at sea level and
a mechanically braked bicycle ergometer (Monark) was used in the
chamber. The maximal exercise test began at an initial power output of
60 W, and the workload was increased 30 W every 2 min until exhaustion. The pedaling rate was kept constant at 60 rpm with the aid of a
metronome. During the test, expired gases were collected into a Douglas
bag during the last 30 s of each intensity level until exhaustion.
Expired minute ventilation (E, BTPS) was
measured with a wet-gas meter (model 10 liter, Shinagawa). Gas
analysis was performed by means of an O2 and
CO2 analyzer (model MG-360, Minato Ikagaku). HR was
continuously recorded by a three-lead electrocardiogram (model
OEC-6401, Nihon Koden) throughout the test.
SaO2 was measured by a finger pulse
oximeter (model OLV-1200, Nihon Koden) throughout the test in the
depressurized chamber. The accuracy of SaO2 estimated
by this oximeter has been proven by a previous study that compared
SaO2 assessed by the OLV-1200 with that determined
directly from arterial blood (2). The maximal minute
ventilation (Emax) and the maximal HR
value (HRmax) were also measured. Oxygen uptake
(O2) derived during maximal exhaustive
exercise was considered to be O2 max
when two of the following three criteria were satisfied: identification of a plateau in O2 with an increase in
power output (<150 ml O2 increase),
HR ± 10% of age-predicted maximum (220 
age), and
respiratory exchange ratio (RER) 
1.0 (7, 20).
Submaximal exercise test.
O2 in each subject during the submaximal
exercise test was determined at Pre (P2), Post (D9), and De (D16) at
432 Torr in a hypobaric chamber as shown in Fig. 1. Before the
submaximal exercise test, O2, carbon
dioxide output (CO2),
E, HR, and SaO2 at rest were
measured at 432 Torr in the chamber. Then, each subject exercised using
the bicycle ergometer at 40% of his
O2 max at altitude for the first 10 min
and 70% of his O2 max at altitude from
the 10th to the 20th min at 432 Torr (each intensity was calculated by
O2 max at 432 Torr on each preceding day). HR and SaO2 were measured throughout the
submaximal exercise test, and the mean value was obtained during the
last minute of each exercise level. Expired gases were collected in a
Douglas bag during the last minute of each exercise intensity, and
O2, CO2,
RER, and E were determined using the same system as
in the maximal exercise test mentioned above.
HVR.
HVR measurements were performed at P1, D8, and D15 at sea level (Fig.
1). Resting HVR was determined by using a progressive isocapnic hypoxic
test (54). A rebreathing system similar to that in our
previous studies (19-21) was used. Tidal volume
(VT), inspired minute ventilation (I),
end-tidal CO2 and O2 fraction (FETCO2 and
FETO2, respectively), and
SaO2 were measured continuously during rebreathing.
The subjects breathed through a mouthpiece attached to a hot-wire
flowmeter (model RF-H, Minato Ikagaku). Sample gas was drawn through a
sampling tube connected to the mouthpiece to measure
FETCO2 and
FETO2 by using gas analyzer (model MG-360,
Minato Ikagaku), and end-tidal partial pressure of CO2 and
O2 (PETCO2 and
PETO2, respectively) were calculated from
FETCO2 and
FETO2.
PETCO2 was maintained within ±2 Torr of
the resting level during measurement. SaO2
was measured by means of a finger pulse oximeter (model OLV-1200, Nihon
Koden). The signals from the flowmeter, gas analyzer, and pulse
oximeter were sampled at a frequency of 100 Hz through an
analog-to-digital converter (model ADX-98H, Canopus) and stored in a
computer (model PC-9821XA, NEC). HVR was estimated as the slope of the
line calculated by the linear regression relating I
to SaO2
(
I/SaO2, where is change; in l · min
1 · %1), and the
slope was presented as positive numbers by convention. In
addition, HVR was also assessed by the slope factor (A,
l · min1 · Torr1) for the
I-PETO2 curve
(54): I = Vo + A/(PETO2 32), where I is in liters per minute (l/min); Vo is
the asymptote for ventilation obtained by extrapolation; and 32 is the
asymptote for PETO2 in Torr when
I is infinite.
HCVR.
To assess central and peripheral chemosensitivities to
hypercapnia, resting HCVR was determined by two methods: the
CO2-rebreathing (HCVR) and the single-breath
CO2 (HCVRSB) methods. The measurements of HCVR
and HCVRSB were also similar to that of our previous study (20). HCVR measurements were determined at P1, D8, and D15
at sea level, whereas HCVRSB measurements were performed at
P2, D9, and D16 (Fig. 1). In the rebreathing method, subjects
rebreathed a gas mixture of 7% CO2 in O2 from
a bag (5-6 liters) in a plastic box for 3-4 min
(38). I and
PETCO2 were recorded in the same computer used in the HVR test. HCVR was assessed as the slope of the
line determined by the linear regression relating
PETCO2 to I
(I/PETCO2;
in
l · min1 · Torr1).
On the other hand, the single-breath CO2 test was used for the evaluation of peripheral chemoreceptor response to CO2
(HCVRSB) according to the protocol described by McClean et
al. (31); i.e., application of a single CO2
mixture composed of 13% CO2-21% O2-66%
N2 was repeated six to eight times with 2- to 3-min
intervals for each subject. The apparatus consisted of a bag-in-box
circuit similar to that used for the CO2-rebreathing test.
