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The John Rankin Laboratory of Pulmonary Medicine, University of Wisconsin School of Medicine, Madison, Wisconsin 53705
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We assessed the time course of changes in eupneic arterial PCO2 (PaCO2) and the ventilatory response to hyperoxic rebreathing after removal of the carotid bodies (CBX) in awake female dogs. Elimination of the ventilatory response to bolus intravenous injections of NaCN was used to confirm CBX status on each day of data collection. Relative to eupneic control (PaCO2 = 40 ± 3 Torr), all seven dogs hypoventilated after CBX, reaching a maximum PaCO2 of 53 ± 6 Torr by day 3 post-CBX. There was no significant recovery of eupneic PaCO2 over the ensuing 18 days. Relative to control, the hyperoxic CO2 ventilatory (change in inspired minute ventilation/change in end-tidal PCO2) and tidal volume (change in tidal volume/ change in end-tidal PCO2) response slopes were decreased 40 ± 15 and 35 ± 20% by day 2 post-CBX. There was no recovery in the ventilatory or tidal volume response slopes to hyperoxic hypercapnia over the ensuing 19 days. We conclude that 1) the carotid bodies contribute ~40% of the eupneic drive to breathe and the ventilatory response to hyperoxic hypercapnia and 2) there is no recovery in the eupneic drive to breathe or the ventilatory response to hyperoxic hypercapnia after removal of the carotid chemoreceptors, indicating a lack of central or aortic chemoreceptor plasticity in the adult dog after CBX.
chemoreception; ventilatory control; compensation; rebreathing
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THE RELATIVE CONTRIBUTION of the central and peripheral chemoreceptors to the ventilatory response to CO2 has long been debated. A portion of the confusion may be related to the assumption that hyperoxia completely eliminates peripheral CO2 responsiveness (2, 7, 9, 20). This assumption does not seem to be consistent with carotid sinus nerve recording studies (11, 12, 17) that show that hyperoxia reduces, but does not eliminate, carotid body chemoreceptor sensitivity to CO2.
Differences in methodology may also account for some of the conflicting results obtained from studies attempting to partition the CO2 response into central and peripheral components. Some investigations using isolated pontomedullary perfusion in the anesthetized cat (13) attributed almost half of the hypercapnic ventilatory response to the carotid chemoreceptors, whereas studies in the same species by others using discrete brain stem lesioning attributed virtually all of the CO2 response to central chemoreceptors (21, 30). Investigations using the carotid body denervation (CBX) model to partition the CO2 response into central and peripheral components have also come to differing conclusions, possibly because of the varying time points at which the animals were studied post-CBX. For example, studies in the anesthetized rabbit (15) immediately post-CBX have demonstrated that the carotid chemoreceptors do not contribute to the ventilatory response to CO2, whereas studies in the awake pony (3) and goat (24) days to weeks after denervation have shown profound decreases in ventilatory drive and CO2 responsiveness of the ventilatory control system that are time dependent.
