Vol. 85, Issue 2, 490-496, August 1998
Transient respiratory augmentation elicited by acute head-down
tilt in the anesthetized cat
Fadi
Xu,
Zhong
Zhang, and
Donald T.
Frazier
Department of Physiology, University of Kentucky, Lexington,
Kentucky 40536
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ABSTRACT |
Acute head-down
tilt (AHDT, 
30°) in humans induces a transient ventilatory
augmentation for 1-2 min accompanied by a high venous return.
However, the mechanisms underlying this respiratory response remain
obscure because of limitations of experiments carried out in human
subjects. The present study was undertaken to determine whether
AHDT-induced respiratory augmentation exists in the anesthetized,
paralyzed, and ventilated cat and, if so, whether this response depends
on 1) the cerebellum,
2) the carotid sinus (CS)
and/or vagal afferents, and
3) elevation of central venous
return. The integrated phrenic neurogram, arterial blood pressure,
central venous pressure (CVP), and end-tidal
PCO2 were recorded before, during,
and after AHDT. The results showed that AHDT produced a transient (~2
min) enhancement of minute phrenic activity (~30%) primarily via an
increase in peak integrated phrenic neurogram amplitude associated with
a remarkable elevation of CVP (~3 min). Cerebellectomy, CS
denervation, bilateral vagotomy, or clamping CVP did not affect the
presence of the AHDT-induced minute phrenic activity response. These
findings demonstrate that the anesthetized cat is a suitable model for
investigating the mechanisms involved in AHDT-induced respiratory
augmentation. Preliminary studies suggest that this response does not
require the cerebellum, CS/vagal afferents, or an associated rise in
central venous return.
cerebellectomy; vagotomy; carotid body denervation; central venous
pressure; phrenic efferent activity; vestibular system
| |
INTRODUCTION |
ACUTE HEAD-DOWN TILT (AHDT, 30°) has been
used to investigate mechanisms underlying the respiratory responses to
microgravity or exercise in humans. Relevant studies indicated that
AHDT transiently increased minute ventilation within 1-2 min in
association with an elevation of venous return (12, 14, 15, 21).
Insight into the underlying mechanisms remains somewhat vague, since in human subjects it is difficult to design experiments that separate potential central integrating sites and peripheral afferents
responsible for AHDT-induced respiratory augmentation.
Several lines of evidence suggest a possible cerebellar contribution to
the AHDT-induced respiratory augmentation. First, recent experiments
have demonstrated cerebellar involvement in increased respiratory
response to stress. Respiratory responses to hypoxia (29) and
hypercapnia (23, 28) were profoundly attenuated after whole or partial
ablation of the cerebellum. Conversely, elevation of respiratory
amplitude and/or frequency was elicited by electrical
stimulation of given sites within the cerebellar fastigial nucleus (26,
27). Second, the ventilatory response to mechanical stimulation of the
gastrocnemius muscle was significantly reduced after ablation of the
anterior lobe of the cerebellum (19). In addition, the respiratory
response to activation of respiratory muscles of spontaneously
breathing cats was also altered by cerebellectomy (4, 30). These
results demonstrated that the cerebellum was significantly involved in the respiratory response to alteration of skeletal muscle tone. Third,
the cerebellar role in modulation of spinal cord and brain stem
mechanisms involved in postural control has been well established (8).
The possible contribution of the associated elevation of venous return
during AHDT to the respiratory augmentation has been previously
considered. Studies have shown that high central venous return can
augment respiration by stimulating right ventricular mechanoreceptors
via elevation of filling pressure (9, 13) or carotid/pulmonary
CO2 chemoreceptors (11, 20, 24,
25) through increasing CO2 flow
(product of CO2 concentration and blood flow). It was postulated that the respiratory augmentation during
AHDT was the result of increased venous return that subsequently activated chemo- and/or mechanoreceptors [carotid sinus
(CS) and vagus nerves]. Direct evidence to support this
assumption, however, has not been presented.
