Respiratory activity in the superior laryngeal nerve of the rabbit

We studied the respiratory modulation of laryngeal afferents and their response to transmural pressure in 24 anesthetized, spontaneously breathing rabbits. Laryngeal afferent activity has a predominant inspiratory augmentation during tracheal breathing or tracheal occlusion that can be accounted for by the respiratory movement transmitted to the larynx through the trachea. During upper airway breathing or upper airway occlusion SLN afferent activity increases in expiration and decreases in inspiration. This respiratory modulation is due to changes in upper airway pressure (Pua). In fact, positive pressure stimulates SLN afferent activity, while negative pressure inhibits it. Mechanical restriction of epiglottal movement reduced the response to Pua changes during upper airway occlusion and application of maintained positive (0.1-0.5 kPa) and negative (-0.1 to -0.5 kPa) pressures (P less than 0.005). Furthermore, surgical removal of epiglottis decreased the baseline activity of SLN to 16.5% of control. These experiments suggest that in the rabbit the epiglottis is the main source of SLN afferent activity and that its displacement, due to changes in Pua, is the most important factor for modulating SLN activity. Most of the laryngeal receptors showed an inspiratory augmentation with tracheal breathing and occlusion, were stimulated by positive pressure and inhibited by negative pressure, reflecting the behavior observed in the whole nerve.     

Respiratory afferent activity in the superior laryngeal nerves

This study evaluates the afferent activity in the superior laryngeal nerve (SLN) during breathing as well as during occluded inspiratory efforts. Experiments were performed in 11 anesthetized and spontaneously breathing dogs. Electroneurographic activity was recorded from the peripheral cut end of the SLN and, in 3 dogs, also from the contralateral vagus nerve. A tracheal cannula with a side arm allowed the bypass of the larynx during breathing and occluded efforts. A clear inspiratory modulation was present in all experimental conditions. Both peak and duration of the SLN activity decreased (87% and 89%) when breathing was diverted from the upper airway to the tracheostomy. Peak and duration of the SLN activity (as % of upper airway breathing) increased during occluded efforts; however, the increase was greater when the larynx was not by-passed (peak = 118% vs 208%, duration = 143% vs 178%). Section of the ipsilateral recurrent laryngeal nerve reduced the inspiratory modulation. Vagal afferent activity increased equally during tracheostomy and upper airway breathing and decreased markedly during tracheal and upper airway occlusions. Our results indicate that collapsing pressure in the larynx is the major stimulus in activating laryngeal afferents.     

The respiratory activity of the superior laryngeal nerve in the rat.

The aim of this study was to characterize the laryngeal afferent activity of the rat. The animals were anesthetized and breathing spontaneously. Laryngeal afferent activity was recorded from both the whole superior laryngeal nerve (SLN) and from single fibers isolated from this nerve. An overall inspiratory augmenting activity was observed in the whole SLN during tracheostomy breathing, tracheal occlusion and upper airway breathing, but an expiratory augmenting activity was present during upper airway occlusion. The inspiratory modulated activity was abolished by bilateral section of the hypoglossal nerves but not the recurrent laryngeal nerves. A great number of receptors (46/80, 58%) were identified as 'drive' receptors, and others as 'pressure' (22/80, 28%) and 'irritant' type receptors (9/80, 11%). Nineteen pressure receptors were stimulated by positive transmural pressure, while only three stimulated by negative pressure. Nine drive receptors were also stimulated by positive pressure and inhibited by negative pressure. Such response to pressure was further evaluated by applying maintained pressures to the functionally isolated upper airway. These results are essentially consistent with findings obtained in the rabbit, but differ from those reported for the dog.     

