J Appl Physiol 95: 545-554, 2003.
First published April 25, 2003; doi:10.1152/japplphysiol.01051.2002
8750-7587/03 $5.00
Ventilatory response of the cat to hypoxia in sleep and wakefulness
Andrew T. Lovering,1
Witali L. Dunin-Barkowski ,1,2
Edward H. Vidruk,3 and
John M. Orem1
1Texas Tech University School of Medicine,
Department of Physiology, Lubbock, Texas 79430-6551;
2Information Transmission Problems Institute, Russian
Academy of Science, Moscow 101447, Russia; and
3University of Wisconsin Medical School, Department of
Population Health Sciences, Madison, Wisconsin 53705-2368
Submitted 18 November 2002
; accepted in final form 23 April 2003
 |
ABSTRACT
|
|---|
This study characterized ventilation, the airflow waveform, and
diaphragmatic activity in response to hypoxia in the intact adult cat during
sleep and wakefulness. Exposure to hypoxia for up to 3 h caused sustained
hyperventilation during both wakefulness and sleep. Hyperventilation resulted
from significant increases in minute ventilation due to increases in both
tidal volume and frequency. Diaphragmatic activity changed significantly from
augmenting activity with little postinspiratory-inspiratory activity (PIIA) in
normoxia to augmenting activity with increased PIIA in hypoxia. The increase
in PIIA was least in rapid eye movement sleep. These changes in diaphragmatic
activity were associated with changes in airflow waveforms in inspiration and
expiration. We conclude that the ventilatory response to hypoxia involves a
change in the output of the central pattern generator and that the change is
dependent in part on the state of consciousness.
airflow waveform; periodic breathing; diaphragmatic activity; postinspiratory-inspiratory activity; rapid eye movement sleep
OUR CONCERN IN THIS STUDY was the pattern of breathing of
intact, unanesthetized cats exposed to hypoxia. Although we were interested in
overall ventilation, an interest sparked by disagreements among published
studies (1,
14,
22,
27), our primary interest was
in the form of the individual breaths. For example, we wanted to know whether
inspiratory airflow and diaphragmatic activity had augmenting forms in hypoxia
as they do in normoxia. Furthermore, we wanted to know how state of
consciousness affected diaphragmatic activity and thus airflow waveforms of
inspiration and expiration. This information is essential for understanding
changes in output of the respiratory central pattern generator in response to
hypoxia. Therefore, we analyzed ventilation, diaphragmatic activity, and the
form of inspiratory and expiratory airflow during normoxia and hypocapnic
hypoxia in sleep and wakefulness. The results show that the airflow waveform
is indeed altered in hypoxia, as is the pattern of diaphragmatic activity.
They show also that these changes are superimposed on state-specific breathing
patterns.
|
MATERIALS AND METHODS
|
|---|
Subjects. Five adult cats (3.2–5.3 kg) were prepared for
recordings of electroencephalographic (EEG), pontogeniculo-occipital (PGO),
and diaphragmatic electromygraphic (EMG) activity. Tracheal fistulas were
created, and headcaps containing a connector for electrodes were attached to
the animals' skulls. The headcap contained also standoffs that were used to
immobilize the animal's head during recordings. The animals recovered from
surgery for 1 mo before experimentation. After recovery, they were adapted to
the experimental apparatus. The Animal Care and Use Committee of Texas Tech
University School of Medicine approved all surgical and experimental
procedures.
Surgical procedures. The animals were initially anesthetized with
acepromazine maleate (2.5 mg im) and ketamine (17 mg/kg im). Surgery was
performed under antiseptic conditions. A midline incision was made from below
the cricoid cartilage to just above the suprasternal notch, and the
sternothyroid, sternohyoid, and sternomastoid muscles were retracted to expose
the trachea. The trachea was opened longitudinally, and the cut edges of the
rings were sewn to the skin margins on the corresponding side to create a
fistula. Anesthesia was then maintained by administration of 1–2%
halothane in O2 through the trachea.
The animal was placed in a supine position, and an incision was made caudal
to the costal margin from the xiphoid process to the midaxillary line. Four
EMG electrodes (Teflon-coated multistranded stainless steel wires; Cooner AS
632) were implanted within crural and semitendinous regions of the right
diaphragm. The electrodes were placed as medially as possible to avoid
intercostal muscle activity contamination. The EMG wires were run
subcutaneously to the back of the neck, where they were routed to the
skull.