The major goal of our study was to determine whether AHDT causes
transient respiratory augmentation in the anesthetized cat. If so,
potential contributors such as the cerebellum, the carotid or pulmonary
chemoreceptors, and an increased central venous return will be
investigated. The experiments were conducted in anesthetized, paralyzed, and artificially ventilated cats. Phrenic efferent activity,
as an index of respiratory motor drive, was recorded with and without
AHDT (30°) challenge. We found that AHDT produced a
transient augmentation in phrenic efferent activity (for ~2 min) as
well as an elevation of central venous pressure (CVP) similar to that
observed in humans. We also found that the phrenic responses to AHDT
persisted after cerebellectomy, CS denervation, vagotomy, or CVP
clamping (maintaining CVP at its control level during AHDT). These
results establish that the anesthetized cat is a suitable model to
study the mechanisms underlying the AHDT-induced respiratory
augmentation. The preliminary experiments presented here were designed
to investigate potential contributors, and they reveal that neither the
cerebellum nor the high CVP (activation of CS and/or vagal
afferents) is essential to the occurrence of this respiratory
augmentation.
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METHODS |
Experiments were performed on 13 adult cats (2.5-3.9 kg) of
either sex. To limit brain edema resulting from craniotomy and cerebellectomy, dexamethasone (4 mg) was injected 1 day before and on
the day of the experiment (2 mg). Anesthesia was initiated in the cat
with thiopental sodium (50 mg/kg) and maintained with 
-chloralose
(40 mg/kg). Supplemental anesthesia was administered as signaled by
marked fluctuation in heart rate/arterial pressure and/or
presence of eye-blink reflexes. Rectal temperature was monitored
continuously (model 73ATA, Yellow Springs Instruments) and
maintained at ~38°C via a heating pad and a radiant heat lamp.
General surgeries.
The left femoral vein and artery were cannulated. The former was
utilized for anesthetic supplement and the latter for monitoring arterial blood pressure (ABP; model P23AA, Statham) and periodic analysis of arterial blood gases (model 1306 pH/blood-gas analyzer, Instrumentation Laboratory). Acidosis, if present, was corrected by
addition of bicarbonate (75 mg/ml iv) before the experimental protocols
were performed.
Animals were tracheotomized and subsequently paralyzed with
gallamine triethiodide (4 mg/kg for induction followed by continuous supplementation with 4 mg · kg
1 · h1)
and artificially ventilated. Expiratory end-tidal
PCO2 and
PO2
(PETCO2 and
PETO2, respectively) were
monitored (model 78356A, Hewlett-Packard). The volume and rate of the
ventilator were adjusted at an appropriate level for maintaining
PETCO2 at ~30 Torr and
kept constant in each animal throughout the experiment. The level of
PETO2 was maintained at
slightly >100 Torr by addition of
O2 into the inhaled gas throughout
the experiment. After paralysis, supplemental anesthesia was
administered as needed whenever abnormal irregularities in elevation of
arterial pressure, heart rate, and respiratory rate and pattern were
observed.
The cervical segments of both common carotid arteries were
isolated via a midline surgical incision and looped with umbilical tape
for reduction of hemorrhage by transient occlusion during cerebellectomy. The cervical vagus nerves were carefully isolated and
wrapped loosely with a loop of suture for later bilateral transection.
Animals were placed prone in a Kopf head and stereotaxic apparatus
mounted on a stage. The level of the stage was adjustable to produce
whole body AHDT. A dorsal occipital craniotomy was performed, the dura
was reflected, and the exposed surface was covered with mineral oil.
Phrenic neurogram (PN) recording.
The right C5 cervical
phrenic nerve rootlet was isolated via a dorsal approach and cut. The
central end of the nerve was mounted on a bipolar recording electrode
and covered with petroleum jelly to prevent drying and to protect the
nerve contact with the electrode. Raw signals of the PN were filtered
(300-3,000 Hz) and amplified using a preamplifier (model P15,
Grass Instruments) before display on a storage oscilloscope (model
5103n, Tektronix). The amplified signals were in turn processed by an
integrator with a 100-ms time constant (moving average, model
MA-821RSP, Charles Woel Enterprises) to obtain integrated PN
(
PN).
CVP recording.