The purpose of the present study was to determine the contribution of the carotid chemoreceptors to the eupneic drive to breathe and to the ventilatory response to hyperoxic hypercapnia in the awake dog and whether there is adaptation/compensation in the ventilatory control system after CBX. We attempted to avoid the assumptions and potential methodological limitations cited above. We found that the carotid bodies contribute significantly to the eupneic drive to breathe in normoxia and to the ventilatory response to CO2, even in the presence of hyperoxia. We found no evidence of central nervous system (CNS) or aortic chemoreceptor compensation with respect to ventilatory control for up to 3 wk post-CBX.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Animals
Nine female, mixed-breed dogs (20-25 kg) were trained to perform the experimental protocol and then studied repeatedly before and after surgical removal of the carotid bodies (CBX) or sham CBX. All dogs were studied while awake and not in estrus. The experimental and surgical protocols were approved by the Animal Care and Use Committee at the University of Wisconsin, Madison.Surgery
After the dogs were acclimatized to the laboratory and trained to perform the experimental protocol, they underwent the first of two aseptic surgical procedures under general anesthesia. The first surgery consisted of installing chronic catheters into the femoral artery and vein, as well as bipolar electromyogram (EMG) recording electrodes into the crural diaphragm. Animals were given analgesics and antibiotics as appropriate and recovered for 10 days before control data collection was begun. After control measurements were obtained, the second surgery consisted of either CBX or sham CBX. In either case, a 10-cm incision was made down the ventral midline of the neck and the carotid sinuses were located bilaterally. CBX consisted of stripping the adventitia from all of the arteries within ~2 cm of the sinuses, whereas sham CBX was accomplished by visually locating the sinuses bilaterally without disturbing the region.Ventilation and EMGs
Ventilation was measured using a tight-fitting muzzle mask connected to a heated pneumotachograph that was calibrated daily with four known flows. Crural diaphragm EMG signals were amplified, band-pass filtered, rectified, and moving-time averaged (100 ms time-constant; models BMA-931; MA-821RSP, CWE).Eupneic Blood Gases
Data collection began with determination of the dogs' arterial blood gases while they were eupneic and air breathing without a mask on. Blood-gas measurements were made in triplicate and analyzed on an automated gas analyzer (model ABL-505, Radiometer) validated daily with tonometered blood. The samples were corrected for both body temperature and systematic error revealed by tonometry data.Peripheral Chemoresponsiveness Tests
CBX was confirmed by elimination of the ventilatory response to intravenous bolus injections of NaCN (0.03-0.05 mg/kg). In each dog, five of these NaCN tests were performed on two separate occasions during control testing and on each day of data collection post-CBX. The ventilatory response to NaCN was quantified by expressing the average tidal volume (VT) during the 6- to 18-s period after the NaCN injection (6-s circulatory delay) as a percentage of the average VT during the 1-2 min before the injection. A ventilatory response to NaCN was considered significant for any given animal when the average VT during the postinjection period was greater than the average VT during the preinjection period plus two standard deviations.Elimination of the hyperventilatory response to steady-state hypoxia [arterial PO2 (PaO2) ~35 Torr] and reversal of the response to steady-state hyperoxia from a hypo- to a hyperventilation were also used as confirmatory measures of CBX. In each dog, these steady-state hypoxic and hyperoxic tests were performed on two to three separate occasions during each of the pre- and post-CBX testing periods.
Hyperoxic CO2 Response Test
A modified version of the Read rebreathe test (27) was used to assess the ventilatory response to hyperoxic hypercapnia. The test consisted of having the dogs rebreathe for 2-3 min from a 3-liter rebreathing bag that was initially filled with a CO2 concentration equal to the animal's eupneic PETCO2 for that day; the balance of the gas was O2. Inspired minute ventilation (
I) and its components were plotted on a
breath-by-breath basis against end-tidal PCO2
(PETCO2), and a linear regression was
calculated from all the points. Four to five of these tests
were performed on each of 2-4 control days and on each day
post-CBX in each dog. The slopes of the regression lines for each day
were averaged with the mean used as an index of the ventilatory
responsiveness to hyperoxic hypercapnia on that day.
