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Department of Physiology, University of Kentucky, Lexington, Kentucky 40536
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Xu, Fadi, and Donald T. Frazier. Involvement of the
fastigial nuclei in vagally mediated respiratory responses.
J. Appl. Physiol. 82(6):
1853-1861, 1997.
Previous studies have demonstrated that the
cerebellum, especially the fastigial nucleus (FN), is capable of
modulating respiratory responses to chemical and mechanical stimuli.
Because there is evidence to show projections from vagal afferents to
the FN, the goal of this study was to determine the role of the FN in
the respiratory reflexes elicited by activation of vagal afferents.
Experiments were performed in anesthetized (chloralose), paralyzed, and
artificially ventilated cats with an occipital exposure of the
cerebellum. Administration of capsaicin (Cap; 5-10 µg/kg) via
the right external jugular vein at the end of inspiration and
application of lung inflation (LI; 10 cmH2O) during inspiration were
carried out to stimulate nonmyelinated and myelinated vagal afferents,
respectively. The phrenic neurogram was recorded as an
index of the respiratory motor output. Control cardiorespiratory
variables [expiratory duration
(TE), arterial blood
pressure] and their immediate responses to stimuli were compared
before and after bilateral lesions of the FN. The results showed the
following. 1) Cap
injection and LI resulted in a dramatic increase in
TE (apnea).
2) FN lesions did not significantly
alter the control TE; however,
the apneic duration induced by Cap injection was prolonged.
3) Neither FN lesions nor
cerebellectomy affected the apneic duration that resulted from
application of LI. 4) Cold blockade
of the vagi (6-8°C) eliminated the respiratory responses elicited by LI but not Cap injection; vagotomy abolished the responses to both stimuli. 5) FN lesions did
not change the control ABP or its responses to either LI or Cap
injection. It is concluded that the FN is involved in vagally mediated
respiratory reflexes elicited by activation of nonmyelinated (C-fiber)
vagal afferents.
cats; respiratory control; cerebellum; lung inflation; capsaicin; apnea; differential vagal block; vagotomy
INTRODUCTION VAGAL AFFERENTS contain two type of fibers, myelinated
and nonmyelinated. Application of lung inflation (LI)
during inspiration to activate vagal myelinated fibers (2, 3, 7, 9) or delivery of capsaicin (Cap) into the pulmonary circulation via the
external jugular vein to stimulate vagal nonmyelinated C fibers (1-3, 10) leads to an inspiratory termination followed by an apnea.
Recent evidence suggests that the cerebellum, especially the fastigial
nucleus (FN) within the anterior lobe of the cerebellum, contributes to
respiratory timing regulation. It has been shown that in anesthetized
cats, depending on the stimulating frequency and site within the FN, a
brief electrical stimulation produces either an excitatory or an
inhibitory effect on respiration (17). The predominant effect is
premature termination of inspiration or expiration (19). Sustained
stimulation over several breathing cycles elicits apnea or premature
termination of either inspiration or expiration (17). Therefore, sites
within the FN are capable of mimicking the results obtained with
stimulation of vagal afferents, i.e., terminating inspiration and
inducing an expiratory apnea.
Functional linkage between vagal afferents and the cerebellum has been
provided by Hennemann and Rubia (8), who observed evoked potentials in
the cerebellar anterior lobe of the nembutalized cat when the cervical
vagus nerve was electrically stimulated. By injecting
horseradish peroxidase into various parts of the cerebellar cortex and
nuclei, Zheng et al. (25) discovered projections from the vagus nerve
to the FN in the cat.
On the basis of the above information, we hypothesized that the FN
might modulate respiratory reflexes elicited by activation of
myelinated and/or nonmyelinated vagal afferents.
Administration of Cap via the right external jugular vein and
application of LI during inspiration were carried out to stimulate
nonmyelinated and myelinated vagal afferents, respectively. The
respiratory responses were compared before and after FN lesions.