The left cervical external jugular vein was isolated, and a catheter
(~1.5-mm diameter) was advanced close to the right atrium by
measuring the distance from the heart (felt from heartbeat) to the
cannulating site before insertion. The proximal end of the catheter was
attached to a three-way switching device that allowed the catheter to
be connected to 1) a pressure
transducer (model P23BB, Statham) connected to a polygraphic recorder
to monitor CVP and 2) a syringe (10 ml) that served as a reservoir (see below).
Protocol.
After baseline cardiorespiratory variables became stable, AHDT was
performed by adjusting the head holder to a 30° position for
a fixed time period. Initially, the duration of AHDT was ~5 min. When
the transient respiratory augmentation was confirmed to occur ~2 min
after the onset of AHDT (see
RESULTS), the AHDT duration was
shortened to 2-3 min. To minimize the mechanical fluctuation
produced by the sudden change in posture, a period of ~15 s was taken
to gradually position the head to the given head-down tilt. The
recording electrodes were affixed to the stereotaxic apparatus to
maintain a constant contact between the phrenic nerve and the recording
electrode during AHDT.
AHDT was carried out in eight animals, and the same protocol was
repeated in six of the animals after cerebellectomy. Cerebellectomy was
performed by transection of the cerebellar peduncles with a blunt
spatula followed by aspiration of cerebellar tissue. Bleeding was
carefully controlled during cerebellectomy with transient compression
of the carotid arteries (detailed in Ref. 30). The exposed cut surface
was gently packed with absorbable hemostatic agent (Surgicel) and
covered with mineral oil. Bilateral vagotomy was subsequently carried
out in four cats, and the AHDT was repeated.
The AHDT protocol was also conducted in five other cats in which the CS
nerves were transectioned (CS denervation). CS nerves were carefully
isolated using a ventral approach and confirmed by tracing their origin
to the glossopharyngeal nerve. Transection dramatically blunted the
respiratory response to inhalation of six breaths of pure
N2. AHDT was subsequently repeated
when CVP was clamped at its control level by allowing blood volume that shifts, as a result of AHDT, into a syringe attached to the left jugular vein catheter. The blood in the reservoir was slowly (2 min)
injected back into the femoral vein after AHDT. Bilateral vagotomy was
subsequently performed in three of the five cats, and AHDT was
repeated.
During the experiment the raw PN, PN, ABP, CVP,
and PETCO2 were continuously
monitored and recorded on a polygraph (model 7D, Grass) for later data
analysis. One hour was generally allowed after completion of each
surgical procedure before control values were recorded.
Data analysis.
The respiratory variables include the peak value of
PN
(PNpeak),
respiratory frequency (f), minute phrenic activity (MPN, product of
PNpeak and
f), PETCO2, mean ABP (MABP),
and CVP. They were collected and averaged from the 0.5-min period
immediately before the onset (control) of AHDT and the 0.5-min period
during the AHDT that displayed the maximal response
(PNpeak). Respiratory responses
(PNpeak, f,
and MPN) to AHDT were presented as percent change from control.
Baseline (control) cardiorespiratory variables and the changes in MABP, PETCO2, and CVP during AHDT
were expressed as absolute values. Values are means ± SE. The
significant differences of cardiorespiratory responses to AHDT vs.
control and among various preparations were examined by utilizing
one-way ANOVA with Student-Newman-Keuls test. A one-way
repeated-measures ANOVA with post hoc test was used in the protocols
where AHDT was repeated after different experimental treatments (e.g.,
cerebellectomy and vagotomy). P < 0.05 was used to determine significance.
| |
RESULTS |
Respiratory responses to AHDT in intact cats.
In anesthetized, paralyzed, and artificially ventilated cats, phrenic
efferent responses to AHDT were generally similar to the ventilatory
responses observed in humans (12, 14, 15, 21). They were characterized
as a brief (~2 min), significant enhancement of
PNpeak with
little change in f. A typical example is shown in Fig.
1, in which the cat was exposed to AHDT for
4 min. Approximately 10 s after initiation of AHDT, CVP displayed a
smooth increase (from ~1 cmH2O)
and reached a plateau (~6 cmH2O)
~2 min after the onset of AHDT. CVP returned to control values within
1 min after withdrawal of AHDT. A progressive augmentation of
PNpeak began
~20 s after the onset of AHDT and reached a maximum within 2 min.
