Hypoglossal Activity Research Articles

Endogenous calcium buffering in motoneurones of the nucleus hypoglossus from mouse.

1. Simultaneous patch clamp and rapid microfluorometric calcium measurements were performed on sixty-five motoneurones in slices of the nucleus hypoglossus in the brainstem of 2- to 6-day-old mice. 2. Hypoglossal motoneurones were particularly vulnerable to mechanical or metabolic stress during isolation of in vitro slice preparations. Therefore, experimental conditions were optimized for functional integrity, as judged by spontaneous rhythmic activity of hypoglossal nerves (XII). 3. Calcium concentrations in the cell soma were monitored with a temporal resolution in the millisecond time domain during depolarizing voltage steps. Ratiometric fluorescence measurements were made using a rapid monochromator (switching tau < 10 ms), a photomultiplier tube and the calcium sensitive dyes fura-2 and mag-fura-5. 4. Dynamics of somatic calcium transients were investigated as a function of the concentration of calcium indicator dye in the cell. Decays of calcium transients were approximated to a single exponential component and decay time constants showed a linear dependence on dye concentration. The extrapolated decay time in the absence of indicator dye was 0.7 +/- 0.2 s, suggesting rapid somatic calcium dynamics under physiological conditions. 5. By a process of back-extrapolation, the 'added buffer' method, a calcium binding ratio of 41 +/- 12 (9 cells) was obtained indicating that 98% of the calcium ions entering a hypoglossal motoneurone were bound by endogenous buffers. 6. Endogenous calcium binding ratios in hypoglossal motoneurones were small compared with those of other neurones with comparable size or geometry. Accordingly, our measurements suggest that the selective vulnerability of hypoglossal motoneurones to calcium-related excitotoxicity might partially result from low concentrations of calcium buffers in these cells.

Role of the medullary raphe nuclei in the respiratory response to CO 2

We characterized the role of neurons within the midline of the medulla oblongata on phrenic and hypoglossal nerve responses to hypercapnia during early development. Studies were performed on decorticate or anesthetized, vagotomized and mechanically ventilated 14–20 day old piglets. Reversible withdrawal of midline neuronal activity was induced by microinjections of lidocaine (2%, 300 nl; n=10) and lesioning was caused by microinjections of the neurotoxic agent, ibotenic acid ( n=12), at the same sites. At any given end-tidal CO 2, peak phrenic and hypoglossal activities after lidocaine were significantly lower than in the control period ( P<0.01). Similarly, 1–2 h after injections of ibotenic acid, both phrenic and hypoglossal nerve responses to CO 2 were significantly lower than in the control period ( P<0.01). The results indicate for the first time that the medullary midline neurons are required for full expression of ventilatory responses to hypercapnia and raise the possibility that dysfunction of these nuclei may contribute to respiratory instability during early postnatal life.

P2 Receptor Excitation of Rodent Hypoglossal Motoneuron ActivityIn VitroandIn Vivo: A Molecular Physiological Analysis

The role of P2 receptors in controlling hypoglossal motoneuron (XII MN) output was examined (1) electrophysiologically, via application of ATP to the hypoglossal nucleus of rhythmically active mouse medullary slices and anesthetized adult rats; (2) immunohistochemically, using an antiserum against the P2X2 receptor subunit; and (3) using PCR to identify expression of P2X2 receptor subunits in micropunches of tissue taken from the XII motor nucleus. Application of ATP to the hypoglossal nucleus of mouse medullary slices and anesthetized rats produced a suramin-sensitive excitation of hypoglossal nerve activity. Additional in vitro effects included potentiation of inspiratory hypoglossal nerve output via a suramin- and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS)-sensitive mechanism, XII MN depolarization via activation of a suramin-sensitive inward current, decreased neuronal input resistance, and a slow-onset theophylline-sensitive reduction of inspiratory output likely resulting from hydrolysis of extracellular ATP to adenosine and activation of P1 receptors. Immunohistochemically, P2X2 receptors were detected in inspiratory XII MNs that were labeled with Lucifer yellow. These data, combined with identification of mRNA for three P2X2 receptor subunit isoforms within the hypoglossal nucleus (two of which have not been localized previously in brain) and the previous demonstration that P2X receptors are ubiquitously expressed in cranial and spinal motoneuron pools, support not only a role of P2 receptors in modulating inspiratory hypoglossal activity but a general role of P2 receptors in modulating motor outflow from the CNS.