The subjects were seated comfortably in a chair and began breathing
room air through a mouthpiece with a nose clip. The T valve was
attached between the bag and the mouthpiece, and the port was connected to either room air or a the bag containing the test gas. To avoid the
possibility that the maneuver for administering the different gases was
noticed by the subjects, a screen was placed between the subject and
the T valve. During testing, VT, I,
FETCO2, FETO2, and inspiratory time
(TI) were recorded continuously. When stable levels of
FETCO2 and VT had been
achieved, the inspiratory gas was switched from room air to the bag for
a single tidal breath by turning the T valve during the expiratory
phase of the previous breath. During the expiratory phase of the test
breath, the T valve was turned back again to the first air position.
Data for analyzing HCVRSB were limited to breaths within
the first 20 s, after transients of hypercapnia, to exclude
contribution of the central CO2 chemoreceptors to the
response. HCVRSB was quantitated in a manner similar to
that suggested by Khoo (22) (and expressed in units of
ml · s1 · Torr1): first,
the changes in VT/TI
(VT/TI) and
PETCO2
(PETCO2) for a given breath after
individual transients was computed; second, PETCO2 was corrected by means
of correction formula by Khoo; then the six to eight measurements of
VT/TI and
PETCO2 were averaged, respectively; and
finally, the averaged VT/TI was divided by
the averaged PETCO2 to assess the
(VT/TI)/PETCO2
for each subject.
Statistical analysis.
Values are expressed as means ± SD. The changes in all parameters
during the experimental periods were analyzed using one-way ANOVA with
repeated measurements. Differences in the parameters at each session
(Pre, Post, and De) were determined by using the Tukey's honestly
significant difference test. The relationships among the
parameters were determined by simple linear regression analysis. The
SPSS statistical package was used for these analyses. The level of
significance was set at 0.05.
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RESULTS |
Baseline descriptive data.
Table 1 indicates O2 max,
Emax, and HRmax at
exhaustion during the maximal exercise test at sea level before
intermittent hypoxic exposure. At D1 and D2 of intermittent hypoxic
exposure, two of the subjects had slight headaches, fatigue, and/or
weakness at 432 Torr, but thereafter there was a score of zero for the Lake Louise Consensus Questionnaire for intermittent hypoxic exposure.
Maximal exercise test.
Table 2 and Fig.
2A demonstrate
that there were no changes in
O2 max,
CO2 max,
Emax, ventilatory equivalent for
O2
(E/O2), RER, and
HRmax determined at 432 Torr throughout the experimental
periods. On the other hand, SaO2 at exhaustion at 432 Torr increased significantly (P < 0.05) at Post (D8) and remained at that level at De (D15) as shown in Fig. 2B.
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Table 2.
Cardiorespiratory responses at rest, at 40 and 70% of
O2max, and at exhaustion at 432 Torr in a hypobaric chamber before, after, and 1 wk after
intermittent hypoxic exposure
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Fig. 2.
Ventilatory equivalents for O2 [expired
minute ventilation (E)/oxygen uptake
(O2); A] and arterial oxygen
saturation (SaO2; B) at rest, at
40 and 70% of O2 max, and at
exhaustion (max) at 432 Torr measured at Pre, Post, and De. Values are
means ± SE. *Significantly different from Pre, P < 0.05.
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Submaximal exercise test.
Cardiorespiratory parameters obtained at rest and during the submaximal
exercise test in the hypobaric chamber are presented in Table 2 and
Fig. 2.
At rest in the chamber at 432 Torr, O2,
CO2, RER, and HR did not show any
changes at Pre (P2), Post (D9), and De (D16). Resting
E and
E/O2 at 432 Torr
increased significantly (P < 0.05) at Post, and they
remained at that level at De. Similarly, resting SaO2
at 432 Torr showed a significant (P < 0.05) increase at Post compared with that at Pre, and it remained at that level at De
as shown in Fig. 2B.
O2 and workload did not show
significant changes at Pre, Post, and De at both 40 and 70% of
O2 max exercise levels (Table 2).
E and
E/O2 at Post
increased significantly (P < 0.05) at 40 and 70% of
O2 max levels compared with those at
Pre, and these variables remained at those levels at De (Table 2, Fig.
2A). As shown in Fig. 2B, SaO2
at 40 and 70% of O2 max also showed
significant (P < 0.05) increases at Post, and these
increased levels of SaO2 were retained at De. CO2, RER, and HR did not change at 40 and 70% of O2 max throughout the
experimental period (Table 2).
HVR.
Tested at sea level, resting I, respiratory
frequency (f), PETO2, and
PETCO2 did not show any changes throughout
the experimental period as shown in Table
3. Figure
3A indicates the
changes in the I/SaO2. A
significant (P < 0.05) increase in the
I/SaO2 (l · min1 · %1) was found
at Post, and the increased i/SaO2
remained at De. A of the
I-PETO2 curve also
increased at Post and De compared with that at Pre [113.9 ± 50.6 (Pre), 195.7±83.9 (Post), and 191.5 ± 88.3 (De)
l · min1 · Torr1].
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Fig. 3.