The animal was placed in a stereotaxic frame, and a midline incision
exposed the dorsal skull. EEG electrodes [4-40 stainless steel screws with
multistranded Cooner (AS 632) stainless steel leads] were screwed into the
skull over medial occipital and parietal cortices bilaterally. PGO electrodes
were constructed from stainless steel insulated wires (0.006-in. diameter)
twisted into a tripolar electrode. The insulation was stripped from the tips
for a distance of 
0.5 mm, and the tips were separated by 0.5–1.0 mm
vertically. Two tripolar electrodes, one in each hemisphere of the brain, were
implanted stereotaxically at coordinates A6.4, L10, and H+2.5. These are the
coordinates of the fibers of the optic tract where they enter the lateral
geniculate body of the thalamus. PGO wave recordings are optimal when the
electrode tip in these fibers is referred to an electrode in the overlying
lateral geniculate body.
EEG and PGO electrodes and 4-40 anchor screws were cemented to the skull. A
prefabricated headcap containing standoffs for immobilization of the head was
fixed to the skull with dental cement. Gold cinch pins were crimped to the
ends of the diaphragmatic, EEG, and PGO electrode wires and were inserted into
a connector block. The connector block was then attached to the headcap.
Recording procedures and exposure to hypoxia. On nights before
recording sessions, the animals were housed in a cold (0°C) environment to
prevent rapid eye movement (REM) sleep and therefore to consolidate REM sleep
the following day. During recordings, the trachea was intubated with a 4.0-mm
endotracheal tube that was attached to a Validyne pneumotachograph. Total dead
space of the tracheal tube and pneumotachograph was 8 ml, which is
approximately equal to the dead space of the upper airway. Pressure levels in
the tube were measured by using a volumetric pressure transducer. Tidal
O2 and CO2 were measured with an O2 analyzer
(Beckman OM-11) and infrared CO2 analyzer (Beckman LB-2). Tidal
O2 and CO2 percentages; EEG, EMG, and PGO activity;
airflow; and intratracheal pressures were recorded on paper (Astro-Med 9500)
and on magnetic tape. Diaphragmatic activity was amplified with a Grass p511
amplifier set to pass frequencies from 0.3 to 30 kHz. Control conditions were
obtained with animals breathing room air in Lubbock, Texas (altitude 1,000 m).
Once control conditions were obtained, animals breathed a hypoxic gas mixture
(inspired O2 fraction = 10% O2 in N2;
alveolar Po2 = 63 Torr). In this study, CO2 levels were
always allowed to decrease as a function of ventilation (hypocapnic hypoxia).
Three cats breathed hypoxic gas for periods up to 3 h, and two cats breathed
hypoxic gas for a time sufficient to record all three states of consciousness.
Recording sessions lasted 4 h. Non-rapid eye movement (NREM) and REM
sleep and wakefulness were defined on the basis of standard EEG criteria
(17).
Data analysis. Diaphragmatic activity, PGO activity, EEG activity,
and airflow were digitized from analog tape records at 1,000 samples/s by use
of a National Instruments data acquisition board. For breath-by-breath
analysis, tidal volume (VT), inspiratory duration (TI),
and breath duration (TT) were derived from the airflow signal by
use of custom software. Expiratory duration (TE), frequency of
breathing (f), and minute ventilation
(
E) were calculated from the derived
parameters. Diaphragmatic activity was transformed to a rectified signal.
For qualitative analysis of airflow waveforms and diaphragmatic activity,
the respiratory cycles were divided into 1,000 bins, and the data for multiple
breaths were averaged over the bins. In wakefulness and NREM sleep, single or
multiple (n 
3) episodes of consecutive normal breaths (not
interrupted by augmented breaths and abnormalities in the airflow trace caused
by swallows, movement, coughs, or vocalizations) in the same state were
selected without regard to breath duration. In REM sleep, all the breaths for
the REM period were analyzed.
For quantitative analysis of diaphragmatic EMG, averaged activity was
divided into inspiration (I), the first half of expiration (E1), and the
second half of expiration (E2). Activity (arbitrary units) in each division
(I, E1, and E2) was summed and divided by the time of the corresponding
division to give activity/s. Baseline noise (activity/s) was subtracted from
that value. Because activity varied among animals, data were normalized in
each cat by expressing the activity as a ratio of the total mean diaphragmatic
activity per second during NREM sleep in normoxia.