Sites Other Than Ventrolateral Medullary Chemoreceptive Regions Contribute to Hypercapnic Responses During Development. † 1492

During postnatal maturation, development of respiratory activity and hypercapnic responses is controlled by a network of chemosensory cells that senses changes in CO2 and H+ ion concentration. The ventrolateral medulla is considered the primary site for central chemosensitivity, however, brain stem midline neurons have also been shown to contribute to ventilatory control of upper airway and chest wall muscle activities. In this study we sought to characterize the role of specific neurons within the midline brainstem at the so-called raphe obscurus on phrenic and hypoglossal nerve responses to hypercapnia during development. Studies were performed in ten decorticate, vagotomized, paralyzed and mechanically ventilated 14 to 20 day old piglets. Blockade of raphe obscurus neuronal activity induced by microinjections of lidocaine was associated with a significant reduction of phrenic and hypoglossal nerve responses to progressive hypercapnia. At any given end-tidal CO2, peak phrenic and hypoglossal nerve activities were significantly lower following blockade than in the control period. For example, at 7.5% CO2 phrenic activity (in arbitrary units) was 33.9±1.9 vs 18.3±4.1 (p<0.005, mean ± SEM) prior to vs following lidocaine blockade respectively. Corresponding hypoglossal activity was preferentially reduced to a greater degree than phrenic activity. for example, at 7.5% CO2 hypoglossal activity was 20.8±3.6 vs 5.6±2.1 (p<0.005) prior to vs following lidocaine blockade respectively. Injection of saline (control) solution at the same site had no effect. We conclude that impaired function of raphe obscurus midline neurons reduces respiratory responses to central chemosensory stimulation. We speculate that specific neuronal sites within the midline region of the brainstem are required for full expression of ventilatory responses to hypercapnia, and raise the possibility that alteration in their function may contribute to respiratory instability during early postnatal life.

Influence of lung volume on respiratory responses to spontaneous bladder contractions

Spontaneous bladder contractions (SBCs) in decerebrate, vagotomized, paralyzed, ventilated cats have been shown to decrease phrenic and hypoglossal inspiratory nerve activities, as well as the activities of other respiratory motor nerves. To determine whether vagal afferents from the lung influence the respiratory inhibition associated with SBCs, we recorded phrenic and hypoglossal nerve activities in decerebrate, paralyzed, vagally intact cats. The animals were ventilated by a servo-respirator, which inflated the lungs in accordance with integrated phrenic nerve activity. Maintained increases in end-expiratory lung volume were produced by the application of 2–10 cm H 2O positive end-expiratory pressure (PEEP). SBCs were accompanied by decreases in both phrenic and hypoglossal peak integrated nerve activities, as well as by marked decreases in respiratory frequency. The reduction of respiratory frequency was greater with higher levels of PEEP, a few animals becoming apneic during SBCs. After bilateral vagotomy, SBCs continued to decrease phrenic and hypoglossal peak integrated nerve activities as previously reported, but the reduction of respiratory frequency was much less striking than when the vagi were intact. These results indicate that activity of vagal afferents from the lung augments the respiratory influence of SBCs. Furthermore, SBCs in vagally intact animals can induce periodic breathing.

Roles of the pontine pneumotaxic and micturition centers in respiratory inhibition during bladder contractions

In decerebrate or anesthetized cats with moderately distended urinary bladders, spontaneous bladder contractions (SBCs) have been shown to decrease phrenic and hypoglossal nerve activities. To determine the involvement of both the pontine micturition center (PMC) and the pneumotaxic center in the respiratory response to SBCs, we recorded phrenic and hypoglossal nerve activities in decerebrate, paralyzed, vagotomized, artificially ventilated cats. Electrical stimulation of the PMC in cats with subthreshold bladder volumes below the threshold for SBCs elicited both increases in intravesical pressure (IVP) and attenuation of respiratory motor nerve activities. Respiration was not altered after PMC lesions, which abolished SBCs, contractions in response to PMC stimulation, and respiratory inhibition due to passive bladder distension. Electrical stimulation of the pneumotaxic center altered respiratory motor nerve activities and increased IVP in cats with subthreshold bladder volumes. Pneumotaxic center lesions caused apneusis, but did not abolish the SBCs, which continued to attenuate the apneustic respiratory motor nerve activity. These results indicate that the PMC is an important component of the reflex pathway from urinary bladder distension to respiratory inhibition, whereas the pneumotaxic center does not appear to be an essential part of this pathway.

