| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
University Laboratory of Physiology, University of Oxford, Oxford OX1 3PT, United Kingdom
 |
ABSTRACT |
|---|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
During
ventilatory acclimatization to hypoxia (VAH), the relationship between
ventilation (
E) and end-tidal
PCO2 (PETCO2) changes.
This study was designed to determine 1) whether these changes can be seen
early in VAH and 2) if these changes
are present, whether the responses differ between isocapnic and
poikilocapnic exposures. Ten healthy volunteers were studied by using
three 8-h exposures: 1) isocapnic
hypoxia (IH), end-tidal PO2
(PETO2) = 55 Torr and
PETCO2 held at the
subject's normal prehypoxic value;
2) poikilocapnic hypoxia (PH),
PETO2 = 55 Torr; and
3) control (C), air breathing. The
E-PETCO2
relationship was determined in hyperoxia (PETO2 = 200 Torr) before
and after the exposures. We found a significant increase in the
slopes of
E-PETCO2 relationship after both hypoxic exposures compared with control (IH vs.
C, P < 0.01; PH vs. C,
P < 0.001; analysis of covariance with pairwise comparisons). This increase was not significantly different between protocols IH and
PH. No significant changes in the
intercept were detected. We conclude that 8 h of hypoxia, whether
isocapnic or poikilocapnic, increases the sensitivity of the hyperoxic
chemoreflex response to CO2.
hypercapnic sensitivity; ventilatory acclimatization; altitude
| |
INTRODUCTION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
VENTILATORY ACCLIMATIZATION to hypoxia (VAH) in humans
is characterized by a progressive increase in ventilation
(E) and reduction in end-tidal
PCO2
(PETCO2), which begins within hours of exposure to hypoxia and continues to develop over a number of days. The underlying changes in respiratory control include a change in slope and intercept for the relationship
between E and
PETCO2 (3, 8, 14, 15, 17)
and an increase in the ventilatory sensitivity to hypoxia (8, 9, 17,
20).
One question that arises is whether these changes in the respiratory
control system are driven directly by the hypoxic exposure or whether
they are brought about indirectly by the respiratory alkalosis that
normally accompanies VAH. In the case of the increase in ventilatory
sensitivity to hypoxia, it has now been shown in humans that the early
changes in VAH (first 8 h of hypoxia) arise directly from the
exposure to hypoxia (11, 12). In the case of the changes in
intercept and slope for the relationship between E and
PETCO2, the evidence is much
less clear. On one hand, evidence obtained in goats suggests that, for
hyperventilation to persist on return to euoxia after VAH, a prolonged
systemic (central nervous system) hypocapnic alkalosis is required (7). On the other hand, in humans, Tansley et al. (18) reported that an 8-h
exposure to hypoxia resulted in a persistent subsequent hyperventilation under hyperoxic conditions (at a fixed
PETCO2) and that this effect
did not differ between hypoxic exposures carried out under isocapnic
and poikilocapnic conditions. A result apparently somewhere between
these two was obtained by Eger et al. (6), who found that, after an 8-h
period of hypocapnia in humans, there was a leftward shift in the
PETCO2 associated with a
E of 15 l · min
1 · m2
under mild hyperoxic conditions but that this leftward shift was
greater if the hypocapnic exposure was also associated with exposure to
hypoxia. A similar effect on spontaneous
PETCO2 under mildly
hyperoxic conditions has been reported after a comparison of 26 h of
hypocapnic ventilation with and without hypoxia (5). None of these
studies in humans produces unequivocal evidence as to whether it is the
slope or the intercept (or both) of the relationship between
E and
PETCO2 in hyperoxia that is affected.
The present study was designed to look at the effects of 8-h exposures
of hypoxia on the slope and intercept of the relationship between
E and
PETCO2. As in the case of
the study by Tansley et al. (18), isocapnic and poikilocapnic exposures
were compared to determine whether the respiratory alkalosis normally associated with hypoxia at altitude has an effect on the responses observed.
| |
METHODS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Subjects. Ten healthy volunteers (7 men, 3 women), aged between 18 and 24 yr, took part in the study. The experiment was fully explained in written and verbal forms to all participants. Informed consent was obtained from each subject before each experiment. The study was approved by the Central Oxford Research Ethics Committee.
