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University Laboratory of Physiology, University of Oxford, Oxford OX1 3PT, United Kingdom
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Ventilatory acclimatization to
hypoxia is associated with an increase in ventilation under conditions
of acute hyperoxia
(
Ehyperoxia) and an increase in acute hypoxic ventilatory response (AHVR). This
study compares 48-h exposures to isocapnic hypoxia
( protocol I) with 48-h
exposures to poikilocapnic hypoxia ( protocol
P) in 10 subjects to assess the importance of
hypocapnic alkalosis in generating the changes observed in ventilatory
acclimatization to hypoxia. During both hypoxic exposures,
end-tidal PO2 was maintained at
60 Torr, with end-tidal PCO2 held at the subject's prehypoxic level
( protocol I) or uncontrolled
( protocol P).
Ehyperoxia
and AHVR were assessed regularly throughout the exposures.
Ehyperoxia
(P < 0.001, ANOVA) and AHVR
(P < 0.001) increased during the
hypoxic exposures, with no significant differences between
protocols I and
P. The increase in
Ehyperoxia
was associated with an increase in slope of the
ventilation-end-tidal PCO2 response
(P < 0.001) with no significant
change in intercept. These results suggest that changes in respiratory
control early in ventilatory acclimatization to hypoxia
result from the effects of hypoxia per se and not the alkalosis
normally accompanying hypoxia.
ventilation; acclimatization; alkalosis
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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IN HUMANS, VENTILATORY acclimatization to hypoxia (VAH)
is a progressive increase in ventilation
(E) over
hours/days accompanied by a progressive decrease in the end-tidal
PCO2
(PETCO2). There appear to be
at least two processes contributing to this increase in ventilation:
1) a leftward shift of the
ventilatory response to an increase in
PETCO2, together with an
increase in the slope of this relationship (determined under conditions of acute euoxia/hyperoxia) (4, 12, 19, 20) and
2) an increase in acute hypoxic
ventilatory response (AHVR) (12, 13, 22, 26).
One question surrounding these processes is to what degree they develop
because of the hypoxia per se vs. to what degree they develop because
of the concomitant alkalosis. One approach to answering this question
has been to compare the effects of poikilocapnic hypoxia with those of
isocapnic hypoxia. A comparison of 8 h of poikilocapnic hypoxia with 8 h of isocapnic hypoxia has suggested that the changes in
E under acute
hyperoxic conditions
(Ehyperoxia) (24) and AHVR (15) do not depend for their development on the presence
of a respiratory alkalosis.
A criticism of these studies is that 8 h of hypoxia did not provide sufficient time for what is regarded classically as VAH in humans. Typically, the process takes several days, although substantial changes are seen by days 1 and 2. The purpose of this study was to extend the experiment comparing isocapnic and poikilocapnic hypoxia from 8 to 48 h so that the time course of the study would match more closely that normally associated with VAH in humans.
The particular questions to be addressed in this study were as follows:
1) For a 48-h conditioning period,
were there significant differences in the progressive increase in
Ehyperoxia
between isocapnic and poikilocapnic hypoxic conditioning?
2) For a 48-h period of hypoxia,
could the progressive increase in
Ehyperoxia be attributed to an increase in slope of the hyperoxic
E-PETCO2 relationship and/or a shift in the intercept of this
relationship? 3) For a 48-h
conditioning period, were there significant differences in the
progressive increase in AHVR between isocapnic and poikilocapnic hypoxic conditioning?
In addition to the study of 48 h of hypoxia, the 48-h period after the relief of hypoxia was also investigated to compare the recovery processes from the isocapnic and poikilocapnic hypoxic exposures.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Subjects. Ten healthy subjects (7 men, 3 women), 18-27 yr of age, volunteered to take part in the study. The requirements of the study were fully explained in writing and verbally in such a way that the subjects were naive as to the exact purpose of the experiment. Subjects gave informed consent before participation in the study. Each subject was required to make one or two preliminary visits to the laboratory, during which initial control measurements of PETCO2 and estimates of hypoxic sensitivity were made and subjects were familiarized with the apparatus. The research had been approved by the Central Oxford Research Ethics Committee.
Hypoxic exposure.
Two 48-h hypoxic exposures were used:
1) an isocapnic protocol
( protocol I), where end-tidal
PO2
(PETO2) was held
at 60 Torr and PETCO2 was
held at the subject's prehypoxic control value, and
2) a poikilocapnic protocol
( protocol P), where
PETO2 was held at 60 Torr
and PETCO2 was uncontrolled.
