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Respiratory and Sleep Disorders Unit, Repatriation General Hospital, Daw Park, Adelaide, South Australia 5041, Australia
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Sajkov, Dimitar, Alister Neill, Nicholas A. Saunders, and R. Douglas McEvoy. Comparison of the effects of sustained isocapnic
hypoxia on ventilation in men and women. J. Appl.
Physiol. 83(2): 599-607, 1997.
Sleep-related
respiratory disturbances are more common in men than in premenopausal
women. This might, in part, be due to different susceptibilities to the
respiratory depressant effects of hypoxia. Therefore, we compared
ventilation during 10 min of baseline room-air breathing and 20-min
sustained isocapnic hypoxia (fractional inspired
O2 = 11%, arterial saturation of
O2 
80%) followed by 10 min of
breathing 100% O2 in 10 normal men and in 10 women in the follicular phase of the menstrual cycle. Control measurements were made during two transitions from room air (10 min) to 100% O2 (10 min) and
averaged. Inspired minute ventilation
(
I) after
2 min of hypoxia was the same in men and women [131 ± 6.1%
baseline for men, 136 ± 7.7% baseline for women; not significant
(NS)] and declined to the same level after 20 min (115 ± 5.0% baseline for men, 116 ± 6.6% baseline for women; NS)
associated with a similar decline in inspiratory time and tidal volume.
Breathing frequency did not change.
I decreased transiently during subsequent 100%
O2 breathing in both men and women, associated with reduced frequency and duty cycle and increased expiratory time. The fall in
I was
significantly greater than that observed during control hyperoxia
experiments in men but not in women. We conclude that ventilatory
responses to sustained isocapnic hypoxia do not differ between awake
healthy men and women in the follicular phase of their menstrual cycle.
However, after termination of isocapnic hypoxia, men appear to depress their ventilation to a greater degree than women.
hyperoxia; control of breathing; gender
INTRODUCTION DURING SLEEP, there is an increased prevalence of
breathing disorders, such as snoring and sleep apnea syndromes, in men
compared with women (25, 34). Exogenous factors such as smoking and alcohol consumption may contribute to this gender bias. However, gender
differences in upper airway anatomy (8), physiological control of upper
airway muscles (26), and ventilatory responses to chemical stimuli may
also be important.
Hypoxia in the range of 70-90% arterial saturation of
O2
(SaO2) is a strong respiratory
stimulant. However, sustained isocapnic hypoxia for 20-30 min
produces a biphasic ventilatory response in which an early stimulatory
phase is followed by a roll-off or reduction of
ventilation toward baseline values (4, 12, 13, 29, 30). Some
investigators (5, 16, 20) have shown that, on cessation of hypoxic
breathing, an immediate suppression of ventilation occurs below
baseline values. Ventilatory depression during and after a
sustained hypoxic stimulus is thought to occur because of the release
of inhibitory neurotransmiters and neuromodulators, such as
We are unaware of previous studies that have compared the effects of
sustained isocapnic hypoxia in men and women. Although a number of
studies have investigated the influence of gender on the ventilatory
responses to progressive, short-term (5-10 min) isocapnic hypoxia,
no consistent findings have emerged. In the awake state,
women compared with men have been reported to have lower (32), higher
(1), and equal (19, 27) hypoxic ventilatory response.
However, the ventilatory response to progressive short-term hypoxia has
been found to be more depressed in men than in women after alcohol
consumption (23) and during non-rapid-eye-movement sleep (31). We
hypothesized that men might also be more susceptible to the ventilatory
depressant effects of sustained isocapnic hypoxia. Therefore, in the
present study, we compared the ventilatory responses to sustained (20 min) isocapnic hypoxia in awake healthy men and women.
METHODS Subject Selection
-aminobutyric acid and endogenous opioids (13). Hypoxia-induced depression of ventilation is possibly relevant to the pathogenesis of
sleep-disordered breathing because it carries the potential to
exaggerate sleep hypoventilation. Also, an undershoot of respiratory drive immediately posthypoxia is a potential cause for ventilatory instability and central or obstructive apneas (2, 15).
Study Design
Each subject underwent a control study followed by an experimental (sustained isocapnic hypoxia) study. These were conducted on separate days in 18 of 20 subjects. In two subjects, the experiments were conducted on the same day, and at least 20 min separated the studies.Subjects were asked to report to the laboratory at ~1000, after eating a light breakfast and after refraining from alcohol and caffeine for at least 8 h. All subjects were studied awake in a soundproof room separate from the monitoring room where physiological signals were recorded and the investigators manipulated the inspired gases (see Gas delivery). Subjects were seated comfortably, listened to relaxing music through headphones, and were observed by video camera. The temperature in the laboratory was controlled and held constant at 21°C.