Protocols. Each subject visited the laboratory at least twice before any of the main experiments was undertaken. In these short visits, the subject was introduced to and familiarized with the apparatus and some initial measurements of control PETCO2 were obtained. Before each of the main experiments, the subjects were told to make sure that they had a good night's rest and that they did not exert themselves excessively when coming to the laboratory. No measurements were taken for 10-15 min after the subject's arrival in the laboratory.
The main experiments were carried out in random order on three separate days at least 1 wk apart. Female subjects were always studied at the same phase of their menstrual cycle. The three 8-h exposures used for each subject were 1) isocapnic hypoxia (IH), 2) poikilocapnic hypoxia (PH), and 3) control (C). For protocol IH, end-tidal PO2 (PETO2) was held at 55 Torr and PETCO2 was held at the subject's normal (prehypoxic) value. For protocol PH, PETO2 was held at 55 Torr and PETCO2 was not controlled. For protocol C, the subject was exposed to air as inspired gas. In each of these protocols, the subjects were given a light lunch at ~1:00 PM. If the subjects needed to urinate, they were free to leave the chamber briefly for that purpose. Otherwise, they remained in the chamber for the full 8 h. Values for air-breathing PETCO2 were determined before and 0.5 h after each 8-h exposure. After these measurements were made, the ventilatory response to hypercapnia was determined in a protocol lasting 20 min. In this protocol, PETO2 was held at 200 Torr throughout and PETCO2 was increased by 3 Torr every 5 min, starting at 1-2 Torr above the control value determined before the start of the chamber exposure. Therefore, the four levels of PETCO2 desired were ~1.5, ~4.5, ~7.5, and ~10.5 Torr above the control PETCO2.Technique. The 8-h exposures were conducted with individual subjects inside a purpose-built chamber with ample room to sit or move around comfortably. Within the chamber the composition of gas can be altered, which obviates the need for subjects to breathe via a face mask or mouthpiece. Fine nasal catheters were held at the opening of each of the subject's nostrils by a nasal oxygen-therapy mask. The respired gas was sampled (80 ml/min) via these catheters and analyzed for PO2 and PCO2 by a mass spectrometer. The subject also wore a pulse oximeter on a finger to monitor arterial O2 saturation. The values for PO2, PCO2, and O2 saturation were sampled by a computer every 20 ms. The computer program identified the ends of inspiration and expiration from the PCO2 profile and recorded the inspired and end-tidal values for PO2 and PCO2 together with O2 saturation at the end of each breath. Before the subject entered the chamber, the composition of the inspired gas necessary to produce the desired end-tidal partial pressures was estimated and set manually. During the experiment the composition of the inspired gas was altered by the computer every 5 min to maintain the end-tidal partial pressures at the desired level. Manual alteration at other intervals was also possible. This system has been described in greater detail elsewhere (10).
Ventilatory responses to hypercapnia were measured outside the chamber. The subject was seated in an upright position and breathed through a mouthpiece, with his or her nose occluded by a clip. A turbine volume-measuring device fixed in series with the mouthpiece measured the respiratory volumes; a pneumotachograph was used to record flows and timing information. The total dead space associated with the apparatus was 100 ml. Gas was sampled (20 ml/min) from this dead space, close to the mouth, and analyzed by mass spectrometry for PO2 and PCO2. A pulse oximeter was attached to a forefinger to monitor the O2 saturation of the blood. All the data were sampled by a data-acquisition computer every 20 ms, and PETCO2, PETO2, inspiratory and expiratory volumes, and durations for each breath were recorded. To obtain accurate control over PETCO2 and PETO2 during the measurements of hypercapnic sensitivity, an end-tidal forcing system was employed. Before the experiment, a "forcing function" containing the predicted inspired gas values required to achieve the desired PETO2 and PETCO2 was entered into a second (controlling) computer. During the experiment, actual values of PETO2 and PETCO2 were passed breath by breath to the controlling computer from the data-acquisition computer. The actual end-tidal values were compared with the desired values, and a new inspired gas mixture was calculated by using an integral-proportional feedback scheme. The controlling computer generated the new inspired gas mixture by using a fast gas-mixing system that was controlled from the program. This system has been described in more detail elsewhere (13, 16).Data analysis.