Thereafter, it started to decline, even though CVP remained at plateau.
PNpeak gradually returned to its control level ~1 min after the offset of
AHDT. MABP showed no pronounced change in response to AHDT. Group data
for the respiratory responses in the intact cat are presented in Fig.
2. Compared with control,
PNpeak and
MPN were significantly enhanced to 21.2 ± 6.1 and 28.6 ± 6.0% during AHDT with little change in f (5.5 ± 3.8%). These
respiratory alterations
(PNpeak and
MPN) returned to control values within 1 min after termination of AHDT
(3.9 ± 3.3 and 4.3 ± 8.7%, P > 0.05).
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Fig. 1.
Respiratory responses to acute head-down tilt (AHDT) in an
anesthetized, paralyzed, and artificially ventilated cat. ABP, arterial
blood pressure; PN, integrated phrenic neurogram;
CVP, central venous pressure. Horizontal bars, markers for onset and
offset of AHDT.
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Fig. 2.
Comparison of AHDT-induced respiratory augmentation in intact
(crosshatched bars, n = 8) and
decerebrate cats (filled bars, n = 6). Control
levels (0%) for peak value of PN
(PNpeak),
respiratory frequency (f), and minute phrenic activity (MPN) are
not shown. Values are means ± SE.
* P < 0.05, control (0%,
without tilt) vs. tilt.
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Cerebellar role in AHDT-induced respiratory response.
Cerebellectomy did not significantly alter baseline respiratory
variables (Table 1). Similarly, as shown in
Fig. 2, the patterns of respiratory responses
(PNpeak,
f, and MPN) to AHDT were not significantly different from those
obtained after removal of the cerebellum. Compared with the intact
preparation, the slight decreases in
PNpeak and
MPN after cerebellectomy were not statistically significant. These results suggest that the integrity of the cerebellum is not critical for the AHDT-induced respiratory augmentation.
Effect of CS denervation on AHDT-induced respiratory response.
CS denervation did not significantly affect baseline respiratory
variables (Table 1). A typical example of respiratory responses to AHDT
in a CS-denervated cat is shown in Fig.
3A. The
basic characteristics of the respiratory responses to AHDT were similar to those observed in the intact preparation, i.e., a remarkable elevation of
PNpeak
without an apparent change in f. Interestingly, group data (Fig.
4) revealed that the amplitude of
respiratory augmentation was greater in the CS-denervated than in the
intact preparations. The observation that CS denervation increased
rather than decreased the respiratory response to AHDT was contrary to
our hypothesis and those of other investigators. These data suggest an
inhibitory effect of CS nerves on the AHDT-induced respiratory
response.
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Fig. 3.
Typical respiratory responses to AHDT in a carotid sinus-denervated cat
before (A) and during central venous
pressure (CVP) clamp (B).
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Fig. 4.
Effect of carotid sinus denervation on AHDT-induced respiratory
augmentation. Crosshatched bars, intact cats
(n = 8); filled bars, carotid
sinus-denervated cats (n = 5). Control
levels (0%) for
PNpeak, f,
and MPN are not shown. Values are means ± SE.
* P < 0.05, control (0%,
without tilt) vs. tilt.  Significantly different from intact
(P < 0.05).
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AHDT-induced respiratory response during CVP clamping.
An experimental recording that illustrates the effect of CVP on
respiratory responses to AHDT is depicted in Fig. 3. Compared with
control (Fig. 3A), the respiratory
responses were not profoundly altered when the CVP was clamped at its
control value during AHDT (Fig. 3B).
Group data of the respiratory responses to AHDT with and without the
CVP clamped are displayed in Fig. 5. As
shown in Fig. 5A, AHDT increased CVP
from ~1.5 cmH2O (control) to
~6 cmH2O. When the CVP was
clamped during AHDT, its values were very close to the control;
however, respiratory excitatory responses (PNpeak and
MPN) persisted (Fig. 5B). Moreover,
none of the respiratory responses to AHDT were markedly different
between the preparations with and without CVP clamped.