To confirm that subjects remained awake during the experiments, continuous recordings of electroencelphalograms (EEG; C3-A1 placement), electrooculograms (EOG), and electromyograms (EMG) were performed. Continuous electrocardiogram recordings were also made.
Isocapnic hypoxia. Sustained isocapnic hypoxia experiments consisted of 10 min of baseline room-air breathing, followed by the rapid introduction of hypoxia (3 breaths of 100% N2, followed by an inspired gas concentration of 11% O2-89% N2) that was continued for 20 min. Isocapnic conditions (± 1 mmHg) were maintained during hypoxia by a variable manual bleed of CO2 into the inspiratory side of the breathing circuit. After 20 min of isocapnic hypoxia, 100% O2 was administered for 10 min. The 100% O2 was given to achieve a rapid increase in alveolar PO2, thereby allowing changes in posthypoxic ventilation to be compared between subjects independent of individual differences in the time required to wash out the hypoxic gas from the lungs. The addition of CO2 to the inspiratory line was ceased immediately on switching to 100% O2 breathing. Control. Control measurements were performed to establish the effects of hyperoxia (100% O2) on ventilation. This was necessary to separate the known transient ventilatory depressant effect of hyperoxia per se (9, 11) from any ventilatory depressant effect of sustained hypoxia on baseline ventilation. In each control experiment, 10 min of baseline room-air breathing were followed by 10 min of 100% O2 breathing. No attempt was made to control end-tidal PCO2 (PETCO2) in control experiments. At the end of the hyperoxic period, subjects were given five breaths of N2 before switching back to room-air breathing. Two sets of control measurements were undertaken sequentially in each subject to increase the number of observations of the normoxia-hyperoxia transition, and the results were averaged. Gas delivery. Gas mixtures were introduced to the inspiratory side of the breathing circuit through a five-way Gatlin-Shape valve (series 2440C, Hans Rudolph, Kansas City, MO). This valve has a single outlet, which was connected to the inspiratory tubing, and four separate inlets, three of which were attached to reservoir bags containing 100% O2, 100% N2, or 11% O2-89% N2 mixture, respectively. The fourth inlet was open to room air. The inlets were opened or closed rapidly and silently by balloon inflation, using a pressure source and a system of solenoid valves that was controlled remotely from the monitoring room.Measurements
Ventilation. Ventilation was measured by using a tightly fitting Downs full-face mask (dead space = 75-100 ml, depending on facial configuration), with built-in unidirectional valves and an external CO2 leak detector. A pneumotachograph (PT36, Erich Jaeger, Germany) was placed in the inspiratory side of the circuit to measure flow, from which tidal volume (VT) was recorded by electronic integration. The resistance of the inspiratory circuit was <1 cmH2O · l
1 · s.
Respiratory frequency (f), inspired minute ventilation
(I), and
indexes of ventilatory timing [i.e., duration of the respiratory cycle (TT), inspiratory time
(TI), expiratory time
(TE), inspiratory fraction of
respiration
(TI/TT),
and inspiratory flow rate
(VT/TI)] were computed and averaged for selected 1-min periods during
experiments (see Data Analysis and
Statistics). Minute ventilation and
VT were measured for every
breath, but to enable the large quantity of data to be handled
reasonably, measures of ventilatory timing were obtained by sampling
alternate breaths when f was 
10 breaths/min. When breathing f fell
below 10 breaths/min, all breaths were sampled.
Because a pneumotachograph was used for measurement of flow and volume,
it was necessary to correct the measurements of inspired gas volume for
the different viscosities of the gas mixtures used. The major change in
inspired gas viscosity in our experiments occurred during
O2 breathing. Correction factors
used were derived by repeated 1-liter calibrations (1-liter calibration
syringe, Hans Rudolph) with the use of the various gas mixtures
employed in the experiments. The volume signal, using 1-liter of room
air as the calibrating signal, was assigned a value of unity, and the
derived correction factors for the other gas mixtures are shown in
Table 1. These experimentally determined
correction factors were within 2% of those determined theoretically by
using Poiseuille's equation.