Average values for E and
PETCO2 were calculated for
the last minute at each level of hypercapnia. The
E-PETCO2 response line was obtained by fitting a straight line to each set of
four data points by using simple linear regression. Values for the
slope and intercept (PETCO2
at E = 0) were obtained from this
procedure. Mean changes within each protocol (PM 
AM) were
assessed statistically by using paired
t-tests. Comparisons between protocols
were undertaken by using analysis of covariance. In the case of the
E-PETCO2
response curves, this analysis was undertaken on the log of values
to help stabilize variance and provide more normal distributions (1). A
value of P < 0.05 was used for
statistical significance, except for subsequent pairwise comparisons
among the three protocols in which P < 0.017 was used to allow for multiple (3) comparisons. The SPSS
statistical package was used for these analyses.
| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Subjects. All subjects completed the series of experiments and provided data that were suitable for analysis. During the 8-h exposures, subjects were generally comfortable and spent their time reading, watching television, or playing computer games. Some subjects reported mild headaches toward the end of some of the exposures; one subject found the level of ventilation rather uncomfortable during the last hour of isocapnic hypoxia, and another felt slightly dizzy toward the end of the poikilocapnic exposure. Control values for PETCO2 for each subject for each protocol are given in Table 1.
|
End-tidal gas values in the chamber. Figure 1 shows the end-tidal gases recorded while the subjects were in the chamber, averaged every 5 min, for each of the 10 subjects and for all 3 protocols. The initial and final values for each subject and protocol are given in Table 1. The plots illustrate the quality of the control that was achieved over PETCO2 and PETO2 in protocol IH and over PETO2 in protocol PH. Average values for saturation obtained from the pulse oximeter at the beginning and end of the chamber exposure were 92.8 ± 2.6 and 89.4 ± 1.4% for protocol IH, 92.5 ± 1.5 and 89.8 ± 0.9% for protocol PH, and 97.8 ± 0.7 and 97.8 ± 0.8% for protocol C, respectively.
|
0.4 to 3.5 Torr, P = NS]. To provide
comparison among the protocols, an analysis of covariance was
performed on the values for
PETCO2 for the last 5 min in
the chamber (Table 1) with the values for the first 5 min in the
chamber as a covariate, together with subjects as a random factor and
protocols as a fixed factor. This revealed that the protocols differed
(P < 0.01) with respect to
the change in PETCO2, and
pairwise comparisons showed significant differences between
protocol PH and the other two
protocols but not between protocol IH
and protocol C.
PETCO2 under
air-breathing conditions.
Values for airbreathing
PETCO2 0.5 h after the end
of the chamber exposure along with the control values are given in
Table 1. PETCO2 fell after
protocol IH by 2.1 Torr (95% CI 1.0 to 3.2 Torr, P < 0.005); after
protocol PH
PETCO2 fell by 1.8 Torr
(95% CI 0.5 to 3.0 Torr, P < 0.05)
but was unaltered after protocol C
(rise of 0.1 Torr, 95% CI 0.9 to 1.2 Torr,
P = NS). A comparison among the
protocols was provided statistically by using the control values as a
covariate, together with subjects as a random factor and protocols as a
fixed factor. There was a significant effect of protocol
(P < 0.001) on
PETCO2, and pairwise
comparisons revealed significant differences between protocol C and the other two
protocols, but not between protocols PH and IH.
Ventilatory response to hypercapnia.
