Studies on laryngeal calibre during stimulation of peripheral and central chemoreceptors, pneumothorax and increased respiratory loads

1. The effects of asphyxia, hypoxia, hypercapnia, stimulation of peripheral chemoreceptors, pneumothorax and breathing through resistances have been investigated on laryngeal resistance to airflow in anaesthetized cats, with and without bilateral vagotomy below the origin of the recurrent laryngeal nerves.2. Resistance to airflow of the innervated larynx was usually measured with the larynx isolated in situ with constant flow from the trachea to a pharyngeal opening, and expressed by the relationship between translaryngeal pressure and airflow.3. Asphyxia, hypoxia and hypercapnia each stimulated breathing and decreased laryngeal resistance to airflow, in both the inspiratory and expiratory phases. After vagotomy the effect was reduced, abolished or (usually) reversed to a laryngeal constriction, especially in expiration.4. Intra-arterial injections of potassium cyanide (to stimulate carotid body chemoreceptors) caused a short apnoea or an augmented breath followed by hyperpnoea, concurrently with expiratory constrictions of the larynx. The responses were usually stronger after bilateral vagotomy.5. Pneumothorax caused tachypnoea, inspiratory dilatations and expiratory constrictions of the larynx. The responses were abolished by vagotomy.6. Imposition of respiratory resistances dilated the larynx, in inspiration and expiration, while complete closure of trachea caused expiratory constrictions of the larynx. These changes did not depend on intact vagal pathways.7. The results are discussed in terms of nervous control of the larynx in the different conditions.     

The effects of lung reflexes on laryngeal resistance and motoneurone discharge

1. The reflex action of stimulation of alveolar J-receptors and of airway epithelial irritant receptors has been investigated on laryngeal resistance to airflow and on laryngeal motoneurone discharge in cats and rabbits.2. Resistance to airflow of the innervated larynx was measured (1) with the larynx isolated in situ with constant flow from the trachea to a pharyngeal opening; and (2) with the animal breathing through the larynx and the pharyngeal opening. With both methods resistance was determined from the relationship between translaryngeal pressure and airflow.3. In control conditions the laryngeal resistance was about one tenth of total lung resistance.4. I.V. injections of phenyl diguanide (to stimulate J-receptors) caused apnoea and complete closure of the larynx, followed by rapid shallow breathing with expiratory constrictions of the larynx. Expiratory laryngeal motoneurones were strongly stimulated.5. The laryngeal responses to phenyl diguanide were nearly abolished by bilateral vagotomy in the chest (below the origin of the recurrent laryngeal nerves), and were absent on injection of the drug into the left atrium; the motoneurone responses were abolished by vagotomy and lessened by paralysis and artificial ventilation.6. I.V. injections of histamine acid phosphate or inhalation of an aerosol of the drug in solution (to stimulate lung irritant receptors) caused tachypnoea and expiratory constrictions of the larynx, and increased discharges in expiratory laryngeal motoneurones.7. The laryngeal responses to histamine were more than halved by bilateral intrathoracic vagotomy.8. Phenyl diguanide and histamine increased the frequency of the discharge of inspiratory laryngeal motoneurones, but reduced the number of impulses per inspiratory phase. Laryngeal resistance in inspiration was usually increased.     

The responses of superior laryngeal nerve afferent fibres to laryngeal airway CO2 concentration in the anaesthetized cat

In anaesthetized cats, the isolated, in situ, larynx was subjected to a simulated respiratory cycle and the responses of fifty-six superior laryngeal nerve (SLN) afferent fibres to respiration-related stimuli were examined during changes in the fractional CO2 concentration of the laryngeal airway (Faw, CO2). Sensory SLN fibres which displayed low rates of discharge when the larynx was unventilated (quiescent fibres) and which responded to negative laryngeal airway pressure were excited by elevations in Faw, CO2 whereas quiescent fibres responsive to positive laryngeal pressure were inhibited by the same procedure. We propose that changes in airway CO2 levels may play a role in maintaining upper airway patency, especially during sleep.     