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Data Analysis and Statistics
The Student's t-test was used to compare baseline variables between men and women, and the
2 test was used to compare
categorical variables. Ventilatory parameters (I,
VT, f,
TT,
TI,
TE,
TI/TT,
and
VT/TI)
were calculated for minutes 2,
4, 6,
8, and
10 of the 10-min baseline periods and then averaged. Subsequent results were expressed in absolute terms and
as a percentage of the corresponding average baseline value. Ventilatory parameters were measured for minutes
1, 2,
3, 5,
10, 15, and
20 during sustained isocapnic hypoxia
and minutes 1,
2, 3,
5, and
10 during hyperoxic breathing (either
posthypoxia or during control experiments). Data obtained at these
times were used to graphically display the results.
To examine differences in the biphasic ventilatory response during sustained isocapnic hypoxia between the genders, we compared parameters of ventilation at baseline and at early (2 min) and late (20 min) hypoxia within and between the sexes by using two-way analysis of variance (ANOVA). In contrast to the ventilatory response during sustained isocapnic hypoxia, relatively little is known about the behavior of ventilation after sustained hypoxia. Therefore, to examine for differences after sustained isocapnic hypoxia, we included all data points (i.e., posthypoxia minutes 1, 2, 3, 5, and 10). Data from a given experimental intervention were first subjected to a one-way ANOVA for repeated measures to determine whether there were statistically significant differences observed with respect to time. Two-way ANOVA for repeated measures was used to determine whether, within a gender, there were differences between hyperoxic breathing after sustained isocapnic hypoxia vs. hyperoxic breathing after room-air breathing. Two-way ANOVA was also used to determine whether there were differences between genders within the same experimental intervention. When the F statistic reached statistical significance, pairwise comparisons were performed with the use of the Newman-Keuls procedure.
RESULTS
There was no difference in age, body mass index, smoking habits, and
respiratory function between male and female volunteers (Table
2). Small, but statistically significant,
differences were found for blood pressure, hemoglobin levels, and
baseline I,
consistent with the known physiological differences between men and
women for these variables.
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During Sustained Isocapnic Hypoxia
The same hypoxic stimulus was produced in both men and women. The lowest SaO2 was achieved at the end of the hypoxic period [SaO2 = 79 ± 1.5% in men; 79 ± 1.0% in women; not significant (NS)], and the SaO2 curves (Fig. 1) were virtually superimposed for men and women. Isocapnic conditions were maintained (PETCO2 within 2-3 Torr) throughout the period of sustained hypoxia in both men and women (Fig. 1), with exception of the first minute of hypoxia in women, when a small fall in PETCO2 occurred. PETCO2 was slightly lower in women (P < 0.05) during baseline room-air breathing and throughout the experiment.
) and women
(
) during isocapnic hypoxia. Bars, SE.
P < 0.05 compared with
room-air baseline.
Hypoxia resulted in an early increase in
I in men and
women, followed by a roll-off in
I during
hypoxia (Fig. 2, Table 3). Expressed as a percentage of respective
baseline values, the magnitude of these changes did not differ between
men and women (Table 3). The acute hypoxic ventilatory response (HVR) calculated during the second minute of hypoxia and expressed as a
change in ventilation vs. change in saturation per square meter of body surface area (BSA)
(
I/SaO2/BSA)
was identical in men and women (0.17 ± 0.04 l · min1 · %SaO21 · m2).
)
and women ().
I, inspiratory
ventilation. Bars, SE.
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We found that isocapnic hypoxia induced a significant early rise in
VT,
TI, and the duty cycle
(TI/TT)
in both men and women, with no significant change in breathing f,
TE, and
VT/TI.
The subsequent roll-off of
I during
sustained hypoxia was due to a fall in
VT,
TI, and
TI/TT
that was similar in magnitude for men and women (Table 3). The duty
cycle was shorter in women compared with men during both room-air
breathing and hypoxia.
After Sustained Isocapnic Hypoxia
Ventilation in men and women in the posthypoxic periods is shown in Fig. 3 and compared with the corresponding changes in ventilation during control hyperoxia experiments (shaded areas). Transient depression ofI
(P < 0.05 compared with baseline) was observed at 1 min posthypoxia and during the first minute of the
control hyperoxia experiments in both men and women (Fig. 3B). During control hyperoxia
experiments, there was a trend toward a subsequent increase in
I,
VT, and f at 3 min that was not sustained (Fig. 3, B-D). In men, the
ventilatory depression observed at 1 min posthypoxia was significantly
greater than for the corresponding period during the control hyperoxia
experiment. This difference was not seen in women. In the first minute
after hypoxia, TE was increased
significantly compared with the corresponding hyperoxia control values
in both men and women (Fig. 3F).