Hypoxia-induced long-term facilitation of respiratory activity is serotonin dependent

Repeated isocapnic hypoxia evokes long-term facilitation (LTF) of phrenic nerve activity in rats. We wished to determine: (1) whether hypoxia-induced LTF is serotonin dependent; and (2) whether hypoxia-induced LTF is a property of upper airway motoneurons. Phrenic and hypoglossal nerve activities were recorded in urethane anesthetized, vagotomized, paralyzed and artificially ventilated rats ( n = 7). Rats were exposed to three, 5-min hypoxic episodes ( Fi o 2 = 0.10) separated by 5 min of hyperoxia ( Fi o 2 = 0.50). One hour after the final hypoxic episode, integrated phrenic and hypoglossal amplitudes and burst frequency were increased above control values (63 ± 17%, 78 ± 26% and 9.6 ± 2.1 bursts/min, respectively; p < 0.05). In rats pretreated with methysergide ( n = 7; 4 mg/kg), no changes in phrenic or hypoglossal activity from pre-stimulus control values were observed at any time post-stimulation. The results indicate that hypoxia-induced LTF requires 5-HT receptors and is characteristic of both hypoglossal and phrenic motor output.

Serotonergic effects on hypoglossal neural activity and reflex responses

We determined the effects of serotonin (5HT; 6 concentrations ranging from 0.005 to 500 μM) pressure microinjection into the hypoglossal (XII) motor nucleus (100–500 nl; pH = 7.2–7.4) on XII whole nerve activity and reflex response to upper airway negative pressure in 15 decerebrated, vagotomized, paralyzed and artificially ventilated cats. Increasing 5HT concentration resulted in a concentration dependent increase in ipsilateral tonic XII activity, with no change in phasic XII activity. Threshold concentrations ranged from 0.005 to 0.5 μM, with the maximal response reached at 5 μM. Increasing 5HT concentration also increased the duration of the XII response. This ranged from 50 s with 0.5 μM, to over 10 min with 500 μM 5HT. However, 5HT did not significantly change the XII whole nerve reflex response to upper airway negative pressure (−20 cm H 2O) at any 5HT concentration ( n = 5). All 5HT effects were reversed by microinjection of 1.0 mM methysergide. We conclude that XII responses to 5HT are elicited at low concentrations of 5HT, which have a relatively short duration of effect, but that 5HT at the XII motor nucleus has no effect on the XII reflex response to upper airway negative pressure.

Serotonergic effects on hypoglossal neural activity and reflex responses

We determined the effects of serotonin (5HT; 6 concentrations ranging from 0.005 to 500 μM) pressure microinjection into the hypoglossal (XII) motor nucleus (100–500 nl; pH = 7.2–7.4) on XII whole nerve activity and reflex response to upper airway negative pressure in 15 decerebrated, vagotomized, paralyzed and artificially ventilated cats. Increasing 5HT concentration resulted in a concentration dependent increase in ipsilateral tonic XII activity, with no change in phasic XII activity. Threshold concentrations ranged from 0.005 to 0.5 μM, with the maximal response reached at 5 μM. Increasing 5HT concentration also increased the duration of the XII response. This ranged from 50 s with 0.5 μM, to over 10 min with 500 μM 5HT. However, 5HT did not significantly change the XII whole nerve reflex response to upper airway negative pressure (−20 cm H 2 O) at any 5HT concentration ( n = 5 ). All 5HT effects were reversed by microinjection of 1.0 mM methysergide. We conclude that XII responses to 5HT are elicited at low concentrations of 5HT, which have a relatively short duration of effect, but that 5HT at the XII motor nucleus has no effect on the XII reflex response to upper airway negative pressure.

Changes in eye blink responses following hypoglossal-facial anastomosis in the cat: evidence of adult mammal motoneuron unadaptability to new motor tasks.

Hypoglossal-facial anastomosis is used in humans to restore the activity of the mimic musculature following irrecoverable facial nerve lesions. As eyelid movement kinetics is very well known, we have used this experimental model in cats to follow the evolution of blink responses and the adaptability of hypoglossal motor pools to new motor tasks. Although the electromyographic activity of the orbicularis oculi muscle in response to corneal air puffs, flashes of light or electrical stimulation of the supraorbital nerve was not recovered in the seven months following this crossed anastomosis, reflex blinks were got back by the increased activity of the retractor bulbi and extraocular recti muscles. The lid of the anastomosed side oscillated in perfect synchronization with tongue movements during licking, while it was severely affected in its motor function during optokinetic stimulation because of the spontaneous appearance of tongue-related hypoglossal activity. Present results suggest that adult mammal motoneurons are unable to readapt their motor programs to the kinetic needs of new motor targets and that most of the functional recovery observed in the cat was achieved by the compensatory hyperactivity of motor systems not directly affected by the surgery.