Protocol
Measurements of eupneic arterial blood gases and ventilatory responses to intravenous injections of NaCN, steady-state hypoxia, hyperoxia, and hyperoxic CO2 rebreathing were obtained in each animal on multiple occasions before and after CBX or sham CBX.Measurement Reproducibility
Hyperoxic CO2 response tests were conducted over each of 2-4 days before CBX, with four to five trials per animal per day. We found that the slopes of the hyperoxic rebreathe ventilatory responses varied randomly within an animal as determined by repeat testing: 1) among the five trials conducted within a single test session (mean coefficient of variation = ± 20% in control testing and ± 26% post-CBX) and 2) between control days in the intact animal (mean coefficient of variation = ± 30%). Previous studies in humans have reported coefficients of variation from Read rebreathing tests ranging from 9 to 37% (14, 26, 27). Accordingly, we were concerned that any relatively small systematic effects of CBX on the hyperoxic CO2 ventilatory response slope might be masked by these random variations. To maximize our detection sensitivity, we used the mean of five trials to determine any given animal's hyperoxic CO2 response slope on a given day (intact or CBX) and we used 2-4 control days per animal to determine the average intact control value for each animal. Over the 2-4 control days, we found no systematic change in the group mean hyperoxic CO2 response [1.00 ± 0.12 for change in (
)I/PETCO2 on the
first control day vs. 1.03 ± 0.07 for
I/PETCO2 on the
final control day; P = 0.81]. Additionally, the
ventilatory response slopes were normally distributed within and
between animals pre-CBX.
pH Calculations
The Siggaard-Andersen nomogram was used to estimate changes in pHa during the Read rebreathing tests from the measured PETCO2 values assuming that the dogs' blood buffer slope was parallel to the normal human buffer slope and passed through the measured eupneic arterial PCO2 (PaCO2)-pH point determined for each dog on each day.The Henderson-Hasselbach equation was used to estimate changes in
cerebrospinal fluid (CSF) pH during the Read rebreathe tests assuming
no change in CSF HCO
Data Analysis
One-way ANOVA with repeated measures and Tukey post hoc tests were used to determine whether the changes in any of the measured variables after CBX were significant (P < 0.05).| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Confirmatory Tests of CBX
Ventilatory responses to intravenous bolus injections of NaCN are presented in Fig. 1. Whereas all dogs exhibited brisk, transient increases in VT after NaCN injection during control testing (mean = 155 ± 33% above eupneic VT), removal of the carotid bodies virtually eliminated this increase in all dogs days 1-4 post-CBX (12 ± 12% above eupneic VT). A partial restoration in the ventilatory response to NaCN (outside the 95% confidence interval for eupneic VT) was noted in one dog beginning day 7 (43% of intact response) and in another two dogs beginning day 14 post-CBX (30 and 41% of intact response). Sham CBX had only minor effects on the NaCN response. The increase in VT to NaCN during control and postsurgery in the sham CBX group were 174 ± 69 and 115 ± 31% above eupnea, respectively.
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The ventilatory responses to steady-state hypoxia are presented in Fig.
2. During control testing, the five dogs
hyperventilated (average PaCO2 decrease of 12 ± 5 Torr) when PaO2 was lowered to ~35 Torr. After
CBX, however, there was no significant hyperventilatory response to an
equivalent level of hypoxemia.
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The ventilatory responses of the same five dogs to steady-state hyperoxia are also presented in Fig. 2. PaO2 >500 Torr during control testing caused all five dogs to hypoventilate (average PaCO2 increase of 2 ± 1 Torr). Removal of the carotid bodies reversed the hyperoxic response in these animals so that they hyperventilated (average PaCO2 decrease of 4 ± 1 Torr) post-CBX while breathing 100% O2.
Eupnea
Blood gases.
The time course of changes in eupneic, air-breathing
PaCO2 are presented in Fig.
3. Relative to control
(PaCO2 = 40 ± 3 Torr), all dogs
hypoventilated after removal of the carotid bodies with eupneic
PaCO2 reaching a maximum of 53 ± 6 Torr three
days post-CBX. There was no significant recovery in eupneic
PaCO2 over the ensuing 18 days. Sham CBX had no effect
on eupneic, air-breathing PaCO2 (mean control = 38 and 37 Torr; mean post-sham CBX = 38 and 36 Torr).
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Ventilation and diaphragm EMG.