This increase in TE after
hypoxia was associated with a reduction in duty cycle (Fig.
3G) in men and women and a
significant fall in breathing f (Fig.
3D) at 1 min in men. During control
hyperoxia experiments, there was no change in timing variables in men
or women, with the exception of a small increase in
TI in men at 1 min.
) are means ± SE
(bars) obtained after transition from 20 min of sustained isocapnic
hypoxia to hyperoxia (i.e., hypoxia experiments).
A: ETCO2,
end-tidal CO2.
B:
I, inspiratory
minute ventilation. C:
VT, tidal volume.
D: Freq, frequency.
E:
TI, inspiratory time. F:
TE, expiratory time.
G:
TI/TT,
ratio of TI to total time.
H: ratio of
VT to
TI.
P < 0.05 compared with
baseline for control experiments.
* P < 0.05 compared with
baseline for hypoxia experiments. 
P < 0.05 control vs.
hypoxia experiments.
End-tidal CO2 (Fig.
3A) did not change significantly
from baseline levels at 1 min posthypoxia and during the first minute of the control hyperoxia experiments in men and women, and, therefore, could not explain the transient depression of
I that was
observed in these different protocols. No attempt was made to maintain isocapnic conditions during hyperoxic breathing, and
PETCO2 was observed to fall
in both men and women after about the third minute in both protocols
(Fig. 3A).
DISCUSSSION
The main findings of this study were that the acute (2-min) response to
isocapnic hypoxia and the subsequent roll-off in
I during
hypoxia (20 min) were the same in men and women, whereas in the
immediate posthypoxia period there was a transient depression of
in men, exceeding that observed during
control hyperoxia experiments, that was not observed in women. This
suggests that men may be more susceptible to posthypoxic ventilatory
depression, despite a similar pattern of ventilatory response to
sustained isocapnic hypoxia in awake healthy men and premenopausal
women in the follicular phase of their menstrual cycle.
Ventilatory Changes During Sustained Isocapnic Hypoxia
Both genders showed virtually identical biphasic responses to sustained isocapnic hypoxia (early augmentation ofI followed by
roll-off or decrease in
I), with the
roll-off in I
being due to a fall in VT and a
fall in TI and the
TI/TT.
This biphasic ventilatory response to sustained isocapnic hypoxia is
similar to that reported in previous studies (12, 16, 24). The changes that we observed in ventilatory timing during the acute response and
subsequent roll-off (e.g., increase and then roll-off in
TI and
TI/TT
without a change in breathing f) are similar to those reported
previously (12, 16, 24). The difference between the present study and
these earlier studies is that we did not observe an increase in
respiratory drive during hypoxia, as assessed by increased
VT/TI.
Rather, the increase and subsequent decrease in
VT appeared to be associated
mainly with changes in TI. This difference could
potentially be explained by the different route of breathing employed.
Two of these earlier studies (12, 16) used mouth breathing and
noseclip, which are known to be associated with increased ventilatory
drive (10). Furthermore, it is possible that the use of a face mask,
rather than noninvasive methods such as inductive plethysmography, may
affect the pattern of ventilation during hypoxia.
Previous studies have indicated that administration of both female and male hormones may increase ventilation and ventilatory responsiveness to acute hypoxia. However, there is controversy about whether physiological gender differences in hypoxic responsiveness exist. The female hormone progesterone, particularly when combined with estrogen, has been shown to increase ventilation and the acute (i.e., 5-10 min) HVR in humans and experimental animals of either sex (18, 28). The male hormone testosterone also increases ventilation and the HVR, although its effects seem to result from an increase in metabolic rate (33).