Optical imaging of respiratory burst activity in newborn rat medullary block preparations

We report on the optical imaging of excitation propagation induced by electrical stimulation of the nucleus tractus solitarius (NTS) area and subsequent inspiratory burst activity in the ventrolateral medulla (VLM) of a medullary block preparation. A medullary block preparation with a thickness of 1.0–1.4 mm was made from brainstems isolated from 0- to 4-day-old rats and stained with a fluorescent voltage-sensitive dye, RH795. Neuronal responses in the VLM evoked by electrical stimulation were recorded as a fluorescence change using an optical recording apparatus with a 128 × 128 photodiode array and a maximum time resolution of 0.6 ms. Motoneuronal activity was simultaneously recorded at the contralateral hypoglossal nerve roots. Neuronal excitation evoked by stimulation of the NTS area propagated to the VLM through the intermediate reticular zone (IRt). In contrast, caudal VLM stimulation induced excitation which propagated to the rostral VLM without any detectable excitation propagation in the IRt toward the NTS area from the VLM. NTS stimulation also induced an inspiratory burst activity in the hypoglossal nerve root activity with a 150–200 ms delay. Fluorescence changes corresponding to the inspiratory burst activity were observed in the VLM which coincided with the area in which the localization of many respiratory neurons had been demonstrated in previous studies using whole-brainstem preparations. The present results show the feasibility of using optical recordings for the analysis of respiratory neuron activity as well as for analysis of the transmission pathway of afferent and/or efferent information in the medulla.

Vestibular influences on hypoglossal nerve activity in the cat

The purpose of the present study was to determine if selective activation of vestibular receptors during movement produces changes in hypoglossal nerve activity. Responses were recorded from the hypoglossal nerves during trapezoidal and sinusoidal head rotations in cats with extensive denervations to eliminate non-labyrinthine inputs that could be produced by the movements. Large (50°) nose-up trapezoidal tilts produced an increased in nerve discharge; ear-down tilt was also effective in one-fourth of the animals. The responses to nose-up tilt were abolished following intracranial transections of the VIIIth cranial nerves. Smaller (20°) sinusoidal head rotations in the roll, pitche and yaw planes were ineffective in producing responses. These data suggest that vestibular inputs elicited by nose-up pitch contribute to tongue protrusion and participate in maintaining airway patency by preventing the tongue from falling to the back of the mouth.

Optical imaging of respiratory burst activity in newborn rat medullary block preparations

We report on the optical imaging of excitation propagation induced by electrical stimulation of the nucleus tractus solitarius (NTS) area and subsequent inspiratory burst activity in the ventrolateral medulla (VLM) of a medullary block preparation. A medullary block preparation with a thickness of 1.0–1.4 mm was made from brainstems isolated from 0- to 4-day-old rats and stained with a fluorescent voltage-sensitive dye, RH795. Neuronal responses in the VLM evoked by electrical stimulation were recorded as a fluorescence change using an optical recording apparatus with a 128 × 128 photodiode array and a maximum time resolution of 0.6 ms. Motoneuronal activity was simultaneously recorded at the contralateral hypoglossal nerve roots. Neuronal excitation evoked by stimulation of the NTS area propagated to the VLM through the intermediate reticular zone (IRt). In contrast, caudal VLM stimulation induced excitation which propagated to the rostral VLM without any detectable excitation propagation in the IRt toward the NTS area from the VLM. NTS stimulation also induced an inspiratory burst activity in the hypoglossal nerve root activity with a 150–200 ms delay. Fluorescence changes corresponding to the inspiratory burst activity were observed in the VLM which coincided with the area in which the localization of many respiratory neurons had been demonstrated in previous studies using whole-brainstem preparations. The present results show the feasibility of using optical recordings for the analysis of respiratory neuron activity as well as for analysis of the transmission pathway of afferent and/or efferent information in the medulla.