HVR (A), HCVR (B), and
HCVRSB (C) at sea level measured at Pre, Post,
and De. *Significantly different from Pre, P < 0.05.
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HCVR.
There was no significant change in HCVR throughout the
experimental period as shown in Fig. 3B.
HCVRSB.
As shown in Fig. 3C, HCVRSB increased
significantly (P < 0.05) after intermittent hypoxic
exposure for 7 consecutive days (Post). However, a significant loss of
HCVRSB occurred 1 wk later (De).
Relationships among parameters during intermittent hypoxic
exposure.
Table 4 presents the correlation matrix
among absolute values of resting HVR at sea level and
E/O2 and
SaO2 at rest and during exercise at 432 Torr at Pre
and Post. There were significant correlations among HVR at rest,
E/O2 and
SaO2 at rest and during submaximal exercise at 432 Torr, but not among HVR at rest, E/O2 and
SaO2 during maximal exercise. There were no
significant relationships between HCVR or HCVRSB at rest
for either E/O2 or
SaO2 at rest or during exercise in hypoxia.
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Table 4.
Correlation matrix among absolute values of resting HVR at sea level
and the E/O2 and
SaO2 at rest and during exercise at 432 Torr at Pre
and Post
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To compare among parameters during intermittent hypoxia in detail, the
magnitude of changes in
E/O2 and
SaO2 at rest and during exercise
(
E/O2 and
SaO2) at 432 Torr and resting ventilatory responses
to hypoxia (HVR) and hypercapnia (HCVR and HCVRSB)
at sea level were calculated individually as the difference between
those obtained before and after intermittent exposure to altitude ( = Post Pre). Significant correlations were observed among
HVR, E/O2, and
SaO2 at rest and at 40 and 70% of
O2 max exercise as shown in Table
5. However, no significant correlations
among HVR,
E/O2, and
SaO2 at exhaustion were found. There were no
significant relationships between HCVR or HCVRSB for
either E/O2 or
SaO2 at rest or during exercise in the hypobaric
chamber during intermittent hypoxic exposure.
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Table 5.
Correlation matrix among the change in resting HVR at sea level, the
changes in E/O2,
and SaO2 at rest and during exercise at 432 Torr
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DISCUSSION |
In the present study, we found that 1) ventilation and
SaO2 at rest and during exercise at light and moderate
levels at 432 Torr in the hypobaric chamber (equivalent to 4,500 m
altitude) increased significantly after 1 wk of intermittent hypoxic
exposure; 2) increased ventilation and SaO2
at rest and during submaximal exercise in hypoxia remained stable at
this increased level for 1 wk after cessation of hypoxic exposure;
3) HVR and HCVRSB also showed significant
increases after intermittent hypoxic exposure and increased HVR
remained for 1 wk, whereas HCVRSB did not; 4) HCVR did not change after intermittent hypoxic exposure; and
5) significant correlations exist among absolute values of
E/O2 and
SaO2 at 40 and 70% of
O2 max exercise at 432 Torr and HVR at
sea level and among
E/O2 and
SaO2 during submaximal exercise at 432 Torr and
HVR during intermittent hypoxic exposure, respectively.
Acclimatization to intermittent hypoxia.
The earliest and most obvious response and adaptation of the sojourner
to high altitude is an increase in ventilation (4, 7, 32, 35,
51), accompanied by hypocapnia and elevating alveolar and
arterial oxygenation. This increasing ventilation in hypoxia may be
advantageous for performance at altitude and prevents acute mountain
sickness and high-altitude pulmonary edema (23, 33, 46).
It is also well known that HVR, as an index of ventilatory
chemosensitivity to hypoxia, increases during varying durations of
continuous stays at altitude (11, 42, 47, 55) and that HVR
at sea level is closely related to ventilation and SaO2 during hypoxic exercise and performance at high
altitude (8, 30, 45, 46). As described previously,
Schoene et al. (46) studied the relationships among HVR at
sea level, exercise ventilation, and O2 saturation during
acclimatization to high altitude. They indicated that HVR at sea level
positively correlated with ventilation during exercise at altitude
after acclimatization and suggested that a high HVR is one of the
factors that minimizes O2 desaturation at high altitude
during acclimatization. Although there are many studies that have
reported respiratory and cardiovascular responses during chronic
hypoxic exposure or sojourns at altitude, the effects of intermittent
exposure to altitude on cardiorespiratory parameters at rest and during
exercise have had little attention. In our previous study
(19), it was revealed that intermittent hypoxic exposure
for 6 consecutive days elicited an increase in HVR at sea level. Thus
we hypothesized that intermittent exposure to hypoxia for a short
period also leads to increases in ventilation and SaO2
during hypoxic exercise as well as chronic hypoxic exposure as
demonstrated by Schoene et al (46). One of the purposes of the present study was to test this hypothesis.
After intermittent hypoxic exposure for 1 wk,
O2 max at 432 Torr did not change
throughout the experiment (Table 2). This result concurs with the data
showing that either chronic (5, 32, 51, 56, 57) or
intermittent (40) exposure to altitude showed no effect on
O2 max in hypoxia. Because O2 at 40 and 70% of
O2 max at 432 Torr also did not change
at Pre, Post, and De as shown in Table 2, it is possible to compare
cardiorespiratory responses during hypoxic exercise throughout the
experimental period.