Hypoxic exposures were separated by 
1 wk and carried out in a
randomly determined order. After each hypoxic exposure the subjects
were allowed to go home but were required to return to the laboratory
at intervals over the subsequent 48 h for further testing.
E was
measured before the chamber exposures were started and then at 30 min
into the hypoxic exposure, 90 min into the hypoxic exposure, and every
2 h during wakefulness for the remainder of the 48-h protocol. Each
measurement of
E
took 5 min, and the last 2 min of this period were used to
calculate the
E for that time point. The measurements were made using inductance
plethysmography. The inductance plethysmograph was calibrated
at the end of each 5-min measurement period by asking the subject to
breathe through a mouthpiece for a further 5 min. This gave accurate
values for tidal volume using a turbine flowmeter (17) while data
collection continued with the inductance plethysmograph.
Blood samples.
Venous blood samples were taken at the times indicated in Fig.
1. The samples were taken inside the
chamber under hypoxic conditions during the hypoxic exposures and
outside the chamber with the subject breathing room air at other times.
Before each sample was taken, the hand and lower arm were warmed for 5 min using an electric heating pad in an attempt to arterialize the blood sample. A venous sample was then taken from the cubital fossa or
the dorsum of the hand. The sample was analyzed for pH, PCO2, Hb and
HCO
3 concentrations, and O2 saturation. Simultaneous
measurements of PETO2 and PETCO2 were also made,
and this end-tidal gas composition was used to estimate
arterial values for pH.
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Measurement of AHVR,
Ehyperoxia,
and the acute hypercapnic ventilatory response.
Measurements of these respiratory responses were undertaken at the
times indicated in Fig. 1. Apart from the pH-matched measurements (see
below), measurements of AHVR and
Ehyperoxia
were undertaken at all times with the
PETCO2 held at 1.5-2
Torr above the subject's initial air-breathing value before the start
of the chamber exposure (PCO2-matched measurements).
Ehyperoxia
was measured by elevating the
PETO2 to ~300 Torr for 5 min. The last 2 min of this period were used to determine
Ehyperoxia.
The acute hypercapnic ventilatory response (AHCVR) was measured at the
beginning of each day, and followed on directly from the determination
of
Ehyperoxia.
PETCO2 was elevated by 7.5 Torr above the value for the
PCO2-matched tests for 5 min.
PETO2 was kept constant at
300 Torr, the value associated with the measurement of
Ehyperoxia.
The final 2 min of data were used for calculating AHCVR along with the
results from the measurement of
Ehyperoxia.
AHVR,
Ehyperoxia,
and AHCVR were measured outside the chamber using a dynamic end-tidal
forcing system. The subject sat in an upright position and breathed
through a mouthpiece with the nose occluded with a clip. Respiratory
volumes were measured using a turbine volume-measuring device fixed in
series with the mouthpiece; flows and timing information were obtained
using a pneumotachograph. The total dead space associated with the
apparatus was 100 ml. Gas was sampled continuously from this dead space close to the mouth at a rate of 20 ml/min and analyzed by mass spectrometry for PO2 and
PCO2. The data were recorded by
computer at a sampling rate of 50 Hz; the computer was also used to
detect the ends of the expiratory and inspiratory phases from the flow
data to determine the expiratory and inspiratory duration, volumes, and
PETO2 and
PETCO2.
A forcing function containing the predicted inspired gas values
required to achieve the desired
PETO2 and
PETCO2 was entered into a
second (controlling) computer before the hyperoxic test.
During the test, actual values of
PETO2 and
PETCO2 were passed breath by
breath to this controlling computer from the data-acquisition computer.
These measured values were compared with the desired values, and a new
inspired gas mixture was calculated breath by breath using an
integral-proportional feedback scheme. The controlling computer
adjusted the inspired partial pressures of
N2,
O2, and
CO2 via a series of valves
connected to gas supplies. This system for controlling
PETCO2 and
PETO2 has been described in
greater detail elsewhere (16, 21).
Measurements of respiratory responses at matched arterial pH. If there were any significant changes in acid-base balance through renal compensation or other processes during the hypoxic exposures, then the PCO2-matched measurements above might have resulted in measurements being undertaken at different values of arterial pH. To determine whether this was of any significance, daily tests of AHVR were also carried out at a PETCO2 that should have produced the same arterial pH that occurred in the first test (0 h). The level of PETCO2 required was calculated from the pH, PCO2, Hb content, and saturation of the venous blood samples using the relationships described by Michel et al. (18). These measurements are termed "pH matched."