Sulphur dioxide block of laryngeal receptors in rabbits

In 6 rabbits moving average of activity of superior laryngeal nerve(SLN) increased when pressure in upper airways (Pua) was positive and decreased when it was negative. After SO2 exposure of upper airways SLN activity at Pua = 0 decreased to 40% and was no longer affected by changes in Pua. Activity of 67 fibers of SLN was recorded in 11 rabbits: 35 came from 'pressure' receptors, 27 from 'drive', and 5 from 'flow'. Thirty-three pressure receptors discharged at Pua = 0: 32 increased their firing rate with positive Pua and decreased it with negative Pua, one did the reverse. One pressure receptor silent at Pua = 0 fired with positive Pua, the other with negative Pua. Pressure receptors were slowly adapting. SO2 blocked within 3-9 min 84% of pressure receptors, 56% of drive receptors, and 4 out of 5 flow receptors. The receptors recovered control activity within 5-10 min after SO2 removal. SO2 block of laryngeal receptors may represent a convenient experimental tool for studies of laryngeal reflexes.     

Effect of laryngeal anesthesia on pulmonary function testing in normal subjects

Pulmonary function tests (PFT) were performed on 11 normal subjects before and after topical anesthesia of the larynx. The PFT consisted of flow volume loops and body box determinations of functional residual capacity and airway resistance, each performed in triplicate. After the first set of tests, cotton pledgets soaked in 4% lidocaine were held in the pyriform sinuses for 2 min to block the superior laryngeal nerves. In addition, 1.5 ml of 10% cocaine was dropped on the vocal cords via indirect laryngoscopy. PFT were repeated 5 min after anesthesia. Besides routine analysis of the flow volume loops, areas under the inspiratory (Area I) and expiratory (Area E) portions of the loops were calculated by planimetry. Area I, peak inspiratory flow (PIF), as well as forced inspiratory flow at 25, 50, and 75% forced vital capacity (FVC), decreased after anesthesia. Peak expiratory flow decreased after anesthesia, but Area E and forced expiratory flow at 25, 50, and 75% FVC were unchanged. This protocol also was performed in 12 normal subjects with isotonic saline being substituted for the lidocaine and cocaine. In this group, no significant differences were observed when flow volume loop parameters were compared before and after topical application of saline. In 5 spontaneously breathing anesthetized dogs, posterior cricoarytenoid muscle and afferent superior laryngeal nerve activity were recorded before and after laryngeal anesthesia performed with the same procedure used in the human subjects. Laryngeal anesthesia resulted in a substantial decrease or a complete disappearance of afferent SLN activity recorded during unobstructed and obstructed respiration. The data suggest that laryngeal receptors help modulate upper airway patency in man.     

Reflex effects on breathing of laryngeal denervation, negative pressure and SO2 in upper airways

Respiratory reflex effects of laryngeal denervation, negative pressure and SO2 in upper airways were studied in anesthetized rabbits. Inspiratory efforts with nasal occlusion had longer duration (TIo) and smaller diaphragm activity (Adi) than with tracheal occlusion. After section of superior laryngeal nerves (SLN) these differences disappeared: values with tracheal occlusion became similar to those with nasal occlusion before denervation. This suggests that laryngeal pressure receptors, firing at zero pressure and decreasing their discharge with negative pressures, increase central inspiratory activity. After SO2 TIo, both with tracheal and nasal occlusion, increased even after laryngeal denervation, provided SO2 flowed through nasal pathway. Hence, nose and/or rhinopharynx contain receptors affected by SO2. After laryngeal denervation and SO2 TIo was shorter with nasal than with tracheal occlusion, despite equal Adi. This, combined with the above findings, suggests two groups of pressure receptors in nose and/or rhinopharynx with opposite effects on inspiratory off-switch: one unaffected and the other probably blocked by SO2. During nose breathing section of SLN produced only a slight decrease in mean inspiratory flow.     

Effect of expiratory glottic constriction on lung volume and pattern of breathing in adult dogs