Airflow waveform was quantitatively characterized breath by breath by using
an integral of the deviation of the actual waveform from a pair of fixed
waveform templates: the triangular and square waveform. The triangular
waveform template was constructed as two right triangles: one positive right
triangle (inspiration) and one negative right triangle (expiration) with the
right angles positioned at the transition from inspiration to expiration. The
square waveform template consisted of two square waves: one positive
(inspiration) and one negative (expiration). The template dimensions were
adjusted to the parameters of the actual waveforms. The duration of
TI or TE for the template was determined by the
TI or TE of the actual waveform. The areas
(VT) of the actual inspiratory and expiratory airflows were
normalized to a value of 1. The amplitudes of the template waveforms for
inspiration and expiration were selected to make the areas of the templates
also equal to 1. The integral of the absolute value of the difference between
the template waveforms and the actual waveforms was calculated to obtain
breath-by-breath values. Thus, the more closely a waveform resembled the
template waveform, the smaller the calculated value. Square-wave deviation and
triangular-wave deviation were calculated independently for inspiration and
expiration, which yielded four numbers for each breath. The inspiratory and
expiratory values for square-wave deviations and for triangular deviations
were averaged over multiple breaths, and mean values were used for analysis.
Equations for and a graphical representation of this method for examining
airflow waveforms are in the APPENDIX.
Paired t-test and a one-way ANOVA with Dunnett's correction for
multiple comparisons were used for statistical analysis. Results were
considered significant when P < 0.05.
|
RESULTS
|
|---|
Results reported here were obtained from five adult cats during 51
recording sessions.
Hypoxia-induced hyperventilation in wakefulness and sleep. Hypoxia
caused a sustained hyperventilation in quiet wakefulness and NREM and REM
sleep (Figs. 1,
2, and
3). We did not observe a single
instance of ventilatory depression in any of the cats in any of the sessions.
Hyperventilation was continuous, and end-tidal CO2 levels continued
to decrease throughout the recording period
(Table 1,
Fig. 1). Respiratory parameters
during wakefulness for a 3-h period of hypoxia in one animal (EDM) are
reported in Table 1. During
this 3-h recording period, VT, f, and
E were significantly increased, and
TI, TE, TT, and end-tidal CO2 were
significantly decreased (Table
1).
View larger version (42K):
[in this window]
[in a new window]
|
Fig. 1. Breathing during non-rapid eye movement (NREM) sleep in normoxia and
hypocapnic hypoxia. A: raw traces of airflow, tidal CO2%,
EEG, and pontogeniculo-occipital (PGO) waves during a 45-min exposure to
hypoxia in 1 cat. Arrow indicates the onset of hypoxia. a.u., Arbitrary units;
*, augmented breaths. B: breath-by-breath representation
of data in A (augmented and abnormal breaths removed). Dashed lines
indicate mean values in normoxia control. VT, tidal volume; f,
frequency of breathing; E, minute
ventilation; TTOT, total breath duration; TI,
inspiratory time; TE, expiratory time.
|
|
View larger version (58K):
[in this window]
[in a new window]
|
Fig. 2. Breathing during wakefulness (W) and NREM and rapid eye movement (REM)
sleep in normoxia (A) and hypocapnic hypoxia (B).
|
|
View larger version (15K):
[in this window]
[in a new window]
|
Fig. 3. Respiratory parameters during W and NREM and REM sleep in normoxia and
hypocapnic hypoxia. Data are from 5 cats. Number of breaths analyzed: W 21%
O2 (348), 10% O2 (410); NREM 21% O2 (514),
10% O2 (767); REM 21% O2 (886), 10% O2 (877).
Values are means ± SE. *Significance (P < 0.05),
paired t-test.
|
|
The pattern of breathing depended on the state of consciousness in both
normoxia and hypoxia (Figs. 2
and 3). In NREM sleep, compared
with wakefulness, f was low, VT was large, and there was little
variability. During REM sleep, compared with NREM sleep, f increased,
VT decreased, variability increased, and end-tidal CO2
decreased.
In hypoxia, state-specific patterns were maintained on a background of
hyperventilation. The hyperventilation was caused by a significant increase in
E in all states
(Fig. 3). The increase in
E was a result of a significant
increase in VT. The f was significantly increased only in NREM
sleep (Fig. 3). Changes in
VT were caused by increased initial airflow rates (Figs.