During acclimatization to high altitude, an increase in ventilation at
rest has been well reported by numerous studies that used chronic
(4, 7, 18, 35) or intermittent hypoxic exposure (36,
43). In the present study, our data agree with these prior
reports in which intermittent hypoxic exposure led to an increase in
E/O2 at rest at 432 Torr as shown in Fig. 2A.
E/O2 at 40 and 70%
of O2 max exercise workloads also
increased significantly (P < 0.05) after 7 days of
intermittent hypoxic exposure (Post) as we had expected.
E/O2 at exhaustion in
a hypobaric chamber tended to increase, but not significantly, after
intermittent hypoxic exposure (Post) (Fig. 2A). Savourey et
al. (43) reported that exercise ventilation at light or
moderate levels at 4,500 m increased significantly after intermittent
exposure to altitude. In addition, other studies have shown that
exercise ventilation at a modest level of exercise and at exhaustion
was elevated after chronic exposure to high altitude (4, 5, 7,
32, 57). These observations are in agreement with those of the
present study. Overall, these results suggest that short-term intermittent hypoxic exposure also leads to increases in ventilation at
light and moderate exercise levels in hypoxia as well as chronic hypoxic exposure.
Resting ventilation at 432 Torr increased significantly after
intermittent hypoxia, whereas resting I, f,
PETO2, and
PETCO2 at sea level did not
change as shown in Table 3. It has been demonstrated that an increase
in E and a decrease in
PETCO2 persist on return to sea level
after an altitude sojourn (4, 35). In contrast, several
studies have indicated that resting E,
PETO2,
PETCO2, and pH did not show any changes
after intermittent hypoxic exposure (20, 27, 48). These
results are in agreement with those of the present study. Therefore, we
suggest that short-term intermittent hypoxic exposure does not change
oxygenation and acid-base balance at sea level. Thus it is likely that
chemoreceptors were at comparable levels for each chemosensitive test
at sea level throughout the experimental period.
It has hitherto been reported that resting HVR increases during chronic
exposure to hypoxia (11, 35, 41, 42). When combining
intermittent hypoxia with endurance exercise training, some studies
have indicated increases in HVR (9, 21, 27), whereas
others have not (19, 20). However, without endurance training, there are only a few reports that have demonstrated the
changes in ventilatory chemosensitivity during intermittent hypoxia in
humans: both our previous study (19) and Serebrovskaya et
al. (48) reported that resting HVR at sea level increased significantly after short-term intermittent hypoxic exposure. A
significant increase in HVR was also found in the present study (Fig.
3A), suggesting that short-term intermittent exposure to high altitude, without exercise training, certainly induces an increase
in ventilatory sensitivity to hypoxia. In the present study, we used
the resting PETCO2 level for isocapnic HVR
testing at sea level. If resting ventilation and
PETCO2 at sea level had changed after
intermittent hypoxia, the resting PETCO2
would not have been proper for isocapnic HVR testing at sea level.
However, as mentioned above, resting I and
PETCO2 at sea level did not change
subsequently throughout the experiment. Thus it does seem reasonable to
suppose that resting the PETCO2 level for
isocapnic HVR testing at sea level in this study was appropriate and
that the changes in HVR reflect the changes in the actual ventilatory sensitivity to hypoxia.
In addition to HVR, it has been shown that HCVR increases during
sojourns at altitude or chronic exposure to hypoxia (10, 35, 42,
47, 55). To our knowledge, the effect of intermittent exposure
to hypoxia on HCVR has not been demonstrated in the literature, except
for our previous study, which reported no increase in HCVR (19). In the present study, there was also no change in
the slope of HCVR after intermittent hypoxic exposure (Fig.
3B). Separation of peripheral and central contributions to
the ventilatory response to hypercapnia is arduous (14).
Although the ventilatory response to hypercapnia by means of the
hyperoxic CO2-rebreathing method includes a contribution
from peripheral chemoreceptors, it is considered to be a response
mediated primarily through the central chemoreceptors. Thus it may be
that short-term intermittent exposure to high altitude does not elicit
an increase in central hypercapnic chemosensitivity.
On the other hand, several investigators have proposed that a single
breath of hypercapnic gas mixture is a useful method for evaluating
sensitivities of peripheral chemosensitivity to hypercapnia, and, by
using this method, ventilatory response mediated through the peripheral
chemoreceptors can be studied independently of actions of the stimuli
on the central chemoreceptors (13, 14, 31). However, a few
investigators have indicated that peripheral hypercapnic
chemosensitivity increases during sojourns at high altitude (25,
37). Thus we hypothesized that intermittent exposure to altitude
may also lead to an increase in peripheral chemoreceptor responsiveness
to hypercapnia. It is of interest that HCVRSB increased
significantly after intermittent exposure to altitude as shown in Fig.
3C. Although the reasons for the discrepancies between HCVR
and HCVRSB after intermittent hypoxia are unclear, these
results suggest that hypercapnic chemosensitivity may be changeable
more in the peripheral than in the central during intermittent hypoxic
exposure for short periods.
Indeed, centrally mediated influences are included in the HVR
determined by the progressive isocapnic hypoxic test, but hypoxic stimuli undoubtedly have a predominant peripheral chemoreceptor component (14). Some studies have demonstrated that the
results of a single-breath CO2 test do not correlate with
those of the hypoxic test (10, 20, 24). These results
suggest that it is possible to distinguish between the peripheral
chemoreceptor responses to hypoxia and hypercapnia (34).