Effects of ethanol on respiratory activity in the neonatal rat brainstem-spinal cord preparation

Ethanol (1–12 mM) added to the superfusion medium of the isolated brainstem-spinal cords of newborn rats did not affect phrenic activity but significantly reduced hypoglossal activity by 54%, 67% and 55% at 3, 6 and 12 mM, respectively. Although the reasons for the suppression of hypoglossal activity remain unknown, this preparation may be a useful model for determining why cranial motoneurons are more vulnerable than phrenic motoneurons to various agents and, more generally, how ethanol impairs neural function.

Rhythm generation in the segmented hindbrain of chick embryos.

1. The embryonic hindbrain of chick is segmented until stage 24, when it starts to generate rhythmic activities in cranial nerves. In order to recognize a possible influence of segmentation on the organization of neuronal systems generating motor rhythms, the activity of trigeminal, facial, glossopharyngeal, vagal and hypoglossal nerves was studied during embryonic stages 24-36, by simultaneous recording of different cranial nerves in an isolated, superfused chick hindbrain preparation. 2. Highly correlated recurrent episodes of cyclical burst discharges occurred in all nerves studied (correlation coefficients, 0.8 +/- 0.1) throughout stages 24-36. 3. Such coactivation is unlikely to be due to monosynaptic connections between widely divergent premotor neurons and motoneurons, or between motoneurons themselves, because no short-term correlation was apparent in the millisecond range between activities of different motor nerves. 4. Complete transverse or midsagittal sectioning of the hindbrain disrupted coactivation of nerves located at distinct rostrocaudal levels or occupying an ipsi- or contralateral position, respectively, while sparing the ability of individual nerves to generate rhythmic activity. Each hindbrain segment thus contains bilaterally the motor nuclei together with their own rhythm generator. Coactivation of motor patterns appears to result from intersegmental and cross-median connections between these rhythm generators. 5. The results are in keeping with the hypothesis of a segmental organization of the primordial hindbrain rhythm generator and give further support to the early determination of both the anatomical and the functional fate of neurons in this region of the vertebrate central nervous system.

Effect of I1-imidazoline receptor activation on responses of hypoglossal and phrenic nerve to chemical stimulation.

Sedation elicited by some centrally acting antihypertensive agents may interfere with respiratory control, and by selectively inhibiting upper airway dilating muscle activity it may facilitate obstructive sleep apnea. Autoradiographic studies with [125I]p-iodoclonidine in the presence of 10 microM epinephrine to block alpha 2-adrenergic sites or 100 nM moxonidine to mask I1-imidazoline sites show that both I1- as well as alpha 2-sites are localized in putative chemosensory areas of the rostral ventrolateral medulla in the cat. We sought to determine the effect of activating I1 and alpha 2-receptors on central chemosensitivity by using moxonidine as a selective I1 agonist, clonidine as a mixed I1/alpha 2 agonist, SK&F-86466 as a specific alpha 2-antagonist, and efaroxan as a mixed I1/alpha 2 antagonist. We recorded responses of phrenic, hypoglossal, and cervical sympathetic nerve activities to progressive hypercapnia after hyperventilation to apnea. Moxonidine (3-100 micrograms/kg i.v.) caused dose-dependent decreases in tonic cervical sympathetic nerve activity and blood pressure, but had no effect on the CO2 threshold (after 30 or 100 micrograms/kg moxonidine, phrenic nerve activity reappeared at 5.8 +/- 0.2% CO2 versus 5.6 +/- 0.3% CO2 in control). Following moxonidine, the slope of the steep portion of the CO2 response tended to increase (10.3 +/- 1.8 versus 7.3 +/- 0.9). Peak phrenic nerve activity was comparable to control at 7.5% CO2 (20 +/- 2 U in control) and at 9.5% CO2 (30 +/- 3 versus 27. +/- 2 U). Similarly, the response of hypoglossal and inspiratory phasic cervical sympathetic nerve activity to a progressive CO2 rise was not affected by moxonidine. By contrast, clonidine in the same doses decreased CO2 sensitivity, because the CO2 threshold was elevated from 5.3 +/- 0.5% to 6.7 +/- 0.4% (p < 0.001). The slope of the CO2 response was decreased from 9.7 +/- 1.9 to 7.4 +/- 1.3 (p = 0.05). Peak phrenic nerve activity was reduced at 7.5% CO2 (11 +/- 5 versus 25 +/- 2 U; p < 0.05) and at 9.5% CO2 (21 +/- 4 versus 33 +/- 2 U; p = 0.06). Clonidine selectively inhibited the response of hypoglossal nerve activity to CO2. The depressive effects of clonidine were reversed by alpha 2-blockade with SK&F-86466 (0.5 or 1 mg/kg). Inspiratory phasic cervical sympathetic nerve activity increased after SK&F-86466 in parallel with phrenic and hypoglossal nerve activity, but the tonic component of cervical sympathetic nerve activity and blood pressure increased only transiently.(ABSTRACT TRUNCATED AT 400 WORDS)