Figure 2 illustrates the
E-PETCO2
responses obtained for each of the 10 subjects before and after the 8-h
exposure associated with each protocol. The data points represent
averages over the last minute of each level of
PETCO2. It can be seen that
the values for PETCO2 are
generally well matched before and after the hypoxic exposure and among
protocols.
|
1 · Torr1
(95% CI 0.3 to 1.3 l · min1 · Torr1,
P < 0.005) and after
protocol PH it was 1.2 l · min1 · Torr1
(95% CI 0.3 to 2.0 l · min1 · Torr1,
P < 0.05). The mean slope was
unaltered in protocol C (increase of
0.0 l · min1 · Torr1,
95% CI 0.2 to 0.3 l · min1 · Torr1,
P = NS). To compare protocols, an
analysis of covariance was performed on the logs of the slopes after
the chamber exposure, with the logs of the slopes preceding the chamber
exposure as a covariate, the subjects as a random factor, and protocol
as a fixed factor. This revealed significant differences among the protocols (P < 0.001).
Subsequent pairwise comparisons showed that both hypoxic exposures were
significantly different from control (protocol
IH vs. protocol C,
P < 0.01; protocol
PH vs. protocol C,
P < 0.001), but there was no
significant difference between the two hypoxic protocols.
|
E = 0) in any protocol. This was
confirmed statistically (decreases in intercept were the following:
protocol IH, 0.5 Torr, 95% CI
0.6 to 1.6 Torr, P = NS;
protocol PH, 0.0 Torr, 95% CI
1.7 to 1.6 Torr, P = NS;
protocol C, 0.1 Torr, 95% CI
1.1 to 1.4, P = NS).
Analysis of covariance on the value of the intercept after the chamber
exposure, with the value of the intercept before the chamber exposure
as a covariate, the subjects as a random factor, and protocol as a
fixed factor, confirmed there were no differences among protocols
(P = 0.46, NS).
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
The main findings from this study are
1) 8 h of hypoxic exposure results
in an increase in the slope of the relationship between E and
PETCO2 in hyperoxia but does
not affect the intercept of this relationship with the
PETCO2 axis; and
2) this increase in slope over the 8 h of hypoxic exposure does not differ significantly between isocapnic
and poikilocapnic hypoxia, although the degree of hypocapnia induced
was quite limited in this study. The second finding suggests that the
increase in CO2 sensitivity in
poikilocapnic hypoxia is due to hypoxia per se rather than to the
concomitant hypocapnia. The results also suggest that, whereas the
increase in slope of the
E-PETCO2
relationship may begin early in the process of acclimatization to
altitude, this is not the case for the shift in intercept. Thus the
increase in slope of the
E-PETCO2
relationship and the shift in intercept that occur during
acclimatization are likely to arise, at least in part, from different mechanisms.
Air breathing and chamber values for
PETCO2.
The results for air-breathing
PETCO2 before and after the
chamber exposure demonstrate that a fall in
PETCO2 occurs after
sustained hypoxia that is not dependent on an associated hypocapnic
alkalosis during the hypoxic period. This result is consistent with the
previous observation (18) that hyperoxic E at constant
PETCO2 is increased after 8 h of both isocapnic and poikilocapnic hypoxia.
Comparison with other studies.
Eger et al. (6) studied four subjects over 8-h periods at different
levels of PETCO2 (hypocapnia
was achieved by hyperventilation) with and without concomitant hypoxia.
They found that the ratio of the hyperoxic
E-PETCO2
response slope (PM/AM) was increased after the hypoxic exposures but
not after the euoxic exposures, although the significance of their result was uncertain because the control values for the
E-PETCO2 response slope differed significantly between the hypoxic and euoxic
protocols. Our results remove this uncertainty because the control
slopes did not differ among the three protocols of our study (ANOVA,
NS, P = 0.73).
E-PETCO2
response and that "Hypoxia was associated with a greater shift of
the CO2-response curve than
normoxia for a given change in acclimatization
PACO2." At first sight,
these results may appear somewhat contradictory to our finding that
there was no shift in the
E-PETCO2 response, especially in the case of protocol
PH. However, there are two important differences
between the results of Eger et al. and those of the present study.