Moreover, McClean et al. (31) have proposed that the
presence of a peripheral CO2 response does not necessarily
prove the presence of a hypoxic response in the same subject, given
that the two mechanisms are interdependent. In the present study, both
HVR and HCVRSB increased significantly at Post, but there
was no statistically significant correlation between absolute values of
HVR and HCVRSB at Pre or Post, or between the individual
changes in HVR and HCVRSB during intermittent hypoxia.
Therefore, these results suggest that there may be at least partially
separate pathways of increased peripheral chemoreception for
O2 and CO2 stimuli during intermittent hypoxic exposure.
A number of studies have indicated that there is a significant
relationship between resting ventilatory chemosensitivity and the
ventilatory response to exercise in normoxia or hypoxia (8, 28,
29, 39, 45). However, as far as we know, only one study
performed simultaneous measurements of HVR and exercise ventilation in
hypoxia during acclimatization; i.e., Schoene et al. (46)
reported that at light and moderate levels of exercise, exercise
ventilation during hypoxia after chronic exposure to high altitude was
correlated to resting HVR. In the present study, there were significant
(P < 0.05) positive correlations between absolute values of
HVR at sea level and
E/O2 at both 40 and 70% of O2 max at 432 Torr (Table 4)
and between HVR at sea level and
E/O2 during
submaximal exercise at 432 Torr during intermittent hypoxia (Table
5). These results indicate that the increased exercise
ventilation at light and moderate levels at 432 Torr after intermittent
hypoxic exposure could be primarily the result of an increase in
ventilatory chemosensitivity to hypoxia. On the other hand, a
significant relationship both between HVR and
E/O2 at exhaustion in
hypoxia (Table 4) and between HVR and
E/O2 at exhaustion
was not found during intermittent hypoxia (Table 5). Schoene
(45) also observed that ventilation at high-intensity
exercise at altitude did not correlate to HVR at sea level and
suggested that possibly other factors, e.g., potassium and lactic acid,
influence exercise ventilation at a high level of exercise in hypoxia.
Thus it is possible to assume that these factors, rather than hypoxic
chemosensitivity, may strongly affect ventilation at exhaustion in
hypoxia. Because these parameters were not measured during exercise in
the present study, however, it is necessary to confirm this assumption
by further study.
Resting SaO2 at 432 Torr after intermittent hypoxic
exposure increased significantly (P < 0.05) as shown
in Fig. 2B. This result is in agreement with those of
previous studies (4, 6, 19, 35, 43). Similarly, at all
exercise levels (at 40 and 70% of
O2 max, and at exhaustion) at 432 Torr,
SaO2 did show significant (P < 0.05)
increases after intermittent hypoxia (Fig. 2B), and these
data also coincide with those of studies that measured
SaO2 during exercise in continuous altitude hypoxic exposure (5-7, 32, 46, 51). From these data, we can
be fairly certain that SaO2, both at rest and during
hypoxic exercise, increases after intermittent exposure to
altitude, as well as after chronic exposure to altitude.
One methodological concern is the use of the pulse oximeter to measure
SaO2 because resting SaO2 at 432 Torr
(66.8 ± 6.4 Torr at Pre shown in Fig. 2B) obtained
here is lower than those in some studies (43, 53).
Although another study (26) indicated ~68%
SaO2 at 4,509 m and this does not differ from the
present study, we need to consider whether SaO2 values
in this study are accurate. The accuracy of the OLV-1200 has been
proven by Aoyagi (2), who described a high correlation
between the calculated SaO2 from arterial blood
samples and SaO2 estimated by the OLV-1200 (r
= 0.99; P < 0.0001, n = 52) with
a SE of estimate of 1.63% in SaO2 values from 47 to
99% for the OLV-1200. Judging from these data, we conclude that the
validity of the OLV-1200 pulse oximeter is sufficient to accurately
measure SaO2 and that the data collected using this
pulse oximeter are reliable.
As shown in Tables 4 and 5, there were statistically significant
(P < 0.05) relationships between absolute values of
E/O2 and
SaO2 at rest and at 40 and 70% of
O2 max at 432 Torr and between
E/O2 and
SaO2 at rest and during submaximal exercise at 432 Torr during intermittent hypoxia. These results indicate that increased
SaO2 at rest and at 40 and 70% of
O2 max at 432 Torr could be caused
primarily by increased pulmonary ventilation. On the other hand, no
significant relationship between
E/O2 and
SaO2 at exhaustion in hypoxia (Table 4) or
between E/O2 and
SaO2 at exhaustion was observed during intermittent
exposure to hypoxia (Table 5). Thus the increase in
SaO2 at exhaustion in hypoxia might not be explained
by the change in exercise ventilation. However, it has been
demonstrated that after acclimatization to altitude, cardiac output
falls at either maximal or submaximal exercise (1, 4, 17,
49-51, 56), and the lower blood flow can result in
increased transit time of the erythrocyte in the pulmonary capillary
(7). Prolongation of capillary transit time is likely to
allow a saturation increase (3, 52). Therefore, one of the
ways to explain increased SaO2 during hypoxic
exercise, either at maximal or submaximal levels, may be that falling
cardiac output after intermittent exposure to hypoxia induces longer
capillary transit time, although we did not measure this in the present study. Also, it is likely that hyperventilation during hypoxic exercise
led to respiratory alkalosis, resulting in the leftward shift of the
oxygen dissociation curve. This may explain the increased SaO2 after intermittent exposure to altitude (7,
46).