Modeling of hypoxic responses.
To obtain numerical estimates for AHVR from the data collected, the six
square waves of each of the AHVR tests were fit by a single-compartment
model of the peripheral chemoreflex (model 3) as described by Clement and Robbins (5). Parameter
Gp of this model reflects the
ventilatory sensitivity to hypoxia, and parameter
c reflects the
residual ventilation when no hypoxia is present. The two other
parameters of the model, which are not of such immediate interest to
this study but are provided as part of the fitting process, are the
time constant (
) and the time delay
(Td) for the
peripheral chemoreflex.
Statistical analysis. For statistical analysis the data were split into two parts: the first relates to the 48-h hypoxic period and the second to the 48 h after the relief of hypoxia. All statistical analysis was undertaken using ANOVA. In most cases a repeated-measures analysis was undertaken with protocol and time as within-subject factors. In a few cases where there appeared to be a closely linear relationship for the variable with time, a regression model was used with time as a covariate, protocol as a fixed factor, and subject as a random factor. Where time has been treated as a covariate, this is indicated.
All statistical analysis was undertaken using the SPSS software package.| |
RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Subjects.
Of the 10 subjects studied, 9 provided data that were suitable for
analysis. The remaining subject withdrew from the study during the
poikilocapnic protocol suffering from headache, nausea, and general
discomfort, which could be interpreted as symptoms of acute mountain
sickness. While in the chamber, other subjects were generally
comfortable, spending their days reading, watching television, or
playing computer games. Some did report mild headaches and, during
isocapnic hypoxia, some discomfort from the high levels of
E experienced
toward the end of the exposure. However, no others sought to withdraw
from the study. All subjects managed to sleep satisfactorily during
both protocols, although some had episodes of periodic breathing in
protocol P. During such periods the
inspired gas composition within the chamber was held constant until
regular breathing returned.
Hypoxic exposure. Figure 2 shows values for the end-tidal gas tensions and arterial O2 saturation averaged every 5 min for each of the nine subjects while in the chamber for protocols I and P. These plots illustrate the quality of control achieved over the end-tidal gases. PETO2 was maintained very close to desired values throughout the exposure for both protocols. For protocol I, PETCO2 was controlled accurately during the day but tended to rise at night when the subjects were asleep. For protocol P, PETCO2 tended to fall during the 48 h, although the diurnal variation was again evident, with higher values of PETCO2 at night. Mean values over 12-h periods for PETO2, PETCO2, and arterial O2 saturation are given in Table 1.
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E recorded in
the chamber using inductance plethysmography at 2-h intervals while the
subjects were awake. There appears to have been a progressive increase in E with time
over the 48-h hypoxic exposure during protocol I that was not apparent in protocol
P. This difference was significant (P < 0.001, time treated as a covariate).
Blood samples.
Mean values relating to blood samples are given in Table
2. There was a significant rise in Hb
concentration over the 48-h exposure to hypoxia in both protocols
(P < 0.001), with no significant difference between them. The mean value for venous saturation [53.8 ± 1.4% (SD)] indicated that the procedure of
warming the hand to obtain arterialized samples was not particularly
successful; consequently, the venous values for
PCO2 and pH were difficult to
interpret on their own. Two derived variables were calculated and are
shown in Table 2. The first, standard
HCO3 ([HCO3]std,
i.e., calculated HCO3 concentration at
40 Torr PCO2 in fully saturated
blood) showed little change in either protocol, and statistical
analysis of the values from the start of each day revealed no
significant effects of time or protocol. The second derived variable
was the calculated arterial pH, where it was assumed that
PETCO2 and
PETO2 could be used as a
measure of the PCO2 and
PO2 of arterial blood. With use of
time as a covariate, for protocol I
there was no significant change in calculated arterial pH over the 48-h
period of hypoxia, whereas for protocol
P there was a significant rise
(P < 0.005).
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Measurements of
Ehyperoxia.
An experimental determination of
Ehyperoxia
is shown in Fig. 3. Mean values for
Ehyperoxia
measured at various stages through each protocol are illustrated in
Fig. 4. There was an increase in
Ehyperoxia
over time during the hypoxic period of both protocols
(P < 0.001). This increase did not
differ significantly between the two protocols.