First, Eger et al. employed much greater degrees of hypocapnia,
generated by forced hyperventilation, whereas our levels of
hypocapnia were much more modest and resulted solely from the
hypoxic stimulus. Second, Eger et al. define shift in relation to
an arbitrarily chosen level of ventilation at 15 l · min1 · m2,
whereas our study defines shift in relation to the intercept of the
E-PETCO2
relationship with the
PETCO2 axis.
To compare the results of Eger et al. (6) with those of the present
study in a more direct fashion, we recalculated the intercepts of Eger
et al. to correspond with those of the present study
(PETCO2 at
E = 0) and subjected the results to an
analysis of variance with subjects as a random factor, the presence or
absence of hypoxia in the 8-h period as a fixed factor, and the degree
of hypocapnia in the 8-h period as a covariate. The results showed that
the degree of hypocapnia significantly affected the shift in the
intercept but that hypoxia itself had no significant independent
effect, in keeping with the results of our study. The interactive term
between hypoxia and hypocapnia, which indicates the influence of
hypoxia on the shift associated with a given level of hypocapnia,
approached significance (P = 0.064)
but did not quite reach it.
Cruz et al. (4) compared the effects of 100 h of poikilocapnic hypoxia
in one group of four subjects with 100 h of hypoxia with supplemental
CO2 in another group of four
subjects. They were unable to detect a significant increase in the
slope of the E-PETCO2
relationship over time, although the figure in their paper illustrates
a trend in this direction. Similarly, they were unable to detect a
change in the intercept of this relationship until 75 h into the
experiment, a result in keeping with our study. At 75 h, a reduction in
intercept was detected for the poikilocapnic hypoxic exposure but not
for the hypoxic exposure with added
CO2.
Mechanisms and animal models.
Engwall and Bisgard (7) have reported that, in goats, both isocapnic
and poikilocapnic exposures to hypoxia altered the subsequent
hyperoxic
E-PETCO2
relationship. By way of contrast, Weizhen et al. (19) have reported
that, if the conditioning period of hypoxia were restricted so that
it affected the central nervous system but not the carotid bodies, then
no changes in the euoxic
E-PETCO2
relationship occurred. These results suggest that it may be the
presence of hypoxia at the carotid body that is important for altering
the
E-PETCO2 response relationship. Neither of these two studies nor the present study has identified unambiguously whether this alteration in overall
CO2 response arises from a change
in the peripheral or the central chemoreflex response to
CO2. On one hand, if hypoxia is
exerting its modulatory effects on the
CO2 response at the carotid body,
then it might seem more likely that the alteration would be in the
peripheral chemoreflex response to
CO2. On the other hand, the
responses to CO2 were measured
under conditions of either euoxia (19) or hyperoxia (present study and
Ref. 7), where the peripheral chemoreflex contribution is generally
considered to have been minimized, and this might suggest that the
change is an alteration in the central chemoreflex response to
CO2.
E-PETCO2
response relationship with the
PETCO2 axis. One possibility
is that these differences with the present study are simply reflecting
the difference in physiology between goats and humans. Goats are
reported to acclimatize much more quickly than do humans (2), and this
may explain why a leftward shift in
PETCO2 intercept has
appeared after 4 h of poikilocapnic hypoxia at 40 Torr in goats but
not after 8 h of hypoxia at 55 Torr in humans. The absence of change in
CO2 sensitivity after
poikilocapnic hypoxia is more difficult to explain, especially as a
change in sensitivity was observed after their isocapnic exposures. One
possibility is their result is a type II statistical error. On the
basis of the SEs reported for their study, an unpaired calculation of
the 95% CI for the change in slope after poikilocapnic hypoxia
suggests that there would have to have been an ~40% increase in
CO2 sensitivity for the increase
to have been significant. Although this percentage should be lower with
a paired calculation, the measured increase in
CO2 sensitivity after isocapnic
hypoxia of 32% certainly indicates that a type II error could have occurred.
| |
ACKNOWLEDGEMENTS |
|---|
We thank David O'Connor for skilled technical assistance and the subjects for their cheerful cooperation.
| |
FOOTNOTES |
|---|
This study was funded by the Wellcome Trust.