Measurements of eupneic ventilation and inspiratory motor output are
presented in Table 1. There were significant reductions in eupneic
I (
16 ± 16%), crural diaphragm EMG minute
activity (17 ± 5%), breathing frequency (10 ± 20%),
VT/inspiratory time (TI) (19 ± 9%),
and the rate of rise of the diaphragm EMG (13 ± 9%) when
control values were compared with the post-CBX values averaged over
days 2-21. Eupneic VT did not change significantly (7 ± 15%) after CBX. Additionally, the relationship between
eupneic diaphragm integrated EMG and VT was unaffected by
CBX. Sham CBX had no significant effects on any of the aforementioned variables.
Mean Arterial Blood Pressure. Changes in eupneic mean arterial blood pressure (MAP) are also presented in Table 1. Relative to control (MAP = 103 ± 7 mmHg), CBX elicited a significant increase in MAP on day 1 post-CBX (121 ± 8 mmHg). Resting MAP was subsequently returned to levels not different from control beginning on day 2 post-CBX (109 ± 5 mmHg). Sham CBX had no significant effects on resting MAP.
Hyperoxic CO2 Responses
Figure 4 presents the average (n = 7) beginning and end-point values of PETCO2 andI recorded
during the pre- and post-CBX hyperoxic CO2 response tests.
Whereas the starting values of I and the range of
PETCO2 covered during the CO2
response tests were similar to control, the
PETCO2 values at which the Read rebreathe tests began were ~20% greater after CBX (i.e., the response curves were shifted to the right post-CBX). Figure 4 also illustrates the
finding that the ventilatory response slopes to hyperoxic rebreathing
were reduced after removal of the carotid bodies.
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I and diaphragm EMG.
Figure 5 presents the time course of
changes in the ventilatory response to hyperoxic rebreathing after CBX.
Relative to control, the ventilatory response slopes to hyperoxic
hypercapnia (as a function of PETCO2) were
reduced 40 ± 15% (range 15 to 49%) by day 2 post-CBX with no recovery over the ensuing 19 days. When the
ventilatory response to hyperoxic hypercapnia was expressed as a
function of changes in estimated pHa or CSF pH (see Table 2), these response slopes were reduced
significantly as well after CBX (27 ± 20% vs. pHa,
and 24 ± 18% vs. CSF pH).
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I and its
components obtained during the hyperoxic CO2-rebreathe
tests. Relative to control testing, the I,
VT, and breathing frequency response slopes were reduced
34 ± 19, 39 ± 22, and 37 ± 40% respectively post-CBX. Therefore, 52% of the reduction in the ventilatory response slope to hyperoxic rebreathing was due to the reduced VT
response with the remaining 48% due to the reduced breathing frequency response. Sham CBX had no significant effects on the response slopes
for I or its components during hyperoxic rebreathing.
Table 2 also contains additional indexes of the drive to breathe during
the hyperoxic CO2 response tests before and after removal
of the carotid bodies. The response slopes of
VT/TI , rate of rise of the diaphragm EMG, and
minute diaphragm EMG activity during the Read rebreathing tests were
significantly reduced days 2-21 post-CBX by an average
of 41 ± 31, 19 ± 10, and 20 ± 9%, respectively, compared with control. Similar to eupnea, integrated diaphragm EMG vs. VT relationship during the Read
rebreathing tests were unaffected by CBX (Fig.
6).
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MAP.
Results of the MAP response during the hyperoxic CO2 tests
are contained in Table 2. In control, MAP rose an average of 0.3 mmHg
for every 1-mmHg increase in PETCO2
during the hyperoxic hypercapnic response tests. After CBX, the
slope of MAP vs. PETCO2 during the
rebreathes was significantly reduced (30 ± 7%) with respect to control.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The major findings of this study reveal that surgical removal of the carotid bodies results in marked hypoventilation and a significantly reduced ventilatory responsiveness to hyperoxic hypercapnia, indicating that peripheral chemosensitivity to CO2 is not eliminated with a hyperoxic background (PaO2 >500 Torr) as is often assumed. We also found that these changes were not time dependent, indicating a lack of aortic chemoreceptor and/or CNS compensation/adaptation for up to 3 wk after CBX.