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Fig. 5.
Comparison of AHDT-induced CVP (A)
and respiratory responses (B) with
(CVP-C, crosshatched bars) and without CVP clamped (CVP-C, filled
bars). Open bars, baseline (before AHDT). Control levels
(0%) for
PNpeak, f,
and MPN are not shown in B. Values are
means ± SE. * P < 0.05, control (Ctrl, without tilt) vs. tilt
(n = 5).
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AHDT-induced respiratory response in vagotomized cats.
In seven cats, bilateral vagotomy was carried out after cerebellectomy
(n = 4) or CS denervation
(n = 3). After bilateral vagotomy,
there was an increase in
PNpeak and a
decrease in f, leading to an insignificant change in MPN (Table 1). As
shown in Fig. 6, the respiratory
augmentation in response to AHDT was not eliminated after vagotomy.
These findings suggest that AHDT-induced respiratory augmentation is
independent of vagal afferents.
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Fig. 6.
Comparison of AHDT-induced respiratory augmentation before
(crosshatched bars) and after vagotomy (filled bars). Values are
means ± SE (n = 7).
* P < 0.05, control (0%,
without tilt) vs. tilt.
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Comparison of MABP and
PETCO2 response to
AHDT in different preparations.
Table 2 lists the responses of MABP and
PETCO2 to AHDT in the
intact, cerebellectomized, CS-denervated, vagotomized, and CVP-clamped
preparations. There was a slight tendency to increase MABP and
PETCO2 during AHDT in the
different experimental preparations tested; however, these changes
were not significant.
| |
DISCUSSION |
AHDT-induced respiratory augmentation in anesthetized cats.
One of the major findings in the present study is that AHDT can produce
a transient increase in MPN associated with an elevation of CVP in
anesthetized cats. This augmented response was a reproducible phenomenon and was elicited ~20 s after the onset of the AHDT. It is
characterized by a remarkable enhancement of
PNpeak (~30%) with little change in f. These results are consistent with previous studies on humans in whom AHDT caused a transient ventilatory augmentation within 1-2 min (12, 14, 15, 21) via an increase in
tidal volume (14, 15) or f (12, 15). The ventilatory response increased
25-38% compared with control (15, 21) with a latency of ~15 s
(21). In humans, there was a 200-ml blood volume shift from the
peripheral to the pulmonary circulatory system (14), with an elevation
of the jugular venous pressure from 8 to 22 cmH2O (10) when the subjects were
tilted from 0 to 30°. In cats subjected to the same level of
AHDT, the CVP responded in a very similar manner (increasing from 1.5 to 6 cmH2O). The head-down tilt
maneuver was conducted from the prone position in the cat, whereas in
human subjects the tilt has been generally applied from the supine
position (12, 15, 21). However, the similarities of the basic
cardiorespiratory responses described above suggest that application of
the same degree of AHDT in different positions did not substantially
affect cardiorespiratory responses. These comparative findings
established the feasibility of utilizing the anesthetized cat model to
explore respiratory-related peripheral afferents and central nervous
system sites that are critical to the AHDT-induced respiratory
augmentation.
As mentioned earlier, some studies on humans infer that ventilatory
augmentation during AHDT is due to an elevation of CVP that results in
a concomitant high CO2
flow. The lack of change in
PETCO2 or alveolar
PCO2 in humans during AHDT has been
explained as a result of simultaneous hyperventilation, since
CO2 was significantly increased
(21). To test this assumption, paralyzed cats were used in our
experiments. We reasoned that if AHDT produced high
CO2 flow through the lungs, as
supposed in humans, using the artificially ventilated animal
preparation (without hyperventilation) should reveal an increase in
PETCO2 during the period of
AHDT. We did observe that
PETCO2 did not increase
significantly during AHDT, implying a negligible increase in
CO2 flow in the animal
preparation. One could argue that the
PETCO2 did not significantly
increase during AHDT as a result of the animals' lower metabolism
under anesthesia. However, it is clear that the respiratory
augmentation to AHDT observed in our experiments cannot be explained by
a high CO2 flow passing through
the lungs. In awake humans an increase in CO2 flow during AHDT has been
postulated. In contrast to the anesthetized and paralyzed cat, this
increase in CO2 flow is presumably
due to an increased muscle activity induced by posture change.