Schoene et al. (46) demonstrated that HVR correlates
positively with not only exercise ventilation but also
SaO2 during hypoxic exercise after acclimatization to
high altitude. They also concluded that resting HVR at sea level is an
important predictor of the degree of decrease in SaO2
at altitude. We also found positive significant (P < 0.05) relationships between absolute values of HVR at sea level and
SaO2 at 40 and 70% of
O2 max at 432 Torr (Table 4) and
between HVR at sea level and SaO2 during submaximal exercise at 432 Torr during intermittent hypoxia (Table 5).
These results suggest that the change in SaO2 during
submaximal exercise in hypoxia can be estimated by the change in
hypoxic ventilatory chemosensitivity measured at sea level during
intermittent hypoxic exposure as well as during chronic exposure.
Deacclimatization to intermittent hypoxia. To our knowledge,
cardiorespiratory responses at rest and to exercise during
deacclimatization have received little attention. In our previous
study, it was found that increased HVR at sea level after intermittent
exposure to hypoxia without exercise training for short periods was
retained for 1 wk (19). In the present study, retention of
HVR was also found at De (D15) as shown in Fig. 3A, and this
result confirms previous studies that indicated that elevated HVR after
intermittent or chronic exposure to altitude for short periods was
maintained 1 wk later (12, 19). In contrast, several
investigators demonstrated that a significant loss of HVR occurred
within 1 wk after a return to sea level (35, 41, 42). One
concern may be the validity of the HVR test, because it may be that the
increased HVR is not a result of the intermittent hypoxia but of the
repeated HVR testing. To verify the reliability of the HVR test in the
present study, we performed the test three times at 1-wk intervals in a
different group of six male volunteers without intermittent hypoxic
exposure (average values for age, height, body mass, and
O2 max were 23.8 ± 3.1 yr,
171.0 ± 5.3 cm, 64.0 ± 5.4 kg, and 55 ± 6.5 ml · kg1 · min1,
respectively, and these values were not significantly different from
those of the experimental group). The result was that there were no
changes in HVR during the three tests (0.68 ± 0.24, 0.67 ± 0.23, and 0.70 ± 0.21 l · min1 · %1). Thus it
seems reasonable to suppose that the values of HVR in the present study
are valid and that the elevated HVR after intermittent hypoxia obtained
here was not a result of the repeated testing. However, we are not
certain of the reasons, and these discrepancies between other
studies and the present one may be related to various factors such as
the differences in altitude, the procedure of hypoxic exposure, whether
it was chronic or intermittent, and the characteristics of the
subjects. Further research is required to elucidate this assumption.
Interestingly, increased ventilation at rest and during submaximal
exercise at 432 Torr remained at De as shown in Table 2 and Fig.
2A, and increased SaO2 at rest and at all
exercise levels at 432 Torr also remained at De (Fig. 2B),
as we had expected. As far as we know, this is the first observation on
the effects of deacclimatization on ventilatory and
SaO2 responses to hypoxic exercise after utilization
of intermittent hypoxia for short periods. These results concur with
those of Beidleman et al. (5), who reported that
cardiorespiratory responses to hypoxic exercise after a sojourn at
altitude for 16 days were retained after 8 days at sea level. On the
basis of these results, it seems reasonable to suppose that increased
ventilatory and SaO2 responses to hypoxic exercise
after short-term intermittent hypoxic exposure will be retained for at
least 1 wk.
In contrast to increased HVR at De, a significant loss of
HCVRSB, as an index of peripheral chemosensitivity to
hypercapnia, occurred at De as shown in Fig. 3C. Pande et
al. (37) demonstrated that chronic altitude exposure for 1 wk elicited an increase in peripheral hypercapnic chemosensitivity.
However, elevated peripheral hypercapnic chemosensitivity tended to
decrease to preexposure levels during the next week at altitude.
Therefore, peripheral hypercapnic chemosensitivity may be more
changeable than hypoxic chemosensitivity.
Numerous studies have found that arterial oxygenation and/or exercise
performance at moderate and high altitudes are related to HVR. Thus an
evaluation of HVR at sea level can be used as an indicator of a
climber's capability at high altitude (30, 46). A more
vigorous ventilatory response to hypoxia is beneficial for the
sojourner to avoid acute mountain sickness and may help performance at
moderate and extremely high altitude (23, 33, 45, 46). We
found in the present study that resting HVR at sea level and
SaO2 and ventilation during hypoxic exercise increased at Post, and these variables were retained at those levels at De.
Therefore, it is conceivable that increased SaO2 and
ventilation during submaximal exercise in hypoxia may improve
performance at both Post and De, although we did not evaluate endurance
performance, such as submaximal exercise endurance in hypoxia. Thus
further investigation is needed to clarify whether beneficial exercise response after intermittent hypoxic exposure is related to improvement of physical performance in hypoxia and to what extent it remains after
returning to sea level.