METHODS Twenty-one adult cats of either gender were anesthetized initially with
thiopental sodium (50 mg/kg ip) and maintained by chloralose (40 mg/kg
iv). To prevent brain edema during surgery, dexamethasone was injected
1 day before the experiment (4 mg) and on the day of the experiment (2 mg). 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
A tracheostomy was performed, and the trachea was connected to either a
ventilator or a lung-inflating system (detailed in LI). Tracheal pressure
(Ptr) was monitored and processed via a pressure transducer (model
PM5T, Statham). Animals were subsequently paralyzed with gallamine
triethiodide (4 mg/kg for induction followed by continuous supplement
of 4 mg · kg
1 · h1)
and artificially ventilated. A bilateral pneumothorax was performed, and the functional residual capacity of the lungs was maintained within
a normal range by adjustment of the end-expiratory pressure. In the
spontaneously breathing animals, supplemental anesthesia was
administered as needed to suppress corneal and withdrawal reflexes.
After paralysis of the animal, supplemental anesthetic was administered
when abnormal irregularities were observed in ABP, heart rate, or
respiratory rate and pattern. Tidal volume of the
ventilator was usually adjusted at 
25 ml with a frequency 
35
breaths/min to minimize inputs from afferents of the chest wall and
diaphragm. These ventilator parameters were kept constant throughout the experiment except during application of LI. End-tidal PO2 and
PCO2 were continuously monitored
(model 78356A, Hewlett-Packard) and kept at ~100 and ~30 Torr,
respectively, throughout the experiment by adjustment of the inhaled
gas mixtures. Animals were placed in a Kopf stereotaxic
apparatus, and openings were made in the occipital skull. Bleeding was
controlled by bone wax and absorbable hemostat (Surgicel and/or
Gelfoam). The dura was removed, and the underlying tissue 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 then covered with petroleum jelly to prevent drying. Raw PN signals were filtered (300-3,000 Hz) and amplified by using a Grass Instrument model P15 preamplifier before being displayed 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).
Vagal Cold Blockade
Both cervical vagus nerves were isolated for subsequent cold block or transection. To differentiate which kind of fibers are activated by Cap injection and LI, a cooling method to reversibly block vagal myelinated fibers was employed. The cooling apparatus used to block the vagi was similar to that used in our previous experiments (5). The isolated cervical vagi were placed in the groove (1.5-cm length) of a copper cooling radiator, with care being taken to minimize the tension on the nerve. During cooling, a coolant held at a constant preset bath temperature (6°C; model RM6, Brinkmann Lauda) was circulated through the copper radiator. Both nerves were simultaneously cooled to 6-8°C for ~10 min, and the vagal stimuli were repeated. After completion of the protocols, the radiators were removed and the nerves packed with cotton wads saturated with warm isotonic saline.Cap Injection
The right cervical external jugular vein was isolated, and a catheter (~1.5-mm diameter and ~40-cm length) was advanced close to the right atrium for Cap injection. The inserted depth of the catheter was determined by measuring the distance from the heart (as felt from the heartbeat) to the cannulating site before implantation. The solution of Cap (100 µg/ml) was made in a vehicle of 10% ethanol, 10% Tween 80, and 80% isotonic saline as described by Lee et al. (10).LI
The LI system consisted of a cylinder containing compressed gases (30% O2-70% N2), a flowmeter for controlling the flow speed to inflate the lungs, and a tube with an end that was opened and inserted into a water reservoir to preset the inflation pressure (positive end-expiratory pressure device). LI was carried out during inspiration by rapidly turning a three-way stopcock from the ventilator (ambient room air) to the LI system. The inflation gases from the cylinder passed through the flowmeter and subsequently to both the trachea and positive end-expiratory pressure device via a Y-type connector. Because the depth of the tube under the water and the flow speed were controlled, the lungs were constantly inflated at a given pressure by the gases from the cylinder.FN Lesions
Stereotaxic coordinates (13) were used to position a radio-frequency electrode (1-mm probe, Radionics) within the FN, and lesions were made by maintaining a tip temperature of 70°C for 2 min. The sites of lesions were histologically examined after completion of the experiment.Monitoring and Recordings
Arterial blood was sampled after general surgery and periodically measured throughout the experiment. Arterial pH was maintained within the range of 7.3-7.4. Base deficiencies were corrected by intravenous infusion of 0.5 M sodium bicarbonate as needed. ABP, PN,PN, and Ptr were monitored and recorded
throughout the experiment.