Phrenic efferent activity was recorded instead of airflow (minute
ventilation) so that the AHDT effect on respiratory motor drive could
be more directly ascertained. It has been reported that AHDT produces a
change of diaphragmatic length (as a result of the shift in the
abdominal contents) and tension (16) that could affect ventilation. The
fact that phrenic nerve efferent activity was increased in response to
AHDT strongly demonstrates that this respiratory augmentation requires
central nervous system integration and not just local changes in muscle
mechanics. In addition, employing the paralyzed preparation minimized
the possible variations of afferent inputs from skeletal muscles
activated in the spontaneously breathing cats during AHDT. The inputs,
for example, emanating from the diaphragm (4) and limb muscles (7),
have been demonstrated to modulate respiration. It would appear that
altering muscle afferent activity did not preclude the observed
AHDT-induced respiratory augmentation.
Cerebellar involvement.
Our observations that cerebellectomy failed to alter AHDT-induced
respiratory augmentation suggest that the cerebellum is not essential
for this respiratory response. This finding was somewhat surprising,
since removal of the cerebellum depresses respiratory augmentation in
response to stressed breathing (23, 28, 29), and the cerebellar role in
skeletal responses to changes in the muscle tone (posture) is well
known (8, 19). We cannot rule out the possibility that the absence of a
cerebellar effect during AHDT is due to the paralyzed preparation,
since the alterations in muscle tone induced by AHDT could be
profoundly diminished in the paralyzed preparation.
Role of carotid and intrapulmonary chemoreceptors.
Another major finding is that the occurrence of AHDT-induced
respiratory augmentation is independent of the influence of CS and
vagal afferents. These results cast doubt on the hypothesis that
AHDT-induced ventilatory augmentation depends on the activation of
carotid and intrapulmonary chemoreceptors. Previous studies have
indicated that an increase of CO2
flow passing through the carotid body (11, 20) and lungs (24, 25)
produces respiratory augmentation. Therefore, several investigators
(12, 21) postulated that AHDT-induced respiratory augmentation resulted
from increased CO2 flow (because
of high venous return) that stimulated carotid and intrapulmonary
chemoreceptors. Our data strongly argued against this assumption, since
AHDT-induced respiratory responses were not eliminated by transection
of carotid sinus and vagal nerves innervating carotid and
intrapulmonary chemoreceptors, respectively. In contrast, our
observation that the respiratory augmentation became greater in the
CS-denervated preparation implies an inhibitory effect of the CS nerve
on AHDT-induced respiratory augmentation.
The enhancement of respiratory augmentation during AHDT in
CS-denervated cats might result from the blockade of carotid
baroreceptor afferents. A significant, transient elevation of common
carotid arterial pressure was observed in humans within the first 2 min of AHDT (30°), and this response was not accompanied by
significant changes in systemic arterial pressure (14). The latter is
in agreement with our results that AHDT in anesthetized cats did not
alter MABP significantly. Activation of carotid baroreceptors is
reported to inhibit respiration in CS-intact cats but, conversely, increase ventilation in CS-denervated cats (17). In contrast, a
decrease in the carotid baroreceptor activity enhances respiration (3).
Thus one may logically propose that in CS-intact cats AHDT-induced
respiratory responses have been attenuated by increased blood pressure
in the common carotid artery because of microgravity induced by AHDT.
This assumption is consistent with our finding that AHDT-induced
respiratory responses became greater in CS-denervated cats as a result
of the absence of the inhibitory effects emanating from the carotid
baroreceptors.
The fact that the animals'
PETO2 was maintained at
slightly >100 Torr in the present study suggests that AHDT-induced respiratory augmentation does not depend on activation of
O2 chemoreceptors. In agreement
with this finding, Lawler et al. (12) also reported that inhalation of
95% O2 to blunt activity of the
carotid chemoreceptors produced no discernible change in the
ventilatory response to AHDT. Carotid denervation leads to an
attenuation of ventilation when cats are breathing room air (5, 18).