4,
5,
6,
7), increased peak airflow
rates (Figs. 1,
2, and
4,
5,
6,
7), and increased average
airflow that resulted from a change in the airflow waveform (Figs.
4,
5,
6,
7,
8).
View larger version (30K):
[in this window]
[in a new window]
|
Fig. 4. Airflow waveform and diaphragmatic activity (EMGDIA) in normoxia
(A) and hypocapnic hypoxia (B) during NREM sleep.
|
|
View larger version (11K):
[in this window]
[in a new window]
|
Fig. 5. Airflow waveform and diaphragmatic activity in wakefulness. Airflow
waveform in normoxia control (A) and 60–180 min of hypocapnic
hypoxia (B). Traces are averaged airflow waveforms and averaged
diaphragmatic rectified EMG from 1 cat. Numbers of breaths analyzed are as
follows: 13 in A; and 24, 31, and 42 (top, middle, and
bottom, respectively) in B. All data are plotted on the same
scale.
|
|
View larger version (12K):
[in this window]
[in a new window]
|
Fig. 6. Averaged airflow waveforms and averaged rectified diaphragmatic activity in
NREM and REM sleep in normoxia (21% O2) and hypocapnic hypoxia (10%
O2) in 1 cat. Number of breaths analyzed: NREM 21% O2
(82); NREM 10% O2 (172); REM 21% O2 (150); REM 10%
O2 (174). All data are plotted on the same scale.
|
|
View larger version (15K):
[in this window]
[in a new window]
|
Fig. 7. Airflow waveform deviation. A: averaged airflow waveforms during
NREM sleep in 1 cat. Number of breaths analyzed: 21% O2 (80); 10%
O2 (222). Dashed line is zero flow. B: breath-by-breath
plot of waveform factors (see APPENDIX) data in A.
|
|
View larger version (35K):
[in this window]
[in a new window]
|
Fig. 8. Analysis of airflow waveforms in normoxia and hypocapnic hypoxia.
A: deviation from triangular waveform. B: deviation from
square waveform. Data are from 5 cats. Numbers of breaths are listed in legend
for Fig. 3. Values are means
± SE. *Significance (P < 0.05), paired
t-test.
|
|
Airflow waveform in wakefulness and sleep. Airflow waveform was
analyzed in all five cats. In general, the typical triangular waveforms seen
during normoxia (Fig. 4 and
5A) became, within a
few breaths after the onset of hypoxia, more like a square waveform (Figs.
4,
5,
6). An example of the
breath-by-breath results obtained for one cat in NREM sleep in hypoxia and
normoxia is presented in Fig.
7. In hypoxia in all states, the waveforms in both inspiration and
expiration deviated significantly from the corresponding triangular template
(Figs. 7 and
8). The expiratory waveforms
more closely resembled a square-wave template, as did the inspiratory waveform
in wakefulness (Figs. 7 and
8). However, in NREM and REM
sleep the inspiratory airflow waveform deviation from a squarewave template
was not more than the deviation in normoxia. This indicates that peak flows in
hypoxia occurred early in inspiration rather than late. This can be seen also
in Figs. 4,
5,
6. Similarly, in hypoxia, peak
expiratory flow, although generally more constant, tended to occur at the end
of expiration. The exception to this was seen in REM sleep when peak
expiratory flows occurred at the onset of expiration, just as in normoxia
(Fig. 6). Peak flow rates in
inspiration and expiration were greater in hypoxia than in normoxia (Figs.
4,
5,
6).
Diaphragmatic activity during hyperventilation. Diaphragmatic
activity was examined in four cats. Diaphragmatic activity increased in
response to hypoxia, and the augmenting profile of diaphragmatic activity seen
in normoxia was unchanged (Figs.
4,
5,
6). Quantitative analysis
revealed that diaphragmatic activity during inspiratory airflow was
significantly increased in all states (Fig.
9). During the first part of expiration (E1), PIIA was
significantly increased in all three states, although the increase was least
in REM sleep (Figs. 6 and
9). In late expiration (E2),
diaphragmatic activity was significantly increased in wakefulness and NREM
sleep (Figs. 6 and
9).