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: P. A. Robbins, Univ. Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK (E-mail: peter.robbins{at}physiol.ox.ac.uk).
Received 22 January 1998; accepted in final form 23 July 1998.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
1.
Armitage, P.,
and
G. Berry.
Statistical Methods in Medical Research (2nd ed.). Oxford, UK: Blackwell Scientific, 1987.
2.
Bisgard, G. E.,
and
H. V. Forster.
Ventilatory responses to acute and chronic hypoxia.
In: Handbook of Physiology. Environmental Physiology. Bethesda, MD: Oxford Univ. Press, 1996, sect. 4, vol. II, chapt. 52, p. 1207-1239.
3.
Chiodi, H.
Respiratory adaptations to chronic high-altitude hypoxia.
J. Appl. Physiol.
10:
81-87,
1957
4.
Cruz, J. C.,
J. T. Reeves,
R. F. Grover,
J. T. Maher,
R. E. McCullough,
A. Cymerman,
and
J. C. Denniston.
Ventilatory acclimatization to high altitude is prevented by CO2 breathing.
Respiration
39:
121-130,
1980[Medline].
5.
Dempsey, J. A.,
H. V. Forster,
N. Gledhill,
and
G. A. doPico.
Effects of moderate hypoxemia and hypocapnia on CSF [H+] and ventilation in man.
J. Appl. Physiol.
38:
665-674,
1975
6.
Eger, E. I. I.,
R. H. Kellogg,
A. H. Mines,
M. Lima-Ostos,
C. G. Morrill,
and
D. W. Kent.
Influence of CO2 on ventilatory acclimatization to altitude.
J. Appl. Physiol.
24:
607-615,
1968
7.
Engwall, M. J. A.,
and
G. E. Bisgard.
Ventilatory responses to chemoreceptor stimulation after hypoxic acclimatization in awake goats.
J. Appl. Physiol.
69:
1236-1243,
1990
8.
Forster, H. V.,
J. A. Dempsey,
M. L. Birnbaum,
W. G. Reddan,
J. Thoden,
R. F. Grover,
and
J. Rankin.
Effect of chronic exposure to hypoxia on ventilatory response to CO2 and hypoxia.
J. Appl. Physiol.
31:
586-592,
1971
9.
Goldberg, S. V.,
R. B. Schoene,
D. Haynor,
B. Trimble,
E. R. Swenson,
J. B. Morrison,
and
E. J. Banister.
Brain tissue pH and ventilatory acclimatization to high altitude.
J. Appl. Physiol.
72:
58-63,
1992
10.
Howard, L. S. G. E.,
R. A. Barson,
B. P. A. Howse,
T. R. McGill,
M. E. McIntyre,
D. F. O'Connor,
and
P. A. Robbins.
A chamber for controlling the end-tidal gas tensions over sustained periods in humans.
J. Appl. Physiol.
78:
1088-1091,
1995
11.
Howard, L. S. G. E.,
and
P. A. Robbins.
Alterations in respiratory control during 8 h of isocapnic and poikilocapnic hypoxia in humans.
J. Appl. Physiol.
78:
1098-1107,
1995
12.
Howard, L. S. G. E.,
and
P. A. Robbins.
Ventilatory response to 8 h of isocapnic and poikilocapnic hypoxia in humans.
J. Appl. Physiol.
78:
1092-1097,
1995
13.
Howson, M. G.,
S. Khamnei,
M. E. McIntyre,
D. F. O'Connor,
and
P. A. Robbins.
A rapid computer-controlled binary gas-mixing system for studies in respiratory control (Abstract).
J. Physiol. (Lond.)
394:
7P,
1987.
14.
Michel, C. C.,
and
J. S. Milledge.
Respiratory regulation in man during acclimatisation to high altitude.