However, if an animal was exposed to hyperoxia, ventilation was
increased (18). In our study, animals were ventilated with gas mixtures
containing high O2 to maintain
PETO2 at just >100 Torr.
Therefore, it might explain the lack of pronounced changes in baseline
respiratory variables observed after CS denervation.
Contribution of mechanoreceptors in right heart.
A rise of right ventricular pressure is capable of stimulating
mechanoreceptors, subserved by vagal and/or sympathetic
afferents (1, 9, 13), that reflexly elevate minute ventilation. A
question has been raised as to whether AHDT-produced elevation in CVP
stimulates respiration via increased right ventricular pressure. Our
observations appear not to support this hypothesis. First, respiratory
responses to AHDT did not change markedly when CVP was clamped (Figs. 3
and 5). Second, bilateral vagotomy, which eliminates the major
mechanoreceptor inputs from the right heart, failed to alter the
respiratory responses to AHDT (Fig. 6). Third, AHDT-induced respiratory
augmentation fell toward its control value, even though the CVP
response remained at plateau (Fig. 1), demonstrating a dissociation
between the respiratory and CVP responses. Although no attempt was made
in our study to directly test the effects of sympathetic afferents from
the heart, our results appear not to support the notion that the
AHDT-induced ventilatory augmentation resulted from stimulation of
sympathetic afferents. First, we found that respiratory augmentation
persists during AHDT without an increase in CVP. Second, in the present study, no significant increase in ABP was observed. Considering these
results, we infer that mechanoreceptors (within the right ventricle)
activated by enhancing CVP are not important for eliciting AHDT-induced
respiratory augmentation in our experimental preparation.
Other possible factors.
Our experiments reported here have clarified that the cerebellum, CS
and vagal afferents, and CVP are not required for AHDT-induced respiratory augmentation in anesthetized cats. Although our data cannot
conclusively answer where the signals evoked by AHDT are sensed and
integrated, our speculation is that AHDT causes an increase in blood
flow and CO2 delivery to the brain
stem, resulting in enhanced stimulation of central chemoreceptors. In
humans, AHDT has been reported to elicit a striking transient elevation of blood flow (27%) (10). Our finding that AHDT-induced respiratory responses persisted in CS-denervated cats does not rule out the possibility that increased CO2
flow within the brain stem excites central chemoreceptors to stimulate
respiration. Another possibility would be an involvement of the
vestibular system in this respiratory response to AHDT. Anatomically,
bulbospinal neurons projecting to phrenic motoneurons have been
identified in the medial and lateral vestibular nuclei (2). In
decerebrate cats, electrical or chemical (microinjection of glutamate)
stimulation of the vestibular nucleus dramatically enhanced the
PNpeak activity (6), indicating that activation of cell bodies residing in the
vestibular system has an excitatory effect on respiration. Functional
activation of the vestibular system by rotating the head in
CS-denervated, vagotomized, and decerebrate cats significantly altered
respiration (22). Therefore, the vestibular system may well be involved
in the respiratory augmentation during AHDT.
Summary.
AHDT-induced cardiorespiratory responses in anesthetized cats are
basically similar to those in humans, including
1) a transient respiratory
augmentation (~2 min) associated with an elevation in CVP and
2) no significant change in MABP.
These findings demonstrate that the anesthetized cat is a suitable
model for investigating the mechanisms involved in AHDT-induced
respiratory augmentation. Preliminary studies suggest that the
respiratory responses to AHDT are not triggered by the integrity of the
cerebellum, CS and vagal nerves, and enhancement of CVP.
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ACKNOWLEDGEMENTS |
The authors thank members of the University of Kentucky respiratory
group for helpful critiques and Donna Painter and Mandy Frank for
assistance in data collection.
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FOOTNOTES |
This study was supported by National Heart, Lung, and Blood Institute
Grant HL-40369.
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 reprint requests to F. Xu.
Received 12 February 1998; accepted in final form 13 April 1998.
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Abstract
Introduction