View larger version (19K):
[in this window]
[in a new window]
|
Fig. 9. Diaphragmatic activity during normoxia and hypocapnic hypoxia. Data are
from 4 cats. Number of breaths analyzed: Wakefulness 21% O2 (308),
10% O2 (378); NREM 21% O2 (431), 10% O2
(696); REM 21% O2 (773), 10% O2 (539). Values are means
± SE. I, inspiration; E1, first half of expiration; E2, second half of
expiration. *Significance (P < 0.05), paired
t-test.
|
|
Periodic breathing. Periodic breathing in response to hypoxia was
infrequent and of short duration (<2 min) and did not occur in all
sessions. However, periodic breathing commonly occurred when cats returned to
breathing room air after exposure to hypoxia
(Fig. 10).
|
DISCUSSION
|
|---|
Breathing significantly increased in response to hypoxia in both sleep and
wakefulness. The increase in breathing was a true hyperventilation with a
sustained reduction in end-tidal CO2. This hyperventilation was
associated with significant changes in both the airflow waveform and
diaphragmatic activity. Sustained periodic breathing occurred infrequently in
hypoxia but was commonly seen as a posthypoxic response.
Augmentation vs. depression. Ventilation increases in response to
hypoxia (9,
16,
20). However, recent work in
awake cats and humans shows that a depression of ventilation occurs
secondarily if exposure to hypoxia is prolonged
(27,
28). This depression has
received considerable attention, especially from those interested in the
effects of hypoxia on the central nervous system
(3). However, the conditions
necessary for the occurrence of the depression are not known. Nor is it known
whether this depression occurs because of peripheral or central mechanisms.
Robbins (21) has suggested
that different mechanisms may be responsible for the depression of ventilation
under different conditions (e.g., peripheral mechanisms in awake animals and
central mechanisms in anesthetized preparations). Our data showed only
augmentation of ventilation during hypoxia. We do not know why we did not see
a secondary depression.
Chemosensitivity and breathing during sleep. The ventilatory
response to progressive hypoxia during NREM sleep is generally assumed to be
less than that during wakefulness. In REM sleep, ventilation in response to
hypoxia has been reported to be either decreased or not significantly
different compared with NREM sleep
(2,
6–8,
12,
18). Breathing irregularities
observed in REM sleep reportedly persist in hypoxia
(2,
18). In our study,
E was significantly increased and
end-tidal CO2 was significantly decreased in hypoxia in all states,
and state-specific patterns persisted. Thus, in REM sleep compared with NREM
sleep, VT values were lower, frequencies were higher, and end-tidal
CO2 levels were lower in hypoxia, just as they were in normoxia.
These results do not support claims of impaired chemosensitivity to oxygen in
sleep.
Airflow waveform and diaphragmatic activity. There were major
changes in the airflow waveform in hypoxia. The inspiratory pattern consisted
of a generally square waveform with peak flows at the onset of the phase,
which is the opposite of that seen in normoxia. The expiratory pattern was
also reversed from the normoxic pattern, with peak airflows at the end of
expiration rather than the beginning of that phase. This was true of
expiration in wakefulness and NREM sleep, but not REM sleep, in which
expiratory flows were maximal at the onset of expiration. Similar changes in
airflow waveforms have been reported during exercise and in response to
changes in dead space and airway resistance
(10,
11,
13,
19). Hypoxia causes an
increase in airway resistance, but the ventilatory response to hypocapnic
hypoxia apparently overrides the constricting effect of low O2
(25).
Changes in the pattern of diaphragmatic activity could also cause changes
in airflow waveforms. We found that in hypoxia diaphragmatic activity began
early during expiratory airflow, had a rapid rate of rise, and was increased
during inspiration and early expiration, which confirms the work of others
(4,
5,
15,
23,
24). The increased rate of
rise of diaphragmatic activity beginning during expiratory airflow could cause
the early peak in inspiratory airflow rates. Augmenting and intense
diaphragmatic activity could produce a constant airflow inspiratory waveform,
particularly if breathing is occurring at higher lung volumes
(5,
24). In expiration, increased
PIIA could slow expiratory airflow in early expiration, and the absence of
this braking activity in late expiration, perhaps in association with active
expiratory efforts, could allow greater flows at that time
(5,
26). Together, these events
could produce an expiratory airflow waveform that tends to be square with peak
flows at end expiration. In REM sleep, when PIIA is least, TE is
decreased, the expiratory waveform is correspondingly less square, and peak
expiratory airflow occurs during early expiration.