Protocol
One and one-half hours after general surgery were allowed for stabilization of the cardiorespiratory control variables. Bolus injections of Cap (5-10 µg/kg) and its vehicle were given with 30 min of recovery between each injection. The lungs were inflated during inspiration with a constant pressure of 10 cmH2O, and this inflation was sustained until the onset of the next PN burst (inspiration). LI was repeated 3 times with an interval of at least 10 normal breaths. The two types of stimuli were delivered randomly in four groups of animals. Group I. The protocols were conducted before and after bilateral thermal lesion of the FN to investigate the role of the FN in vagally mediated respiratory responses (n = 8). To determine whether the respiratory responses produced by LI and Cap injection were dependent on vagal afferents, the same protocols were repeated in five of these eight cats after bilateral vagotomy. The Cap injection was carried out 1 h after FN lesions and bilateral vagotomy. Group II. Because FN lesions failed to affect the LI-induced response, subsequent cerebellectomies were performed in five cats to test whether other areas of the cerebellum may be involved. Cerebellectomy was accomplished by using a blunt spatula to transect the cerebellar peduncles followed by aspiration of the cerebellar tissue (method detailed in Ref. 23). The exposed cut surface was gently packed with absorbable hemostat (Surgicel and/or Gelfoam) and covered with mineral oil. One hour after cerebellectomy, the LI protocol was repeated. Group III. To distinguish which type of vagal fibers (myelinated or unmyelinated) was activated by Cap injection and LI, respectively, reversible cold block of the cervical vagi was employed (n = 5). The previous protocols were repeated after the cervical vagi were cooled to 6-8°C and rewarmed to 37°C. In three of these animals, the cooling protocol was repeated and respiratory responses to Cap injection and LI tested again. Group IV. A sham-operated time control was conducted in five cats (2 of these cats were subsequently utilized for group III studies) to clarify whether the time course of Cap administration would affect the apneic duration. Respiratory control values and the responses to Cap injection were measured every 1.5 h for 4.5 h (3 tests) after the completion of the general surgery. The interval between the Cap injections in the three tests was similar to the interval applied in the intact, FN-lesioned, and vagotomized preparations.Histological Examination
The animals were euthanized by administration of additional anesthetic, and the brain stem and the cerebellum were removed and placed in 10% Formalin. After at least 3 days of immersion fixation, the brain stem and the cerebellum were frozen, and 50-µm sections were cut and mounted. The placement of the lesions was drawn with camera lucida.Data Analysis
Control TE and ABP in the different preparations were expressed as absolute values. Responses to stimulation were presented as percent change from control. Latency and respiratory recovery time (absolute values) were determined from the interval between the onset of Cap delivery and the initiation of apnea and between the beginning of the apnea and the point at which PN returns to control level, respectively. For Cap injection, these variables (control and response) were compared before and after FN lesions and vagotomy, with and without vagal cold blockade, and among the first, second, and third sham-operated time controls. These variables were also compared before and after FN lesions/vagotomy and cerebellectomy for LI. Control respiratory values were measured and averaged from the five breaths before the application of the stimuli, whereas only the responses of the expiratory phase of the first breath immediately after Cap injection or during LI application were analyzed. ABP was measured 30 s before and immediately after stimulation. All data are presented as means ± SE. A one-way analysis of variance with repeated measurement and the Student-Newman-Keuls post hoc test were used to identify significance of the differences among 1) the control values (intact vs. FN lesioned vs. vagotomized or cerebellectomized), 2) the responses obtained from different preparations (with and without vagal cold blockade), and 3) the responses derived from the sham-operated time controls. P values <0.05 were considered significant.RESULTS
The typical cardiorespiratory responses to Cap injection and LI are
depicted Fig. 1,
A and
B, respectively. Cap injected at the
end of inspiration produced three cardiorespiratory responses: 1) an immediate premature
termination of inspiration followed by an apnea (~5 s) with a latency
of ~1.8 s, 2) an attenuation of
the peak values of PN for ~30 s after restoration of the respiratory rhythm, and
3) biphasic responses of ABP (an
initial increase followed by a decrease). When the lungs were inflated
during inspiration (Fig. 1B), an
apnea appeared immediately, in contrast to the control
response. This apnea was associated with a brief period
of hypotension.
PN, respectively), and tracheal pressure (Ptr).
, Onset of stimuli. Dashed line, expiratory duration (apnea);
solid line, recovery time from capsaicin injection. Cap injection,
capsaicin injection (5 µg/kg).