We examined the effect of laryngeal constriction on the pattern of breathing in 4 anaesthetized adult mongrel dogs. By means of a T-shaped tracheostomy tube the larynx could be repeatedly excluded or included in the breathing circuit. Marked expiratory activity of the thyroarytenoid muscle (TA), the main glottic constrictor, was induced by injection of 100-400 ml of air into the pleural space or by inhalation of histamine aerosol (2 dogs) which resulted in rapid shallow breathing. In 21 pairs of runs in the 4 dogs switching from tracheostomy breathing to oral breathing decreased mid-expiratory flow and frequency by 85 +/- 2% (P less than 0.001) and 48 +/- 4% (P less than 0.001), respectively. Although expiratory duration (TE) increased, end-expiratory lung volume also increased by 40 +/- 8 ml or 21 +/- 4% of the tidal volume (VT) during tracheostomy breathing (P less than 0.001). In contrast, VT remained unchanged (P = 0.9). Instantaneous ventilation decreased due to both the prolongation of TE and an increase in inspiratory duration. Our results indicate that laryngeal braking can be recruited in adult dogs and interacts with reflex mechanisms that modulate respiratory timing, thereby significantly influencing end-expiratory lung volume, ventilation and the pattern of breathing. Simulation of the laryngeal mechanism by expiratory resistive loading at the tracheostomy below the larynx points to a non-reflex mechanical effect of the larynx as a resistance in series.     

Laryngeal effects on respiratory pressures and timing in rabbits: role of the vagi

Tidal breathing through a tracheostomy and through the larynx were compared in two groups of rabbits. Ten control and fourteen rabbits with chronically vagally denervated lungs were anaesthetized and spontaneously breathing. Inspiratory and expiratory tracheal pressure and timing components of respiratory pattern were measured in both groups of animals before and after carotid sinus/body denervation and cervical vagotomy. Breathing through the larynx significantly increased the inspiratory pressure and, to a lesser degree, affected expiratory pressure in both groups of animals and changed the respiratory timing by prolongation of TI and shortening of TE. Our results indicate that the larynx prominently influences pressures within the lower respiratory tract but its effect on the pattern of breathing is confined only to animals with an intact lung innervation.     

Ventilation in kittens with chronic section of the superior laryngeal nerves

The breathing pattern of conscious newborn kittens one-to-two weeks old was studied by the barometric method about 5 days after bilateral section of the superior laryngeal nerve (SLN-denervated group) or a sham operation (SLN-sham operated group). None of the ventilatory variables differed between the two groups, whether during normoxia or acute hypoxia (10 min of 10% O2). After anesthesia, delivery of steady airflows in the expiratory direction through the upper airways of the SLN-sham operated had marked inhibitory effects on ventilation which entirely disappeared after SLN section. A small inhibition was still present in the SLN-denervated group, possibly indicating that other non-SLN upper airways receptors developed inhibitory ventilatory effects during the period of chronic denervation. Intermittent expiratory upper airway airflows were much less effective than steady flows and no inhibition was seen with oscillatory flows, indicating that the mode of application of the stimulus to the laryngeal receptors is crucial in determining the magnitude of their reflex response. Under anesthesia, acute bilateral section of the SLN determined a small increase of the integrated peak EMG activity of the diaphragm. We conclude that laryngeal SLN afferents are inhibitory on ventilation in newborn kittens, but this effect is very small during normal conscious conditions. Only under special circumstances, including anesthesia and sustained upper airways flows and pressures, the ventilatory inhibition can be disproportionately magnified.     

Laryngeal receptors and their reflex responses

The afferent activity originating from the larynx shows a considerable respiratory modulation. Receptors responding to pressure changes, inspiratory airflow (cold), and laryngeal movements have been identified. In addition, other receptors without a respiratory modulation are also described. Possible reflex effects of these receptors on breathing pattern, upper airway patency, and defense mechanisms in both adults and newborns are discussed.     

Effects of hypercapnia and hypoxia on laryngeal resistance to airflow.

Ventilation, laryngeal resistance and electromyograms of the diaphragm, posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were recorded in anesthetized, spontaneously breathing cats during 100% O2 administration and during steady state inhalation of hypercapnic and hypoxic gas mixtures. As shown previously, hyperoxic hypercapnia lowered expiratory laryngeal resistance (RlarE). Isocapnic hypoxia also lowered RlarE, and hypercapnia superimposed on hypoxia decreased it further. Hypocapnia raised RlarE. Changes in inspiratory laryngeal resistance (RlarI) were similar to those in RlarE, but smaller. When ventilation was stimulated to the same extent by hypoxia and by hypercapnia, RlarE was lower under hypoxic than hypercapnic conditions in most animals. The electromyograms showed that the respiratory oscillations in laryngeal resistance and the laryngeal responses to hypercapnia and hypoxia were determined chiefly by the activity of the PCA muscle, the abductor of the vocal cords. The TA-a representative adductor muscle-was silent under all conditions studied. The results, considered with previous work, indicate that the larynx plays a part in determining the breathing pattern under resting conditions and during respiratory stimulation by hypercapnia and hypoxia.     