Airflow waveforms have been the subject of modeling and experimental
studies that have demonstrated that square inspiratory waveforms and waveforms
with peak flows in early inspiration require less work for achieving a given
alveolar ventilation than sinusoidal waveforms
(11,
29). Furthermore, square
waveforms during active expiration and waveforms with peak flows in early
expiration during passive expiration are mechanically more economical than the
corresponding sinusoidal wave
(29). Similarly, an increased
end-expiratory lung volume may conserve oxygen stores in hypoxia, and braking
of expiratory airflow as the result of increased PIIA may allow more time for
gas exchange (24,
29). Thus it may be that the
airflow waveforms that we observed in hypoxia require less mechanical work
than the waveforms seen during normoxia. However, we have no data to support
or refute this idea.
|
APPENDIX
|
|---|
Quantitative Characterization of the Airflow Waveform
Changes in airflow waveform were measured by using four numerical factors,
,
,
, and
. They measure deviation
(Fig. 11, A and
B) of an actual airflow waveform from Z- and
-templates. The latter represent, respectively, the triangular waveform
template and the square waveform template respiratory patterns.
Mathematically, the factors are defined by the equations
where f(t) is the airflow, TI and TE
are duration of inspiration and expiration, and VI and
VE are tidal volumes of inspiratory and expiratory waves, i.e.
The values of these factors are bound to the interval from 0 to 2. For a given
breath, the values of the factors are not independent
(Fig. 11C).
|
DISCLOSURES
|
|---|
Support was provided by National Heart, Lung, and Blood Institute Grants
HL-21257 (to J. M. Orem) and HL-62589 (to E. H. Vidruk and J. M. Orem), U. S.
Department of Education Graduate Assistance in Areas of National Need
Fellowship P200A80102 (to A. T. Lovering), Achievement Rewards for College
Scientists Foundation (to A. T. Lovering), and a Seed Grant from Texas Tech
University Health Sciences Center (to W. L. Dunin-Barkowski and J. M.
Orem).
|
ACKNOWLEDGMENTS
|
|---|
We acknowledge Thomas E. Dick, Cynthia A. Jumper, James S. Williams, and
Becky Tilton for critical review of this manuscript. Becky Tilton provided
animal care. Pradeep Dinakar assisted in some recordings.
|
FOOTNOTES
|
|---|
Address for reprint requests and other correspondence: J. M. Orem, Texas Tech
Univ. School of Medicine, Dept. of Physiology, Lubbock, TX 79430-6551 (E-mail:
john.orem{at}ttuhsc.edu).
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.
|
REFERENCES
|
|---|
- Andronikou S,
Shirahata M, Mokashi A, and Lahiri S. Carotid body chemoreceptor and
ventilatory responses to sustained hypoxia and hypercapnia in the cat.
Respir Physiol 72:
361-374, 1988.
- Berthon-Jones M and Sullivan CE. Ventilatory and arousal responses to hypoxia in sleeping
humans. Am Rev Respir Dis 125:
632-639, 1982.
- Bisgard GE and
Neubauer JA. Peripheral and central effects of hypoxia. In:
Regulation of Breathing, edited by Dempsey JA and Pack
AI. New York: Dekker, 1995, p.
617-668.
- Bonora M, Boule
M, and Gautier H. Diaphragmatic and ventilatory responses to alveolar
hypoxia and hypercapnia in conscious kittens. J Appl
Physiol 72:
203-210, 1992.
- Bonora M and
Vizek M. Changes in end-expiratory lung volume and diaphragmatic activity
during hypoxia and hypercapnia in cats. J Appl Physiol
79: 1900-1907,
1995.
- Bowes G,
Townsend ER, Kozar LF, Bromley SM, and Phillipson EA. Effect of carotid
body denervation on arousal response to hypoxia in sleeping dogs. J
Appl Physiol 51:
40-45, 1981.
- Bowes G, Woolf
GM, Sullivan CE, and Phillipson EA. Effect of sleep fragmentation on
ventilatory and arousal responses of sleeping dogs to respiratory stimuli.
Am Rev Respir Dis 122:
899-908, 1980.
- Douglas NJ,
White DP, Weil JV, Pickett CK, Martin RJ, Hudgel DW, and Zwillich CW.
Hypoxic ventilatory response decreases during sleep in normal men.
Am Rev Respir Dis 125:
286-289, 1982.
- Dripps RD and
Comroe JH Jr. The effect of the inhalation of high and low oxygen
concentrations on respiration, pulse rate, ballistocardiogram and arterial
oxygen saturation (oximeter) of normal individuals. Am J
Physiol 149:
277-291, 1947.