Limitations
As shown in Fig. 2, the hyperoxic CO2 response tests post-CBX began at PETCO2 values ~10 Torr higher compared with the intact response tests. If changes in pH are the predominant mediators of changes in ventilation (10), then the fact that the pre- and post-CBX response tests started at different PETCO2 values would confound interpretation of the ventilatory response because of the log relationship of PCO2 to pH. In other words, because the post-CBX response tests started at higher PETCO2 values than the intact response tests, pH would decrease relatively less for any given increase in PETCO2 during the post-CBX response tests. Thus the magnitude of the observed decreases in the ventilatory responses to hyperoxic hypercapnia after CBX may be more artifactual than real and merely a result of our choice of stimulus (i.e.,PETCO2), which would
overestimate the actual changes in the stimulus to breathe (i.e.,
H+ concentration) during post-CBX testing. To account
for the different starting PETCO2 values
pre- and post-CBX, I was also plotted against
estimated pHa and CSF pH. Plotting I
against pHa and CSF pH separately still resulted in
ventilatory response slopes that were significantly lower after CBX,
although the reduction was approximately one-half of that seen when
ventilation was plotted against PETCO2
(Table 2).
On the other hand, plotting ventilation against either of the estimated
pH values individually seems inappropriate because acidic changes in
pHa are not the only stimulus in an intact animal (changes
in CSF pH play a role too), and plotting I against estimated changes in CSF pH alone during control testing does not
account for changes in pHa that also affect breathing.
Although the search for an appropriate independent variable with
respect to a CO2 response test in a CBX design continues,
we conclude that the carotid bodies contribute significantly to the
ventilatory response to hypercapnia, even in a hyperoxic background.
Another possible limitation of the present study is that denervation was accomplished through removal of both carotid chemo- and baroreceptors. CO2 breathing increases blood pressure, which could inhibit ventilation in the carotid body-intact (28) but not CBX animals during the hyperoxic hypercapnic challenges. This blood pressure-induced inhibition of ventilation would reduce the hyperoxic CO2 ventilatory response slope during intact, but not post-CBX, testing. This effect alone would narrow the difference between the pre- and post-CBX response slopes, causing underestimation of the carotid body contribution to the CO2 response in hyperoxia. However, MAP only changed 1-5 mmHg during the pre- or post-CBX hyperoxic CO2 response tests so that carotid sinus baroreceptors probably played a minimal role during control testing because the pressure-induced inhibition of ventilation at the carotid body is not manifested until pressures are raised >20-30 mmHg above control (16, 28). Additionally, MAP during eupneic control was different from intact only on day 1 post-CBX so that the baseline blood pressures during the pre- and post-CBX hyperoxic CO2 response tests were similar as well. This rapid recovery in the control of blood pressure after carotid baroreceptor denervation is similar to previous reports in the same species using the CBX design (22).
It is also possible that the reductions in the ventilatory response to the Read rebreathing tests after CBX were due to a smaller central CO2 stimulus during the post-CBX tests as opposed to a decrease in responsiveness of the system. More explicitly, if increases in CO2 at the carotid body cause reflex increases in sympathetic outflow that reduce brain blood flow, then CBX would eliminate this reflex sympathetic outflow, allowing for greater increases in brain blood flow during the rebreathe tests, which would blunt the rise in brain tissue PCO2 compared with the intact responses. It is unlikely, however, that this mechanism explains our findings because it has been demonstrated that CBX does not affect the cerebral blood flow response to inspired CO2 in the awake baboon (19).