Effects of halothane,enflurane, and isoflurane on laryngeal receptors in dogs

The effects of halothane, enflurane, and isoflurane on laryngeal receptors were investigated in 6 anethetized dogs breathing spontaneously through a tracheostomy. Single unit actiion potentials were recorded from the peripheral cut end of the superior laryngeal nerve (SLN) while different concentrations of volatile anesthetics (1.25, 2.5., 5.0%) were administered in the expiratory direction at a constant air-flow (6 1/min) for 1 min through the functionally isolated upper airway. A total of 21 respiratory-modulated mechanoreceptors, 18 “irritant” receptors, and 7 cold receptors were studied. The overall results obtained from the 16 respiratory-modulated mechanoreceptors challenged with the 3 anesthetic gases disclosed a prevalent inhibitory effect and halothane proved to be the most effective of the 3 gases. The activity during both the inspiratory and expiratory phase was significantly reduced only by halothane (inspiratory phase, P<0.01; expiratory phase, P<0.05), while neither isoflurane nor enflurane caused significant changes in receptor activity. Of the 18 irritant receptors, 14 receptors increased their activity in a dose-related manner in response to one or more of the anesthetics although the effect of halothane was more pronounced than those of enflurane and isoflurane. All of the 7 cold receptos consistently increased their activity in a dose-related manner in response to halothane whereas 3 of 7 receptors were insensitive to enflurane and 4 of 7 receptors were insensitive to isoflurane. Our results indicate that, while all three commonly used anethetics can have an effect on different types of laryngeal receptors, the effects of halothane are more pronounced than those of the other two gases in terms of changes in receptor activity.     

Properties of inspiratory termination by superior laryngeal and vagal stimulation.

Electrical stimulation of two respiratory afferent nerves, the vagus and the internal branch of the superior laryngeal, was used to terminate inspiration. The short latency responses of phrenic motoneurones to these stimuli were studied to determine if inspiratory termination was preceded by a characteristic phrenic motoneurone discharge pattern, reflecting changes in brainstem inspiratory neurone discharge and inspiratory terminating mechanisms. Stimulus trains of sufficient intensity delivered to the superior laryngeal nerve terminated inspiration within 50 ms and were preceded by a stereotyped pattern of phrenic motoneurone discharge. This consisted of a short latency (disynaptic), predominantly contralateral excitation in response to the first shock of the train, followed by a marked and long lasting inhibition. In contrast, vagal stimulation typically terminated inspiration hundreds of milliseconds after the onset of the stimulus train and was not preceded by a stereotyped pattern of phrenic motoneurone responses to single shocks. Transient short latency responses were obtained but were extremely small, requiring considerable excitation followed by a moderate bilateral depression of activity. Inspiration could be terminated with or without the presence of these short latency responses. These results indicate that superior laryngeal and vagal (presumably pulmonary stretch receptor) afferents have different projections to brainstem inspiratory neurones and may exert their effects on inspiratory duration through different, but as yet undefined, neural mechanisms.     