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Measurements of AHCVR. Ventilatory responses to hypercapnia were measured under conditions of hyperoxia every 24 h throughout the 96-h protocol (Fig. 3). Mean values for the slope and intercept of the responses are illustrated in Fig. 4. For both protocols, the slope appeared to increase during the 48 h of hypoxia and then to decrease during the subsequent 48 h of euoxia. The increase and the decrease in slope were significant (P < 0.05), with no differences being detected between the responses for protocols I and P.
Inspection of the data for the intercept of the meanE-PETCO2
responses with the x-axis for each
time period suggested that there was little change in this value over
the 48-h period of hypoxia, and indeed no significant changes were detected.
Measurements of AHVR.
Figure 3 illustrates an example of
PETO2,
PETCO2, and
E measured
breath by breath during an experimental determination of AHVR. The
PO2 record shows that the PETO2 profile followed
the required pattern accurately, with only slight
inaccuracies at the transitions between the two levels of
PETO2. The
PCO2 record shows that PETCO2 values were
maintained close to the desired level throughout the test. Average
end-tidal gas tensions and ventilatory responses for the six hypoxic
square waves averaged across all subjects are shown in Figs.
5 and 6. For
both protocols, PETCO2 appears to have been well controlled throughout. For
PETO2 the transitions
between the two levels of PO2 were
generally fairly sharp, although there was some overshoot at the relief of hypoxia.
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E suggested an
increase in the amplitude of response to the hypoxic stimulus over the 48-h period of hypoxia that was gradually reversed during the subsequent 48 h of euoxia. There also appears to have been an increase
in the baseline ventilation in euoxia. To quantify these appearances, a
dynamic model (see METHODS) was fit
to the individual responses to the hypoxic square waves to obtain
estimates for hypoxic sensitivity
(Gp) and baseline (calculated
hyperoxic) ventilation (c). As part
of this process, values for the pure delay
(Td) and associated with the acute hypoxic chemoreflex were also obtained. Mean
values for Gp and
c are summarized
for both protocols in Fig. 7. In general,
for both protocols the values for
Gp and c showed an
increase over the 48 h of hypoxia and then a decrease over the ensuing
48 h of euoxia. There was little change in [7.65 ± 5.01 (SD) s, n = 9 subjects] or
Td (4.23 ± 0.63 s).
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c
during the 48 h of hypoxia (P < 0.001), with no significant difference detected between the protocols. In the 48 h after the relief of hypoxia there was a decrease
in Gp and
c with time
(P < 0.001), again with no
differences detected between the two protocols. There were no
significant changes over time during hypoxia for
Td or , nor
were there any significant differences between
protocols I and
P for these parameters.
Table 3 gives the target
PETCO2 values for the
pH-matched tests of AHVR over the 96 h of both protocols. There appears to have been little change in this target value over time in
protocol I or
P, and this was confirmed
statistically. Thus the data from these pH-matched tests were unlikely
to yield results that were significantly different from those obtained
in the PCO2-matched tests.
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c are summarized
in Fig. 9. In general, for both protocols
the values for Gp and
c appeared to
increase over the 48 h of hypoxia and then to decrease over the ensuing 48 h of euoxia. Again, these appearances were tested
statistically. There was a significant effect of time for both
Gp and
c during the 48 h of hypoxia (P < 0.001) but no
significant difference in this process between the two protocols. There
were similar statistical observations for the 48 h after hypoxia for
Gp
(P < 0.001) and
c
(P < 0.005). ANOVA also showed no
significant changes over time during the 48 h of hypoxia for
(6.75 ± 4.79 s) or
Td (4.61 ± 0.74 s) or any significant differences between the protocols. These
results were consistent with the observations for the
PCO2-matched tests.
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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The main findings from this study were an increase in
Ehyperoxia
and an increase in AHVR over a 48-h exposure to hypoxia. This time
scale is one over which the early phases of VAH are known to occur.
Importantly, these observations did not differ significantly between
the isocapnic and poikilocapnic hypoxic exposures, which suggests that
the changes were a product of hypoxia alone and did not require the
hypocapnia and alkalosis that normally accompany VAH. These findings
were entirely consistent with previous findings from our laboratory
using 8-h exposures to hypoxia (15, 24), and the importance of the
present work is that it has extended the results into the time frame
normally associated with VAH in humans.