Previous studies comparing the HVR between men and women have given
conflicting results. White et al. (32) described lower HVR in 10 premenopausal women compared with 12 healthy, age-matched men, whereas
Aitken et al. (1) reported higher HVR in 30 premenopausal women in
their follicular phase compared with 37 age-matched men. Other studies
found no gender differences in HVR (19, 27). Our results are in keeping
with these latter studies, with the early (2 min) HVR being virtually
identical in women and men (0.31 ± 0.07 and 0.33 ± 0.07 l · min1 · %SaO21,
women and men, respectively). The magnitude of the early (2 min)
increment in
I
(31-36%) in the present study was lower than that reported in
some other studies of sustained isocapnic hypoxia (12, 20, 29) but
similar to another (16). This probably reflects the slower
induction of hypoxia in our study (SaO2 of ~90% during the second
minute) compared with the studies of others (12, 29) where an
SaO2 of ~80% was achieved within the
first 2 min. However, the acute hypoxic ventilatory response, expressed
as percent change in SaO2 (0.31 ± 0.07 and 0.33 ± 0.07 l · min1 · %SaO21
for women and men, respectively) was also lower than reported in most
earlier studies [e.g., 0.46-1.0, 0.69, and 1.47 l · min1 · %SaO21
(see Refs. 32, 28, 27, respectively)]. These differences may in
part be due to methodological differences. Our subjects breathed
through the nose and used a face mask, whereas the subjects in the
above studies breathed by using a mouthpiece and noseclip. Acute HVR
has been shown to be higher during mouth breathing than during nasal
breathing (10). Our study is the first comparison of hypoxic
ventilatory responses in men and women during nasal breathing.
As shown in the present study, exposure to sustained isocapnic hypoxia
causes a roll-off over a period of 10-15 min to a new steady-state
level that is usually above the prehypoxic ventilation (12, 29, 30).
The mechanisms of ventilatory depression during sustained isocapnic
hypoxia remain unclear. Considerable evidence points to the
accumulation of inhibitory neurotransmiters (e.g., -aminobutyric
acid) in the brain during sustained isocapnic hypoxia (13), whereas
other evidence suggests that, at least in adult men, ventilatory
depression results from the effects of hypoxia on the peripheral
chemoreflex (3, 4, 17, 21).
The effect of gender on hypoxia-induced ventilatory depression has not, to our knowledge, been systematically studied before. In the present study, men and women demonstrated the same ventilatory decline during 20 min of sustained isocapnic hypoxia, caused by a fall in VT, rather than change in breathing f. Several earlier studies of sustained isocapnic hypoxia included both male and female volunteers (3-5, 12, 17, 21) but did not group data by gender. In four studies (3-5, 21) individual ventilatory responses were graphed, and in none of these studies was a gender difference in ventilatory roll-off apparent. In our study, the PETCO2 in women was slightly, but significantly, less than that in men throughout the experiment. Our intention in this study was to measure the acute hypoxic ventilatory response and subsequent ventilatory depression at the physiological set point of CO2, i.e., under eucapnic conditions. We did not, therefore, artificially increase the PETCO2 in women to match that in the men. It is possible that our results comparing the acute and prolonged responses to isocapnic hypoxia between men and women would have been different had we done so.
Ventilatory Changes After Sustained Isocapnic Hypoxia
The method we adopted to terminate hypoxia was to switch the subject abruptly to 100% O2 breathing, which was then continued for 10 min until the end of the experiment. This produced a rapid increase in saturation, thereby allowing the ventilatory off response to be compared between subjects independent of individual lung washout times. We also reasoned that sudden withdrawal of peripheral chemoreceptor drive would allow any central depressant effects of sustained isocapnic hypoxia to be better observed and compared between men and women. However, hyperoxia without preceding hypoxia has been shown to produce immediate short-term ventilatory depression (9, 11, 22). Recent studies have shown that ventilation increases during sustained hyperoxia (6, 7). Therefore, it was important to conduct a control experiment to measure the effects of a sudden switch from breathing room air to breathing 100% O2, to establish the magnitude of any ventilatory undershoot or depression related to preexisting hypoxic conditions, and to control for the effects of any subsequent augmentation of ventilation during sustained hyperoxia. Room-air to hyperoxia transitions. Hyperoxia (100% O2 breathing) after room-air breathing produced an ~15% decrease inI in both men
and women in the first minute, which was similar in magnitude to the
8-12% depression reported previously in similar experiments (9,
11, 22). In contrast, Holtby et al. (20) were unable to show a
significant posthyperoxia depression of ventilation, possibly due to
their measurement technique (i.e., moving average of 7 breaths,
searching for nadirs). The small transient decrease in
I that we
observed was not associated with statistically significant changes in
respiratory timing or effort variables. In the present study, 3 min
after the room-air to hyperoxia transition, there was a slight increase in I above
baseline (in women) and an increase in
VT (in men) that was not
sustained. During these control experiments, end-tidal CO2 was not controlled, and there
was a small progressive fall in
PETCO2, particularly after 5 min. These changes are consistent with previous reports of increased
ventilation (6, 20) and reduced
PETCO2 (6, 9) during
sustained poikilocapnic hyperoxic breathing. These changes are thought
to be due to stimulation of medullary chemoreceptors by an increase in
cerebrospinal CO2 concentration,
resulting from the combined effects of increased oxyhemoglobin levels
during O2 breathing (Haldane
effect) and a reduction of cerebral blood flow (6).