Central effects of 5-HT on respiratory and hypoglossal activities in the adult cat

The activities of the diaphragmatic, internal intercostal and hypoglossal-innervated muscles were studied in adult decerebrate cats in response to 5-HT and related agents (8-OH-DPAT and DOI). The drugs were placed on the floor of the IVth ventricle. The mean respiratory frequency (Fi) increased (124–193% of the control value) within 3 min of the 5-HT application, and decreased thereafter (30–90%). The mean Ti and Te changed similarly, but opposite to Fi. With some delay, the hypoglossal-innervated muscles were tonically activated or exhibited increased activities. Methysergide pretreatment completely blocked the effect of 5-HT on all the respiratory parameters and the hypoglossal-innervated muscles activities. The responses to 8-OH-DPAT and DOI indicate that 5-HT modulates the respiratory frequency via activation of both 5-HT 1A and 5-HT 2 receptors. Nevertheless, the effect of 5-HT on both the expiratory and hypoglossal-innervated muscles seems to depend on 5-HT 2 receptors activation only.

Power spectral analysis of respiratory responses to pharyngeal stimulation in cats: comparisons with eupnoea and gasping.

1. Based on similarities between properties of gasping and the aspiration reflex, we hypothesized that this reflex activates the central pattern generator for gasping. To evaluate this hypothesis, we have analysed high-frequency oscillations in phrenic and hypoglossal neural activities. These oscillations, analysed by power and coherence spectra, are considered as signatures of the central pattern generators for automatic ventilatory activity. 2. In decerebrate, vagotomized, paralysed and ventilated cats, the aspiration reflex was elicited in eupnoea and gasping by mechanical stimulation of the pharynx and electrical stimulation of the glossopharyngeal nerve. 3. Compared with eupnoeic values, the peaks in the power spectra occurred at higher frequencies in spontaneous gasping. Peaks in the coherence spectra showed identical changes. 4. Power and coherence spectra of inspiratory neural activities during the aspiration reflex differed markedly from those of eupnoea, but were similar to those in gasping. 5. We conclude that mechanical stimulation of the pharynx or electrical stimulation of the glossopharyngeal nerve activates a reflex by which the central pattern generator for eupnoea is depressed, and that for gasping is activated. Our results also support the concept that separate brainstem mechanisms generate ventilatory activity in eupnoea and gasping.

Changes in phrenic, hypoglossal and recurrent laryngeal nerve activities after intravenous infusions of aminophylline in cats

Aminophylline is known to have respiratory stimulant properties, and it has been suggested that it may also be effective in sleep apnoea. However, its role in this disorder remains uncertain. Theoretically, increasing upper airway motoneural activity in order to maintain airway patency might alleviate obstructive sleep apnoea. On the other hand, increasing the respiratory drive may also prove beneficial in treating central sleep apnoea. In these studies, we attempted to determine the effect of aminophylline on neural activities of the upper airway and diaphragm. We administered intravenously either a low dose (4 mg.kg-1) or a high dose (16 mg.kg-1) of aminophylline to decerebrated, vagotomized and paralysed cats, and continuously recorded the phrenic hypoglossal and recurrent laryngeal nerve activities for 3 h. Results showed that a high dose of aminophylline induced a marked increase in phrenic nerve activity, but not hypoglossal or recurrent laryngeal nerve activity. In a group treated with a low dosage of aminophylline, a significant increase of activity was found in all three nerves. Furthermore, phrenic nerve activity increased more with a high dose than with a low dose. We confirmed that aminophylline has dose-dependent and selective effects on respiratory neural activity. A low dose acts on the upper airway and diaphragm, but a high dose induces a marked increase in central respiratory drive. According to our results, low dose aminophylline might be beneficial in obstructive sleep apnoea, whereas, a high or low dose might improve some cases of central sleep apnoea.

Postoperative Tracheal Extubation

Postoperative Tracheal Extubation