Evidence for Peripheral Chemoresponsiveness
Elimination of the transient increase in ventilation after intravenous NaCN injection has been the most commonly used method of confirming peripheral chemodenervation (3, 4, 18, 24). Although CBX did indeed abolish the NaCN response in all seven of our dogs for the first 4 days post-CBX, a partial restoration in the NaCN response (outside the 95% confidence interval of control VT) was seen in one animal beginning day 7 post-CBX and another two animals beginning on day 14 post-CBX (Fig. 1). It is not clear whether this partial return in the NaCN response was originating from carotid chemosensitive tissue or was due to upregulation of aortic chemosensitivity, which has been shown to occur after CBX in the neonatal, but not adult, pig (18). Similarly, aortic chemosensitivity to hypoxia has been shown to occur in the awake cat beginning 30 days post-CBX (33). However, the fact that more than half of our denervated animals failed to show any signs of responsiveness to intravenous NaCN or to hypoxia after CBX speaks against aortic upregulation after CBX in the adult dog. Regardless of the specific mechanism of the partial return in peripheral chemosensitivity to NaCN in three of our animals, the functional impact of this partial recovery on the ventilatory control system was minimal because there were no accompanying changes in eupneic PaCO2 or the ventilatory responses to hyperoxic hypercapnia or hypoxia.Carotid Body Contribution to the Eupneic Drive to Breathe
The contribution of the carotid bodies to the eupneic drive to breathe has long been debated. Studies using acute hyperoxia to transiently silence the peripheral chemoreceptors in awake humans and dogs have found only minor reductions in ventilation (15-20%), leading to the conclusion that the carotid bodies play a minor role in the eupneic drive to breathe (9). A major assumption in these studies is that hyperoxia does indeed abolish all peripheral contribution to the eupneic drive to breathe.Conversely, findings in CBX studies reveal a more important role of the carotid bodies in the eupneic drive to breathe. Studies in the awake calf (4), pony (3), rabbit (5), rat (23), goat (24), and human (35) have found significant amounts of CO2 retention during eupnea (6-18 mmHg) after removal of the carotid bodies, which is in agreement with our findings. Marked hypoventilation after CBX indicates that removal of the carotid bodies eliminates a major contribution to the total drive to breathe because the noted decreases in ventilation post-CBX persist despite sustained acidification of the CSF (i.e., central chemoreceptors). The degree of acidification of CSF has been shown to be similar in magnitude to the acidosis measured in the plasma because pH of the two fluid compartments is regulated in a similar fashion during chronic disturbances in PCO2 (6, 29). This reduction in the drive to breathe despite a chronic CSF acidosis raises the question as to whether removal of afferent input from the carotid bodies reduces the level of responsiveness of the central chemoreceptors (see below).
Carotid Body Contribution to the Ventilatory Response to Hypercapnia
Similar to their role during eupnea, carotid body contribution to the ventilatory response to CO2 in both normoxia and hyperoxia remains a controversial topic. Results from studies in the awake (30) and anesthetized (21) cat have shown that medullary lesioning virtually abolishes the ventilatory response to normoxic hypercapnia, supporting the view that the peripheral chemoreceptors play an insignificant role in the hypercapnic ventilatory response. Interpretation of the results from these studies are confounded, however, by the fact that the exact function of the lesioned neurons remains unknown, raising the possibility that more than just chemosensitive tissues were destroyed.Conversely, studies partitioning central and peripheral chemoreception
using isolated perfusion and CBX techniques place a greater importance
on the carotid bodies with respect to CO2 responsiveness. Carotid body perfusion in the awake dog (32) has shown
that lowering PCO2 by 3-13 Torr at the
carotid body decreases I by 20-30%. Similarly,
CBX in the awake goat has shown that the carotid bodies can account for
40-50% of the whole body ventilatory responsiveness to normoxic
hypercapnia (24).