J. Physiol. (Lond.)
168:
631-643,
1963.
15.
Rahn, H.,
R. C. Stroud,
S. M. Tenney,
and
J. C. Mithoefer.
Adaptation to high altitude: respiratory response to CO2 and O2.
J. Appl. Physiol.
6:
158-162,
1953
16.
Robbins, P. A.,
G. D. Swanson,
and
M. G. Howson.
A prediction-correction scheme for forcing alveolar gases along certain time courses.
J. Appl. Physiol.
52:
1353-1357,
1982
17.
Sato, M.,
J. W. Severinghaus,
F. L. Powell,
F.-D. Xu,
and
M. J. Spellman, Jr.
Augmented hypoxic ventilatory response in men at altitude.
J. Appl. Physiol.
73:
101-107,
1992
18.
Tansley, J. G.,
C. Clar,
M. E. F. Pedersen,
and
P. A. Robbins.
Human ventilatory response to acute hyperoxia during and after 8 h of both isocapnic and poikilocapnic hypoxia.
J. Appl. Physiol.
82:
513-519,
1997
19.
Weizhen, N.,
M. J. A. Engwall,
L. Daristotle,
J. Pizarro,
and
G. E. Bisgard.
Ventilatory effects of prolonged systemic (CNS) hypoxia in awake goats.
Respir. Physiol.
87:
37-48,
1992[Medline].
20.
White, D. P.,
K. Gleeson,
C. K. Pickett,
A. M. Rannels,
A. Cymerman,
and
J. V. Weil.
Altitude acclimatization: influence on periodic breathing and chemoresponsiveness during sleep.
J. Appl. Physiol.
63:
401-412,
1987
This article has been cited by other articles:
|
|
 |
|
  G. R. Scott and W. K. Milsom Control of breathing and adaptation to high altitude in the bar-headed goose Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R379 - R391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Liu, T. G. Smith, G. M. Balanos, J. Brooks, A. Crosby, M. Herigstad, K. L. Dorrington, and P. A. Robbins Lack of involvement of the autonomic nervous system in early ventilatory and pulmonary vascular acclimatization to hypoxia in humans J. Physiol., February 15, 2007; 579(1): 215 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Crosby, N. P. Talbot, G. M. Balanos, S. Donoghue, M. Fatemian, and P. A. Robbins Respiratory effects in humans of a 5-day elevation of end-tidal PCO2 by 8 Torr J Appl Physiol, November 1, 2003; 95(5): 1947 - 1954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Katayama, Y. Sato, Y. Morotome, N. Shima, K. Ishida, S. Mori, and M. Miyamura Intermittent hypoxia increases ventilation and SaO2 during hypoxic exercise and hypoxic chemosensitivity J Appl Physiol, April 1, 2001; 90(4): 1431 - 1440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fatemian and P. A. Robbins Physiological and Genomic Consequences of Intermittent Hypoxia: Selected Contribution: Chemoreflex responses to CO2 before and after an 8-h exposure to hypoxia in humans J Appl Physiol, April 1, 2001; 90(4): 1607 - 1614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Ren, M. Fatemian, and P. A. Robbins Changes in respiratory control in humans induced by 8 h of hyperoxia J Appl Physiol, August 1, 2000; 89(2): 655 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Clar, K. L. Dorrington, and P. A. Robbins Ventilatory effects of 8 h of isocapnic hypoxia with and without beta -blockade in humans J Appl Physiol, June 1, 1999; 86(6): 1897 - 1904. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
PETCO2;
top row),
PETCO2
(middle row), and end-tidal
PO2
(PETO2;
bottom row) averaged every 5 min
from data collected breath by breath over 8 h for all 10 subjects
during isocapnic hypoxia protocol (left
column), poikilocapnic hypoxia protocol
(middle
column), and control protocol
(right column).
) and
after (
) chamber exposure. Data were recorded breath by breath
during hypercapnic sensitivity test and averaged over last minute for
each level of PETCO2. No. on
panel, subject no.