Control of hypoxic stimulus within the chamber. The records for PETO2 indicated that this variable was well controlled throughout the 48 h that the subjects spent in the chamber. Nevertheless, inspection of the data obtained for arterial saturation by pulse oximetry indicated that there may have been some drop in mean saturation during sleep. One possible explanation for this drop in saturation is that there was poorer ventilation-perfusion matching during sleep in the supine position under these conditions. Another possibility is that the end-tidal O2 overestimated "alveolar" O2 during sleep, and so overall alveolar O2 was lower than the regulated end-tidal value, thus causing a lower saturation. Against this possibility is the observation that the increase in PETCO2 during sleep was well recorded, and, as we used a mass spectrometer, the dynamic characteristics for the measurements of CO2 and O2 would have been identical.
In addition to the apparent modest change in mean saturation during sleep, there were some values that appeared to indicate a much greater transient fall in saturation. These low values appeared mostly, but not exclusively, during sleep. Our impression is that these values were artifacts arising during periods when there was a poor signal from the pulse oximeter. They occurred more commonly during sleep, as, during periods of sleep, we were unable to ask the subject to reposition the finger probe. It is also possible that shorter periods of poor signal could underlie the small changes in mean saturation during sleep referred to above.Acid-base status during protocol P.
Although there was a change in calculated arterial pH in
protocol P, no compensation for this
change was detected in the acid-base status of the blood. This lack of
change in the standard HCO3 concentration 48 h after the induction of hypoxia is consistent with
previous observations by others (23). It is also consistent with the
notion that the early stages of VAH occur without the need for
compensatory changes in blood acid-base status generated by renal
excretion of HCO3. However, this does not rule out effects of renal compensation later in VAH. Nor does it
have any bearing on changes in cerebrospinal fluid
HCO3 concentration.
Persistent hyperventilation after relief of hypoxia. The observation that hyperventilation persists for some considerable time after return from high altitude is long standing (8), and some of this effect almost certainly is related to a slow reversal of the acid-base changes induced by residence at altitude. However, the results from the present study suggest that acid-base adjustment cannot be the sole mechanism that underlies this slow return, since the return to baseline was also slow after the isocapnic exposure. Indeed, the isocapnic and poikilocapnic exposures did not differ in this respect, a finding consistent with an earlier report from our laboratory in relation to shorter (8-h) periods of exposure and recovery from hypoxia (24).
In the present study the persistent hyperventilation was generated by an increase in the slope of theE-PETCO2 relationship without any concurrent leftward shift of the intercept of
this relationship with the
PETCO2 axis. However, from studies at altitude, it has generally been accepted that there is an
increase in the slope of the hyperoxic/euoxic
E-PETCO2 relationship and a leftward shift of the intercept (4, 12, 19, 20). One
possible interpretation of these two sets of findings is that the
increase in slope begins early in VAH and does not require alkalosis
(although this does not rule out further changes later in VAH) but that
the changes in intercept require a longer duration of hypoxia, a more
intense level of hypoxia, or a shift in the acid-base status of the blood.
In a number of previous studies,
PETO2 and
PETCO2 have been manipulated
together, and it may be useful to compare these with the present
study. Eger et al. (9) investigated in four subjects the effects of
holding PETCO2 at various levels over an 8-h period with and without hypoxia. They detected a
significant increase in the slope of the euoxic
E-PETCO2 relationship after experiments involving hypoxia if these values were
compared with measurements made before the hypoxic exposure. This
result is consistent with the present study. This increase did not
occur in experiments that did not involve hypoxia. However, the results
are not entirely clear cut, inasmuch as the increase in slope was not
significant if the slopes after hypoxic experiments were compared with
those after experiments not involving hypoxia.
In addition to these results with respect to the slope of the
E-PETCO2
relationship, Eger et al. (9) also reported a leftward shift of the
E-PETCO2
relationship that was related to the degree of hypocapnia but was
always greater if hypoxia was present rather than absent. This finding
appears consistent with the result of a study by Dempsey et al. (7) of
26 h of hypocapnia with or without hypoxia. In the study by Dempsey et
al., arterial PCO2 was reduced after
both exposures, but the reduction was greater after hypoxic hypocapnia than euoxic hypocapnia. Although these findings appear to contrast somewhat with those of the present study, the comparisons should not be
drawn too tightly. First, the degree of hypocapnia (obtained in general
by voluntary hyperventilation) employed in both studies to obtain these
results was far greater than that observed in protocol
P in our study. Second, Eger et al. defined the shift in relation to an arbitrarily chosen level of
E of 15 l · min1 · m2,
whereas in our study it was defined in relation to the intersection of
the
E-PETCO2
relationship with the PETCO2 axis. Third, the study by Dempsey et al. did not provide any
information on the slope of the
E-PETCO2
relationship, and therefore it is difficult to know whether the shift
in PCO2 caused by the sustained
hypoxia resulted from a change in slope or a change in intercept.