- Eisele JH,
Wuyam B, Savourey G, Eterradossi J, Bittel JH, and Benchetrit G.
Individuality of breathing patterns during hypoxia and exercise. J
Appl Physiol 72:
2446-2453, 1992.
- Hämäläinen RP. Optimization of respiratory airflow. In:
Modeling and Control of Breathing, edited by Whipp BJ
and Wiberg DM. New York: Elsevier, 1983, p.
181-188.
- Hedemark LL and
Kronenberg RS. Ventilatory and heart rate responses to hypoxia and
hypercapnia during sleep in adults. J Appl Physiol
53: 307-312,
1982.
- Lafortuna CL,
Minetti AE, and Mognoni P. Inspiratory flow pattern in humans.
J Appl Physiol 57:
1111-1119, 1984.
- Long WQ,
Giesbrecht GG, and Anthonisen NR. Ventilatory response to moderate hypoxia
in awake chemodenervated cats. J Appl Physiol
74: 805-810,
1993.
- Megirian D,
Ryan AT, and Sherrey JH. An electrophysiological analysis of sleep and
respiration of rats breathing different gas mixtures: diaphragmatic muscle
function. Electroencephalogr Clin Neurophysiol
50: 303-313,
1980.
- Nielsen M and
Smith H. Studies on the regulation of respiration in acute hypoxia.
Acta Physiol Scand 24:
293-305, 1951.
- Orem J, Netick
A, and Dement WC. Breathing during sleep and wakefulness in the cat.
Respir Physiol 30:
265-289, 1977.
- Phillipson EA,
Sullivan CE, Read DJ, Murphy E, and Kozar LF. Ventilatory and waking
responses to hypoxia in sleeping dogs. J Appl Physiol
44: 512-520,
1978.
- Proctor DF and
Hardy JF. Studies of respiratory airflow. 1. Significance of the normal
pneumotachogram. Bull Johns Hopkins Hosp
85: 253-280,
1949.
- Rahn H and Otis
AB. Alveolar air during simulated flights to high altitudes. Am
J Physiol 150:
202-221, 1947.
- Robbins PA.
Hypoxic ventilatory decline: site of action. J Appl
Physiol 79:
373-374, 1995.
- Schwieler GH. Respiratory regulation during postnatal
development in cats and rabbits and some of its morphological substrate.
Acta Physiol Scand Suppl 304:
1-123, 1968.
- Sherrey JH,
Pollard MJ, and Megirian D. Proprioceptive, chemoreceptive and sleep state
modulation of expiratory muscle activity in the rat. Exp
Neurol 101:
50-62, 1988.
- Smith CA,
Ainsworth DM, Henderson KS, and Dempsey JA. Differential timing of
respiratory muscles in response to chemical stimuli in awake dogs.
J Appl Physiol 66:
392-399, 1989.
- Sorkness RL and
Vidruk EH. Ventilatory responses to hypoxia nullify hypoxic tracheal
constriction in awake dogs. Respir Physiol
66: 41-52,
1986.
- Van der Ent CK,
van der Grinten CP, Meessen NE, Luijendijk SC, Mulder PG, and Bogaard JM.
Time to peak tidal expiratory flow and the neuromuscular control of
expiration. Eur Respir J 12:
646-652, 1998.
- Vizek M,
Pickett CK, and Weil JV. Biphasic ventilatory response of adult cats to
sustained hypoxia has central origin. J Appl Physiol
63: 1658-1664,
1987.
- Weil JV and
Zwillich CW. Assessment of ventilatory response to hypoxia: methods and
interpretation. Chest 70:
124-128, 1976.
- Yamashiro SM and Grodins FS. Optimal regulation of respiratory airflow. J
Appl Physiol 30:
597-602, 1971.
This article has been cited by other articles:
|
|
|
|
 
G. Taccola, L. Secchia, and K. Ballanyi
Anoxic persistence of lumbar respiratory bursts and block of lumbar locomotion in newborn rat brainstem spinal cords
J. Physiol.,
December 1, 2007;
585(2):
507 - 524.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. T. Lovering, J. J. Fraigne, W. L. Dunin-Barkowski, E. H. Vidruk, and J. M. Orem
Medullary Respiratory Neural Activity During Hypoxia in NREM and REM Sleep in the Cat
J Neurophysiol,
February 1, 2006;
95(2):
803 - 810.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2003 by the American Physiological Society.
TOP
ABSTRACT
MATERIALS AND METHODS