无创正压通气抑制慢性阻塞性肺疾病急性加重期患者吸气肌肉活动的机制

目的探讨无创正压通气（NIPPV）抑制慢性阻塞性肺疾病（COPD）急性发作期患者吸气肌肉活动的机制。方法12例COPD急性加重期患者接受感觉最舒适通气压力水平时的NIPPV,观察患者吸气肌肉用力和呼吸方式的变化。结果与自主呼吸（SB）相比,NIPPV时的潮气量（VT）显著增高（从408ml升到462ml,P〈0.05）;接受NIPPV后VT的增高很迅速,第一呼吸周期时即明显增高。SB时的跨膜压（Pdi）为14.04cmH2O,而NIPPV时为10.98cmH2O,比SB时约减少22%（P〈0.05）。NIPPV时Pdi的下降从第一个呼吸周期即开始,然后进一步迅速下降,治疗至第5个呼吸周期时与SB时相比开始有显著差异（P〈0.05）。SB时的呼吸肌做功（Wp）分别为0.47J/breath和0.95J/L;而NIPPV时分别为0.34J/breath和0.69J/L,比SB时分别减少28%和27%（P〈0.05）。NIPPV时Wp的下降也是从第一个呼吸周期即开始,然后进一步迅速下降,治疗至第5个呼吸周期时与SB时相比开始有显著差异（P〈0.05）。结论本实验证实了NIPPV治疗COPD急性加重期患者时吸气肌肉活动的非化学性抑制作用的存在;这种非化学性抑制作用的产生与NIPPV治疗的开始基本同步,能有效改善患者的呼吸肌肉疲劳。     

The effects of hypercapnia and hypoxia on single hypoglossal nerve fiber activity

The respiratory related modulation of hypoglossal nerve activity has been studied at the single fiber level in cats under hyperoxic hypercapnia and hypoxic conditions and their conduction velocities determined. Changes in fiber activity were compared to simultaneous changes occurring in phrenic activity. Three different kinds of discharge patterns were observed: (a) inspiratory, (b) phasic activity during both inspiration and expiration, and (c) continuous random activity with no respiratory modulation. These fibers could be grouped into three categories according to their pattern of discharge during CO2 breathing. Type I fibers, mean conduction velocity of 30.0 m/sec, exhibited only an inspiratory phasic discharge during 100% O2 breathing. Their discharge frequency increased rapidly with higher levels of CO2 and hypoxia. Type II fibers, mean conduction velocity of 36.7 m/sec, had three different kinds of inspiratory-expiratory discharge patterns during 100% O2 breathing. With increasing hypercapnia or hypoxia fibers of this group discharged phasically during inspiration and discharge at low frequency during expiration. Type III fibers had a non phasic discharge pattern at 100% O2 breathing and at all levels of CO2 tested (up to 10%). Discharge frequency rose during CO2 rebreathing and hypoxia, but the rate of increase was much less than Type I and Type II fibers. Their mean conduction velocity was 41.3 m/sec. The inspiratory activity of Type I and II fibers increased their activity more than the phrenic during hypercapnia and hypoxia. Type II and Type III fibers are responsible at least in part for the tonic activity of the nerve.     

Breathing pattern of neonates during nonnutritive sucking

Alteration of the breathing pattern seen during oral feeding has been attributed to the behavioral activity of sucking, repeated swallowing, and laryngeal chemoreceptor stimulation. Because it preserves the behavioral activity of sucking but eliminates the laryngeal chemoreceptor stimulation and repeated swallowing that occurs during nutritive sucking, the effects of nonnutritive sucking was evaluated in 19 term infants. The suck-pause pattern seen during nonnutritive sucking is similar to that of nutritive sucking. None of the variables measured (inspiratory duration, expiratory duration, breathing frequency, and tidal volume) were significantly altered during the overall period of nonnutritive sucking when compared with previously obtained control values. These results suggest that the alteration of breathing pattern observed during oral feeding cannot be accounted for by the behavioral activity of sucking per se. However, when the sucking phases of the nonnutritive period were compared with the intervening pauses, a reduction in the expiratory duration (P less than 0.05) and a reduction in tidal volume (P less than 0.05) were observed. Thus, the breathing pattern of human neonates is indeed altered during the sucking phase of the nonnutritive period; pressure changes associated with sucking may account for this alteration.     

Alteration in breathing of the awake rat after laryngeal and diaphragmatic muscle paralysis

The respiratory rate (f), tidal volume (VT) and ventilation (V) were measured in 3 groups of rats: 10 rats before and after cutting both recurrent laryngeal nerves (RLNX), 10 rats before and after bilateral phrenicotomy (PNX) and 5 sham transected (SHAMX) rats. All rats were exposed to air and gas mixtures, deficient in O2 and/or enriched with CO2. The barometric method was used to measure ventilatory parameters. The sham operation did not affect breathing pattern or ventilation. In RLNX rats, breathing the various gas mixtures exhibited no changes in V because f uniformly increased as VT declined. Therefore, loss of the neural control of the respiratory functions of the larynx in awake rats exposed to selected gas mixtures has no untoward effects on alveolar ventilation. Changes in ventilation of PNX rats, compared with SHAMX rats, depends on the gas composition breathed. With increasing severity of hypoxia and/or hypercapnia, PNX rats show a marked reduction in alveolar ventilation over that of the SHAMX rats. Thus, when the diaphragm is no longer able to participate in ventilatory responses, gas exchange is likely to become deficient.     