Figure 2 illustrates group data of the
apneic duration elicited by Cap injection
(A) and LI
(B) before and after FN lesions (also see Table 1). As shown
in Fig. 2A, vehicle injection did not
affect the TE before and after
FN lesions. In the intact cat, Cap injection resulted in an apneic
duration 193% longer than control (3.25 ± 0.33 vs. 1.16 ± 0.15 s). Subsequent FN lesions produced apneic durations significantly
longer (4.50 ± 0.39 s) than those observed in the intact
preparation, i.e., 341% increase from control. As listed in Table 1,
the values of latency and recovery time in the intact cat were not
significantly different from the data obtained after FN
lesions. The recovery time showed considerable individual
variation, ranging from 20 to 120 s. With respect to LI (Fig.
2B),
TE was markedly increased by
245.0 ± 41.7% compared with control (3.9 ± 0.36 vs. 1.22 ± 0.10 s) when 10 mmH2O pressure
were utilized to inflate the lungs. This apneic duration was not
significantly altered by FN lesions.
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Cap injection induced an initial increase (phase I) and secondary decrease (phase II) in ABP (see Table 1). Both phase I and II responses were significantly different from their control. In contrast, application of LI resulted in a hypotension. FN lesions did not significantly alter ABP responses to Cap injection or LI.
Figure 3 presents a cross section of the
brain stem and the cerebellum to show regions where lesions were made.
For the data reported, all lesioned regions denoted by stippled areas
were histologically confirmed to include the medial portion of the FN
and its adjacent areas; i.e., the ventral portion was partially ablated, and, in three cats, the margin of the lesions extended slightly beyond the dorsal border of the FN. Most
lesioned areas were spherical with a diameter of 1.8-2.4 mm. In
previous studies, the region of the FN, particularly its medial and
ventral portions, has been demonstrated to be involved into respiratory
regulation (17, 19, 22).
To test whether other areas of the cerebellum may be involved in the respiratory responses to LI, cerebellectomy after FN lesions was carried out in five cats. The TE response to LI obtained in the intact, FN-lesioned, and cerebellectomized preparations are compared in Table 1. Although cerebellectomy tended to prolong the apneic duration elicited by LI, this prolongation was not significantly different from that observed in the intact preparation.
The questions as to whether the respiratory responses observed were
mediated by vagal afferents and, if so, which types of fibers
(nonmyelinated and/or myelinated) were addressed in the present
studies. To answer the first question, the respiratory responses to
these stimuli were recorded in bilaterally vagotomized cats. As
displayed in Fig. 4, the prolongation of
TE (apneic response) produced by
Cap injection and LI (see Fig. 1) was eliminated after bilateral
vagotomy. This effect of vagotomy was confirmed by the group data
(Table 1).
PN, and Ptr.
Top: capsaicin injection-induced
responses. Bottom: lung
inflation-elicited responses.
To answer the second question, we employed reversible differential
cooling of the cervical vagi to 6-8°C because it is well documented that myelinated vagal fibers are inactivated at this temperature with no significant effect on the conduction of
nonmyelinated (C) fibers (3). Figure 5
shows an example of the effect of vagal differential cold blockade on
the respiratory responses to Cap injection and LI. Before cooling (Fig.
5A), Cap injection and LI resulted
in an apnea. When vagi were cooled to 6°C (as presented in Fig.
5B), the control values of peak
PN were increased and respiratory frequency
decreased. Whereas vagal cold blockade had no qualitative effect on the
responses to Cap injection, it did eliminate the responses normally
evoked by LI. After rewarming of vagi (Fig.
5C), the prolongation of control TE disappeared and the apneic
responses to LI reappeared. The group data showed that the Cap-induced
apnea and ABP responses were not significantly affected by selective
blockade of vagal myelinated afferents (Fig.
6A). In
contrast, the apneic response to LI disappeared when the vagi were
cooled to 6-8°C, whereas the ABP response (hypotension) was
not affected (Fig. 6A).
The effects of surgical treatments on control values of TE and ABP are also listed in Table 1. Compared with the data obtained in the intact preparation, FN lesions and/or cerebellectomy did not significantly alter TE or ABP; however, bilateral vagotomy markedly prolonged TE and increased ABP.