A major difference between the present study and the aforementioned is that our CO2 response tests were done in a background of hyperoxia. Hyperoxia is thought by some to virtually eliminate peripheral chemoresponsiveness and has been used simultaneously with CO2 to isolate the effects of hypercapnia on the central chemoreceptors (2, 7, 9, 20). The major assumption in these studies was that hyperoxia eliminated peripheral chemoresponsiveness. Our data do not support this interpretation, however; nor do results from carotid sinus nerve recording studies in the anesthetized cat (11, 12, 17) that showed that a high O2 background reduces, but does not eliminate, carotid chemoresponsiveness to CO2. Studies in the anesthetized cat using isolated pontomedullary perfusion (13) and carotid body denervation (1) techniques have similarly come to attribute 20-50% of the ventilatory responsiveness to hyperoxic hypercapnia to the carotid chemoreceptors.
If hyperoxia did eliminate peripheral chemoresponsiveness, one would expect to find no difference in the hyperoxic CO2 response before and after CBX because the carotid bodies would have been "chemically denervated" during the control (intact carotid body) testing. This was clearly not the case in the present study because we found a 40% reduction in the ventilatory response to hyperoxic hypercapnia after CBX. Thus we suggest that hyperoxia does not eliminate peripheral chemosensitivity; rather, we attribute ~40% of the whole body ventilatory response to CO2 in hyperoxia directly to the carotid bodies.
The reduced ventilatory responsiveness to hypercapnia after removal of the carotid bodies could result solely from the removal of the afferent carotid sinus nerve activity and/or because CBX reduces the responsiveness of central chemoreceptors to hypercapnia. The present data do not provide any insight into which of the possible mechanisms predominate in vivo, although carotid sinus nerve recording studies during progressive hypercapnia in both normoxia and hyperoxia, as mentioned earlier, have shown that a high O2 background reduces, but does not eliminate, carotid chemoresponsiveness to added CO2 (11, 12, 17). These data support the view that removal of the chemosensory afferent activity of the carotid sinus nerve accounts for most of the reduction in the hyperoxic hypercapnic ventilatory response after CBX. Data in the anesthetized pontomedullary perfused cat also support the view that central chemoresponsiveness is not affected by the status of the peripheral chemoreceptors because the ventilatory response to specific CNS hypercapnia was the same whether the peripheral chemoreceptors were being stimulated with hypoxia or suppressed with hyperoxia (34).
Applicability to Humans
As mentioned previously, the Read-type hyperoxic rebreathe test (27) was developed as a specific measure of medullary chemoresponsiveness in the awake human with the implicit assumption that hyperoxia eliminates peripheral chemoresponsiveness. Data in the thiopentone-anesthetized human support this assumption by showing that hyperoxia eliminated the rapid component of the ventilatory response to intravenously administered sodium bicarbonate to the same extent that CBX did in the anesthetized dog (36). However, results from studies in the awake human measuring the dynamic changes in ventilation to square-wave challenges of hyperoxic hypercapnia find the existence of a "fast component" in the ventilatory response, which agree with our findings and support the view that hyperoxia does not eliminate peripheral chemoresponsiveness to CO2 (8, 25). We believe that our findings in the awake dog can be applied, at least qualitatively, to the awake human.Summary
The present study showed that surgical removal of the carotid bodies results in marked hypoventilation and a significantly reduced ventilatory responsiveness to hyperoxic hypercapnia. These findings indicate that the carotid bodies are significant contributors to the eupneic drive to breathe and to the ventilatory response to CO2, even in a background of hyperoxia. The decreases in ventilatory drive and chemoresponsiveness after removal of the carotid bodies were not attenuated over time, indicating that the ventilatory control system of the adult dog is unable to compensate for the loss of carotid chemosensitive afferents.| |
ACKNOWLEDGEMENTS |
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This work was supported by National Heart, Lung, and Blood Institute Grants HL-50531 and HL-07654.
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FOOTNOTES |
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Address for reprint requests and other correspondence: J. R. Rodman, 504 N. Walnut St., Madison, WI 53705-2368 (E-mail: jrrodman{at}students.wisc.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.
Received 5 September 2000; accepted in final form 26 February 2001.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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