In a study comparing 100 h of poikilocapnic hypoxia with 100 h of
hypoxia with added inspired CO2,
Cruz et al. (6) were unable to demonstrate a change in the slope of the
E-PETCO2 relationship, although a trend is evident in their data. They did
report a significant reduction in the intercept of the
E-PETCO2 relationship with the PETCO2
axis, but only in the case of poikilocapnic hypoxia, and only after 75 h. The absence of any change within 48 h is compatible with the results
from the present study.
Comparisons between results in humans and those from animal studies
need to be drawn with care because of the very different time courses
observed for VAH between different species (1). Engwall and Bisgard
(10) investigated the period after 4 h of whole body isocapnic and
poikilocapnic hypoxia in goats, which is sufficient time for complete
acclimatization in this species. Persistent hyperventilation was
observed after poikilocapnic hypoxia but not after isocapnic hypoxia.
The hyperventilation was associated with a leftward shift of the
intercept of the
E-PETCO2 response curve with the
PETCO2 axis. Because these
features did not occur after isocapnic hypoxia, the authors
concluded that the effect was dependent on a respiratory alkalosis
developing during the hypoxic exposure. These findings, when compared
with ours, suggest that there may be qualitative differences between goats and humans with respect to this response. However, the authors did observe a significant increase in the slope of the
E-PETCO2 response after isocapnic hypoxia in keeping with the present study.
Weizhen et al. (25) studied isocapnic hypoxia in awake goats, where a
separate perfusion system was employed to keep the carotid body euoxic
and eucapnic. They did not find any persistent hyperventilation after
the hypoxic exposure, nor did they find any change in the slope of the
E-PETCO2
relationship. These results, together with those of Engwall and Bisgard
(10), suggest that in goats the increase in slope of the
E-PETCO2 relationship may require carotid body hypoxia and that it is not generated by central nervous system hypoxia.
Progressive increase in AHVR. Several investigators have reported that AHVR increases with exposure to high altitude (12, 13, 22, 26). The study of Howard and Robbins (15) demonstrated that 8 h of isocapnic hypoxia can cause a progressive increase in AHVR, and the present study has now extended this finding to 48 h, a time scale more commonly associated with VAH in humans.
These results are in some contrast to those of Cruz et al. (6), who found that, for hypoxic exposures with added inspired CO2, there was no significant progressive effect of the exposure on AHVR. Interpretation of their results is difficult, inasmuch as only four subjects were studied and it is not entirely clear at which PETCO2 the measurements of hypoxic sensitivity were made in the experiments in which CO2 was added. Experiments in awake goats have produced results that are broadly consistent with ours in humans (11) and, in addition, have provided good evidence to link the response to a process at the carotid body. In particular, an increase in hypoxic sensitivity has been observed in studies of sustained hypoxia isolated to a carotid body of goats maintained systemically euoxic and isocapnic (3), whereas Weizhen et al. (25) observed no change in hypoxic sensitivity with sustained central nervous system hypoxia. Hypercapnia isolated to a carotid body did not produce VAH (2). Taken together, these findings suggest that the mechanism for the rise in hypoxic sensitivity during VAH is caused specifically by hypoxia at the carotid body. Respiratory alkalosis was not required to generate these effects.| |
ACKNOWLEDGEMENTS |
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We acknowledge the skilled technical assistance of D. O'Connor and thank the volunteers for enthusiastic participation in the study.
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FOOTNOTES |
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This study was supported by the Wellcome Trust. J. G. Tansley is a Medical Research Council Student and M. J. Poulin is supported by a postdoctoral fellowship from the Heart and Stroke Foundation of Ontario (Grant F3555).
Address for reprint requests: P. A. Robbins, University Laboratory of Physiology, Parks Rd., Oxford OX1 3PT, UK.
Received 19 August 1997; accepted in final form 28 July 1998.
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REFERENCES |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Dempsey, J. A.,
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