Hypoxia-hyperoxia transitions.
In posthypoxia experiments, there was a transient fall in
I in the first
minute of O2 breathing, which, in
contrast to control experiments, was associated with a prolongation of
TE and a decrease in respiratory
duty cycle. The 1-min posthypoxia fall in
I appeared to
be greater in men than in women and was significantly different from
hyperoxic control values in men. Previous studies, predominantly of
male subjects, have shown similar degrees of ventilatory depression after sustained isocapnic hypoxia (5, 16, 20). The changes in
posthypoxia TE
that we observed were similar to those reported by Georgopolous et al.
(16) after 25 min of sustained isocapnic hypoxia and by Badr et al. (2)
after 5 min of sustained isocapnic hypoxia in non-rapid-eye-movement
sleep. Unlike those studies, we did not find a decrease in
VT posthypoxia. These changes in I and
respiratory timing cannot be explained on the basis of changes in
end-tidal CO2, because
PETCO2 was unchanged for the
first 3 min posthypoxia.
The finding that there was no gender difference in ventilatory
response, and particularly in the roll-off phenomenon, during sustained
isocapnic hypoxia but that differences were observed in posthypoxic
ventilatory depression may appear inconsistent. However, these two
manifestations of hypoxic ventilatory depression may be caused by
different neurophysiological/neurochemical phenomena. The hypoxic
"on-response" and roll-off appear to be caused by changes in
TI and possibly respiratory
drive, whereas the posthypoxia undershoot appears, from our study and
previous work (2, 16), to be associated with changes in
TE. In addition, it has been shown that adenosine antagonism with aminophylline seems to have a
greater effect on sustained isocapnic hypoxia ventilatory roll-off than
on posthypoxic undershoot (16).
PETCO2 did not increase
during the transient falls in
I
observed after the normoxia-hyperoxia and hypoxia-hyperoxia transitions. We have no direct experimental evidence to explain this
apparent discrepancy. The fact that it was observed in both experimental settings makes it unlikely that it was due to a reduction in metabolic rate after sustained hypoxia; rather, it was linked to
O2 breathing.
Cardiac output is known to fall acutely during hyperoxic breathing
(14). Therefore, we believe that the most likely explanation for
isocapnic conditions being maintained in the presence of a transient
fall in I is
that hyperoxia caused an immediate fall in cardiac output and therefore
an immediate fall in CO2 flow to
the lungs.
Also of note was that baseline
PETCO2 was lower in women
than men and remained so throughout the experiments. In a study of
resting ventilation, metabolic rate, and hypoxic and hypercapnic
ventilatory responses in 67 subjects, Aitken et al. (1) showed that
women had lower metabolic rates (even after correction for BSA) but
higher baseline ventilatory drives and lower
PETCO2 than men. Women were
studied in the follicular phase of the menstrual cycle, as in our
study, so the difference was not a luteinizing effect. Therefore, it is
possible that increased ventilatory drive in women may protect them
from posthypoxic respiratory depression.
We conclude that awake healthy men and women in the follicular phase of
their menstrual cycle show the same biphasic response to sustained
isocapnic hypoxia. However, posthypoxic ventilatory depression is
significantly greater compared with hyperoxic control measurements in
men but not in women. The tendency for ventilation to return gradually
to baseline levels on sudden removal of a respiratory stimulus is
thought to be an important mechanism of maintaining respiratory
stability (2, 15). Our findings suggest that after removal of a
sustained hypoxic stimulus the ventilatory depressive effects of
hypoxia are more prominent in men, possibly rendering them more
susceptible to unstable patterns of breathing.
ACKNOWLEDGEMENTS
We acknowledge the professional assistance of Robin Woolford, Biomedical Engineering Department Repatriation General Hospital, Daw Park, for building the breathing circuits and controllers for this study.
FOOTNOTES
Address for reprint requests: D. Sajkov, Sleep Disorders Unit, Repatriation General Hospital, Daw Park, Adelaide, South Australia 5041, Australia (E-mail: mnds{at}flinders.edu.au).
Received 23 December 1996; accepted in final form 11 April 1997.
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