In conclusion, after an intermittent exposure to 432 Torr
(equivalent to 4,500 m altitude) in a hypobaric chamber for 1 wk, ventilation and SaO2 during submaximal exercise in
hypoxia increased significantly, and the changes in these variables
during submaximal exercise were related to the changes in the resting
HVR but not HCVR and HCVRSB. Also, increased ventilatory
and SaO2 responses to hypoxic exercise and elevated
HVR after intermittent hypoxic exposure were retained after 1 wk
without hypoxic exposure. The results from this study suggest that an
increase in ventilation during submaximal exercise in hypoxia, which is
accompanied by increases in SaO2, can be obtained by
using short-term intermittent hypoxic exposure and that the increased
ventilation and SaO2 during submaximal exercise in
hypoxia are presumably caused by the enhanced hypoxic ventilatory chemosensitivity.
| |
ACKNOWLEDGEMENTS |
We appreciate the cooperation of the subjects in the present study.
We also thank Dr. Y. Yasuda, M. Muramoto, and N. Katayama for
assistance during the experiment and J. Fox for reviewing the English
in the manuscript.
| |
FOOTNOTES |
This research was supported in part by the Ono Sports Science
Foundation and by a Grant-in-Aid for Science Research from the Japanese
Ministry of Education, Science and Culture (Grant no. 12480009).
Address for reprint requests and other correspondence: K. Katayama, Research Center of Health, Physical Fitness and Sports, Nagoya Univ., Nagoya 464-8601, Japan.
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 5 October 2000; accepted in final form 2 November 2000.
| |
REFERENCES |
1.
Alexander, JK,
Hartley LH,
Modelski M,
and
Grover RF.
Reduction of stroke volume during exercise in man following ascent to 3,100 m altitude.
J Appl Physiol
23:
849-858,
1967[Free Full Text].
2.
Aoyagi, T.
Pulse oximetry.
Kokyu
11:
560-567,
1992.
3.
Bebout, DE,
Story D,
Roca J,
Gonzalez A,
Haab P,
Hogan MC,
Ueno O,
and
Wagner PD.
Effects of altitude acclimatization on the alveolar-arterial PO2 difference (A-aPO2) in man (Abstract).
FASEB J
2:
8272,
1988.
4.
Bebout, DE,
Story D,
Roca J,
Hogan MC,
Poole DC,
Gonzalez-Camarena R,
Ueno O,
Haab P,
and
Wagner PD.
Effects of altitude acclimatization on pulmonary gas exchange during exercise.
J Appl Physiol
67:
2286-2295,
1989[Abstract/Free Full Text].
5.
Beidleman, BA,
Muza SR,
Rock PB,
Fulco CS,
Lyons TP,
Hoyt RW,
and
Cymerman A.
Exercise responses after altitude acclimatization are retained during reintroduction to altitude.
Med Sci Sports Exerc
29:
1588-1595,
1997[ISI][Medline].
6.
Bender, PR,
Groves BM,
McCullough RE,
McCullough RG,
Trad L,
Young AJ,
Cymerman A,
and
Reeves JT.
Decreased exercise muscle lactate release after high altitude acclimatization.
J Appl Physiol
67:
1456-1462,
1989[Abstract/Free Full Text].
7.
Bender, PR,
McCullough RE,
McCullough RG,
Huang SY,
Wagner PD,
Cymerman A,
Hamilton AJ,
and
Reeves JT.
Increased exercise SaO2 independent of ventilatory acclimatization at 4,300 m.
J Appl Physiol
66:
2733-2738,
1989[Abstract/Free Full Text].
8.
Benoit, H,
Busso T,
Castells J,
Denis C,
and
Geyssant A.
Influence of hypoxic ventilatory response on arterial O2 saturation during maximal exercise in acute hypoxia.
Eur J Appl Physiol
72:
101-105,
1995.
9.
Benoit, H,
Germain M,
Barthélémy JC,
Denis C,
Castells J,
Dormois D,
Lacour JR,
and
Geyssant A.
Pre-acclimatization to high altitude using exercise with normobaric hypoxic gas mixtures.
Int J Sports Med
13, Suppl 1:
S213-S216,
1992.
10.
Chua, TP,
and
Coats AJS
The reproducibility and comparability of tests of the peripheral chemoreflex: comparing the transient hypoxic ventilatory drive test and the single-breath carbon dioxide response test in healthy subjects.
Eur J Clin Invest
25:
887-892,
1995[ISI][Medline].
11.
Fatemian, M,
and
Robbins PA.
Human ventilatory response to CO2 after 8 h of isocapnic or poikilocapnic hypoxia.
J Appl Physiol
85:
1922-1928,
1998[Abstract/Free Full Text].
12.
Forster, HV,
Dempsey JA,
Birnbaum ML,
Reddan WG,
Thoden J,
Grover RF,
and
Rankin J.
Effect of chronic exposure to hypoxia on ventilatory response to CO2 and hypoxia.
J Appl Physiol
31:
586-592,
1971[Free Full Text].
13.
Gabel, RA,
Kronenberg RS,
and
Severinghaus JW.
Vital capacity breaths of 5% or 15% CO2 in N2 or O2 to test carotid chemosensitivity.
Respir Physiol
17:
195-208,
1973[ISI][Medline].
14.