A sham-operated time control was performed to clarify whether the time course of the injection of Cap would affect the apneic duration. Control TE and ABP and their responses to Cap injections were measured three times within a 4.5-h period after the completion of the general surgery. The cardiorespiratory responses (TE, latency, recovery time, and ABP) to the first, second, and third Cap injections are compared in Table 2. No significant differences were found among the data obtained over the time course of the experiments.
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DISCUSSION
In the present experiments, the paralyzed preparation was utilized instead of spontaneously breathing cats for two reasons. First, it was employed to reduce confounding inputs from respiratory muscles. The paralyzed preparation with a bilateral pneumothorax and lower pump volumes significantly reduces inputs from respiratory muscles normally activated in spontaneous breathing cats. Inputs emanating from diaphragm and intercostal muscles, for example, have been demonstrated to interact with the cerebellum to modulate respiratory responses (5, 23). Second, use of the ventilator also minimizes variation of tidal volume and thereby maintains inputs from pulmonary mechanoreceptors and, to some extent, chemoreceptors, relatively constant.
The major findings in these experiments were that FN lesions did not significantly change the eupneic (control) expiratory duration or the respiratory response to LI but did prolong the apneic duration induced by Cap injection into the pulmonary circulation. These results suggest that the FN has an inhibitory effect on the respiratory response to Cap injection. The fact that the FN and cerebellum contributed little to the LI-induced apnea was surprising because respiratory-related neurons within the FN were found to respond to activation of vagal mechanoreceptors (19). A feasible interpretation for this contradictory finding is that the population of FN respiratory neurons responsive to vagal stimulation is so small that their contribution to modulation of the apnea induced by LI is limited.
An interesting result in the present study was the differential effect the FN exerted on respiratory responses evoked by vagal C fibers (unmyelinated) compared with myelinated. First, we confirmed that bilateral vagotomy abolished the apneic responses to Cap injection and LI, indicating that these responses are dependent on intact vagal afferents. Second, by using cold blockade (6-8°C) to differentiate vagal myelinated fibers from C fibers (Fig. 5), we found that cooling did not eliminate the apneic response to Cap injection but did abolish the apneic response to LI. As reviewed by Coleridge and Coleridge (2), the average cold blockade of impulse conduction in myelinated fibers was achieved at a temperature between 6 and 8°C, whereas conduction in nonmyelinated fibers (C fibers) continues at temperatures several degrees lower. Our data are in agreement with a number of previous studies in dogs, cats, and rats in which the effects of Cap injection depended on the activation of pulmonary C fibers (2, 10, 16) and LI-induced apnea was related to vagal myelinated fibers (3, 23).
There is evidence to support a cerebellar role in vagally mediated respiratory reflexes. Direct anatomic projections from vagal axons to the FN have been demonstrated by utilizing injections of horseradish peroxidase into the FN and tracing the projections to the vagal nucleus in the cat (25). Functionally, electrophysiological studies have shown that, in the cat, evoked potentials were recordable in the cerebellar anterior lobe to cervical vagus nerve stimulation (8). Moreover, FN lesions or cerebellectomy significantly altered the stimulus parameters necessary to produce a vagally mediated premature inspiratory termination. Interestingly, this modulation was not observed on the inspiratory termination elicited by superior laryngeal and intercostal nerve stimulation (24). Cerebellar-vagal interactions in the regulation of respiration have also been demonstrated in other studies. For example, Williams et al. (18) found that removal of the cerebellum decreased inspiratory and expiratory duration, but these changes were no longer obtained if cerebellectomy was subsequently followed by bilateral vagotomy. Similarly, cerebellectomy-induced reduction of respiratory frequency in response to progressive hypercapnia was absent after bilateral vagotomy before cerebellectomy (21), implying that the facilitatory effect of the cerebellum on respiratory timing is dependent on the intact vagi. The dependency of the cerebellar effect on respiratory frequency response to hypercapnia may be linked to cerebellar modulation of pulmonary C fibers inputs because investigators have indicated that pulmonary C-fiber endings are able to act as CO2 chemoreceptors (12, 15).
In the present study, we did not attempt to identify whether cell bodies or fibers of passage within the FN were involved in the respiratory responses to activation of pulmonary C fibers. The assumption that cerebellar neurons are responsible for this modulation is supported by some previous studies. Electrical stimulation of the FN has been reported to alter respiration, and this modulation disappeared after microinjection of kainic acid into the FN. This finding suggests the involvement of cell bodies in the induced respiratory responses because fibers of passage are spared by kainic acid (19). Moreover, there are respiratory-modulated neurons within the FN, the firing behavior of which can be altered by manipulation of vagal afferent inputs (11, 20).