Ventilatory control in patients with hypoxemia due to obstructive lung disease.

In 20 patients with chronic hypoxemia due to chronic obstructive pulmonary disease, we measured responses to CO2 and hypoxia in terms of ventilation and P0.1, the pressure generated by the respiratory muscles during the first 0.1 s of inspiratory effort against a closed airway at functional residual capacity. These responses were compared to those of a control group of 17 patients with similar ventilatory abnormality but without hypoxemia. Hypoxemic patients demonstrated significantly less response to hypoxia than did control subjects in terms of both ventilation and P0.1 The decreased hypoxic response might be analogous to that reported in high altitude dwellers and patients with cyanotic congenital heart disease. Ventilatory responses to CO2 were depressed in hypoxemic patients, but P0.1 responses were not significantly decreased. While breathing at rest with arterial O2 saturation of 95 per cent, hypoxemic patients demonstrated the same minute ventilation as control subjects, but tidal volume was smaller, inspiratory duration was shorter, and breathing frequency was slightly higher. This breathing pattern appeared to be independent of whether or not these patients retained CO2.     

Hypoglossal motoneuron responses to pulmonary and superior laryngeal afferent inputs

In decerebrate, paralyzed cats ventilated with a cycle-triggered pump, the inspiratory discharges of the hypoglossal (whole nerve or single fibers), phrenic, and recurrent laryngeal nerves were compared, and the effects of pulmonary and superior laryngeal afferent inputs were observed. During lung inflations in phase with neural inspiration, hypoglossal and recurrent laryngeal activities differed from phrenic with respect to (a) burst onset times: both preceded the phrenic; (b) overall pattern: phrenic, augmenting; hypoglossal, decrementing; recurrent laryngeal, plateau-like. When inflation was withheld, the phrenic pattern was not markedly changed, but both hypoglossal and recurrent laryngeal became augmenting; the marked increase of hypoglossal activity (both whole nerve and single fiber) indicated strong inhibition by lung afferents. Superior laryngeal electrical stimulation evoked excitation of the contralateral phrenic (latency 4.1 msec) and the ipsilateral whole hypoglossal (latency 5.3 msec), followed by bilateral inhibitions (durations 20-30 msec); most hypoglossal fibers showed only inhibition. We conclude that, although both hypoglossal and phrenic outputs are driven by the inspiratory pattern generator(s), their promotor systems differ with respect to influences from central and peripheral inputs.     

Respiratory resetting induced by activation of inspiratory bulbo-spinal neurons

The respiratory effects elicited by spinal (C2-C3) stimulation at the level of descending inspiratory axons were studied in paralysed, non-vagotomized and artificially ventilated cats anaesthetized with urethane-chloralose. The activation of inspiratory bulbospinal axons in the ventrolateral quadrant was confirmed by recording the ipsilateral phrenic excitation following a single pulse. Brief stimulus trains delivered at the same locus during expiration elicited short- and long-term phrenic activations. The short-term activation consisted of a tetanic orthodromic response. The long-term activation, of central origin, exhibited the same pattern as a spontaneous inspiration and consisted of an inspiratory resetting which necessitated weak anaesthesia and light hypocapnia. Control experiments (restricted lesions of the medulla and the cervical cord, recording of afferent activity in thalamic sensory nuclei, medullary stimulation) revealed that this inspiratory resetting could not be related to appreciable activation of either non-respiratory efferents or spinal afferent pathways studied but was likely to depend on the activation of the descending inspiratory axons. We conclude that the respiratory resetting obtained by spinal stimulation resulted from mass antidromic activation of the inspiratory bulbospinal neurons which thus appear to be involved in the generation of the respiratory rhythm.