Gozal, D,
Arens R,
Omlin KJ,
Marcus CL,
and
Keens TG.
Maturational differences in step vs. ramp hypoxic and hypercapnic ventilatory responses.
J Appl Physiol
76:
1968-1975,
1994[Abstract/Free Full Text].
15.
Hackett, PH,
and
Oelz O.
The Lake Louise Consensus on the definition and quantification of altitude illness.
In: Hypoxia and Mountain Medicine, edited by Sutton JR,
Coates G,
and Houston CS.. Burlington, VT: Queen City Printers, 1992, p. 327-330.
16.
Harms, CA,
and
Stager JM.
Low chemoresponsiveness and inadequate hyperventilation contribute to exercise-induced hypoxemia.
J Appl Physiol
79:
575-580,
1995[Abstract/Free Full Text].
17.
Horstman, D,
Weiskopf R,
and
Jackson RE.
Work capacity during 3-wk sojourn at 4,300 m: effects of relative polycythemia.
J Appl Physiol
49:
311-318,
1980[Free Full Text].
18.
Huang, SY,
Alexander JK,
Grover RF,
Maher JT,
McCullough RE,
McCullough RG,
Moore LG,
Sampson JB,
Weil JV,
and
Reeves JT.
Hypocapnia and sustained hypoxia blunt ventilation on arrival at high altitude.
J Appl Physiol
56:
602-606,
1984[Abstract/Free Full Text].
19.
Katayama, K,
Sato Y,
Ishida K,
Mori S,
and
Miyamura M.
The effects of intermittent exposure to hypoxia during endurance exercise training on the ventilatory responses to hypoxia and hypercapnia in humans.
Eur J Appl Physiol
78:
189-194,
1998.
20.
Katayama, K,
Sato Y,
Morotome Y,
Shima N,
Ishida K,
Mori S,
and
Miyamura M.
Ventilatory chemosensitive adaptations to intermittent hypoxic exposure with endurance training and detraining.
J Appl Physiol
86:
1805-1811,
1999[Abstract/Free Full Text].
21.
Katayama, K,
Sato Y,
Morotome Y,
Shima N,
Ishida K,
Mori S,
and
Miyamura M.
Cardiovascular response to hypoxia after endurance training at altitude and sea level and after detraining.
J Appl Physiol
88:
1221-1227,
2000[Abstract/Free Full Text].
22.
Khoo, MCK
A model-based evaluation of the single-breath CO2 ventilatory response test.
J Appl Physiol
68:
393-399,
1990[Abstract/Free Full Text].
23.
King, AB,
and
Robinson SM.
Ventilation response to hypoxia and acute mountain sickness.
Aerospace Med
43:
419-421,
1972[Medline].
24.
Kronenberg, R,
Hamilton FN,
Gabel R,
Hickey R,
Read DJC,
and
Severinghaus J.
Comparison of three methods for quantitating respiratory response to hypoxia in man.
Respir Physiol
16:
109-125,
1972[ISI][Medline].
25.
Lefrancois, R,
Gautier H,
Pasquis P,
Cevaer AM,
Hellot MF,
and
Leroy J.
Chemoreflex ventilatory response to CO2 in man at low and high altitudes.
Respir Physiol
14:
296-306,
1972[ISI][Medline].
26.
Lenfant, C,
Torrance JD,
and
Reynafarje C.
Shift of the O2-Hb dissociation curve at altitude: mechanism and effect.
J Appl Physiol
30:
625-631,
1971[Free Full Text].
27.
Levine, BD,
Friedman DB,
Engfred K,
Hanel B,
Kjaer M,
Clifford PS,
and
Secher NH.
The effect of normoxic or hypobaric hypoxic endurance training on the hypoxic ventilatory response.
Med Sci Sports Exerc
24:
769-775,
1992[ISI][Medline].
28.
Martin, BJ,
Sparks KE,
Zwillich CW,
and
Weil JV.
Low exercise ventilation in endurance athletes.
Med Sci Sports
11:
181-185,
1979[ISI][Medline].
29.
Martin, BJ,
Weil JV,
Sparks KE,
McCullough RE,
and
Grover RF.
Exercise ventilation correlates positively with ventilatory chemoresponsiveness.
J Appl Physiol
45:
557-564,
1978[Abstract/Free Full Text].
30.
Masuyama, S,
Kimura H,
Sugita T,
Kuriyama T,
Tatsumi K,
Kunitomo F,
Okita S,
Tojima H,
Yuguchi Y,
Watanabe S,
and
Honda Y.
Control of ventilation in extreme-altitude climbers.
J Appl Physiol
61:
500-506,
1986[Abstract/Free Full Text].
31.
McClean, PA,
Phillipson EA,
Martinez D,
and
Zamel N.
Single breath of CO2 as a clinical test of the peripheral chemoreflex.
J Appl Physiol
64:
84-89,
1988[Abstract/Free Full Text].
32.
Moore, LG,
Cymerman A,
Shao-Yung H,
McCullough RE,
McCullough RG,
Rock PB,
Young A,
Young PM,
Bloedow D,
Weil JV,
and
Reeves JT.
Propranolol does not impair exercise oxygen uptake in normal men at high altitude.
J Appl Physiol
61:
1935-1941,
1986
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ABSTRACT
INTRODUCTION