The lack of effect of FN lesions and cerebellectomy on eupneic breathing is in concordance with other investigators' observations. During eupneic breathing, it has been reported that cerebellectomy has little effect on minute ventilation, diaphragm electromyographic activity, and inspiratory activity of phrenic efferents in decerebrate and anesthetized cats (14, 22, 23). Similarly, ablation of the FN failed to significantly alter respiration in the cat (20, 21). These results suggest that the cerebellum is not critical in the control of eupneic breathing. However, it is fair to point out that some previous studies reported that in unanesthetized (decerebrated) cats, ablation of the cerebellum increased respiratory frequency (4) or tidal volume (6), whereas, in anesthetized cats, removal of the cerebellum or the FN reduced the respiratory frequency (18).
The latency of Cap effect observed in our experiments (~1.8 s) is very close to previous studies carried out in cats. By recording the vagal C-fiber activity, Armstrong and Luck (1) found that Cap (10 µg/kg) injected into the right jugular vein produced a burst of impulses with a latency of 2.1 s. Toh et al. (16) indicated that Cap injection resulted in an apnea (arrested breathing in expiration) with a latency of ~1.5 s. With regard to the apneic duration, it has been reported that Cap injection (20-25 µg/kg) led to an apneic duration that persisted ~30 s in dogs (2) and ~20 s in cats (16), whereas a lower dose of Cap (0.5-1 µg/kg) produced apneic duration for ~3 s in rats (10). Our experiments, which utilized a modest concentration of Cap (5-10 µg/kg), resulted in an apneic duration of ~3.3 s. The variations in apneic duration reported are explicable on the basis of the differences of Cap dose administered, mode of injection (via jugular vein into pulmonary circulation or via femoral vein into systemic circulation), and animal species. LI applied in our experiments led to an apnea (for ~4 s) associated with hypotension. Similarly, Grinten et al. (7) showed that in anesthetized cats addition of 1 kPa pressure to Ptr (ambient pressure) led to an apnea noted on the PN for ~4 s, which was associated with an evident decrease in ABP. Lee and colleagues (9) reported that in conscious dogs LI with Ptr of 10 cmH2O at the onset of inspiration induced an 3- to 5-s apnea and hypotension.
A biphasic ABP response to Cap injection was found in our experiment, which was characterized by an initial transient increase followed by a decrease. The same biphasic responses of ABP to Cap injection were also observed in rats when Cap (0.5 µg/kg) was delivered into the right jugular vein (10). The mechanisms involved in the initial increase of ABP (phase I) remain unclear, but the secondary decline of ABP (phase II) has been postulated to be due to pulmonary C-fiber inhibitory effect on the cardiovascular system. It is reasonable to presume that Cap- or LI-induced ABP responses may reflexly affect respiration via arterial baroreceptor reflexes. For instance, Cap injection-induced hypertension may activate arterial baroreceptors, which, in turn, inhibit inspiration. However, our finding that FN lesions did not significantly affect the ABP response to Cap injection and LI, but did alter the Cap-induced apneic duration, suggests that the FN modulation of the apnea is not secondary to activation of arterial baroreceptor reflexes.
In summary, we observed that FN lesions did not significantly change LI-induced apneic duration but prolonged Cap-induced apnea. Vagotomy abolished the responses to both stimuli; however, cold block of the vagi (6-8°C) eliminated the responses to LI without effect on the Cap induced-responses. FN lesions failed to affect the control respiration and ABP responses to either LI or Cap injection. We conclude that the FN is not involved in the LI-induced apnea that primarily results from activation of myelinated vagal fibers. However, the FN does attenuate the respiratory reflexes mediated by Cap-activated vagal C fibers.
ACKNOWLEDGEMENTS
The authors express their appreciation to members of the University of Kentucky respiratory group for helpful critiques and to Dr. Lu-Yuan Lee for advise in designing the protocol of Cap injection.
FOOTNOTES
Address for reprint requests: D. T. Frazier, Dept. of Physiology, Univ. of Kentucky, Lexington, KY 40536.
Received 11 October 1996; accepted in final form 3 February 1997.
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