The effects of changes in laryngeal airway CO2 concentration on genioglossus muscle activity in the anaesthetized cat

In the anaesthetized cat the larynx was isolated in situ, artificially ventilated and used to assess reflex effects exerted by respiration-related laryngeal stimuli on genioglossus electromyographic activity (Gg EMG) and respiratory frequency (RF). Phasic Gg EMG was not observed when the larynx was unventilated but was evoked, with a concurrent decrease in RF, when negative pressures or oscillatory pressures similar to those of normal ventilation were applied to the larynx. Increases in laryngeal airway CO2 concentration also enhanced Gg EMG and reduced RF. All reflex effects were abolished by bilateral section of the superior laryngeal nerves. We propose that negative intralaryngeal pressure and CO2 may act together to restore pharyngeal patency during obstructive apnoea.     

Reflex effects of laryngeal irritation on the pattern of breathing and total lung resistance

1. The reflex responses to chemical and mechanical irritation of the laryngeal mucosa have been studied by applying stimuli to the open larynx of tracheostomized cats while monitoring ventilatory and circulatory variables. The responses were studied before and after vagotomy and before and after denervation of the larynx by transection of the superior and recurrent laryngeal nerves.

2. The immediate response to laryngeal irritation was not consistent. The most frequent responses were coughing, and slowing and deepening of breathing without coughing. Less common were expiratory apnoea and sustained, simultaneous inspiratory and expiratory activity.

3. A consistent late change in the pattern of breathing occurred. Slower, deeper breathing with increased total lung resistance (bronchoconstriction) was seen after the immediate response abated.

4. The slowing of breathing was due to prolongation of both the time for inspiration and the time for expiration. The rate of increase in phrenic nerve activity was also slowed.

5. Vagotomy did not alter qualitatively the reflex changes in the pattern of breathing, although bronchoconstriction no longer occurred.

6. The responses were abolished by denervation of the larynx.

     

The cholinergic pathway to cerebral blood vessels

Summary The effect of stimulating the greater superficial petrosal nerve (g.s.p.n.) upon retroglenoid venous blood flow has been tested in anaesthetized, paralysed and artificially ventilated rats. In 11 out of 15 tests, blood flow increased by an average of 25% with a time to peak response of 28 s. This response was abolished with the injection of atropine 0.1 mg kg^–1 injected intra-arterially. With both petrosal nerves intact, the administration of 6–7% CO₂ in air or 15% O₂ in N₂ caused average increases in blood flow of 105% and 45% respectively. These responses were not affected by bilateral section of the g.s.p.n. Similar experiments were carried out in 5 anaesthetized, spontaneously breathing rabbits in which, in addition toPaCO₂ andPaO₂,PO₂,PCO₂ and blood flow in the caudate nucleus were measured continuously using chronically implanted mass spectrometer catheters and heated thermistors. Caudate nucleus blood flow increased in response to hypoxia and hypercapnia and this response was not significantly affected by section of one or both g.s.p.n., sinus or vagus nerves. With section of sinus and vagus nerves, blood flow changed passively with arterial pressure.     

The reflex effects of intralaryngeal carbon dioxide on the pattern of breathing

1. The reflex effects on the pattern of breathing and total lung resistance of introducing 30, 10 and 5% CO(2) in air into the larynx have been studied in anaesthetized and decerebrate cats breathing through a tracheostomy tube.2. Flowing 30% CO(2) into the larynx caused a two-phased response. First, respiratory frequency and tidal volume decreased, with a consequent fall in minute ventilation. After two to ten breaths, frequency remained slow, but tidal volume increased beyond the control level, so that minute ventilation was restored to control levels.3. Flowing 5 or 10% CO(2) into the larynx caused slowing of breathing with small and inconsistent changes in tidal volume. Minute ventilation was significantly diminished.4. Off effects, on re-introducing air into the larynx, after 2 and 10 min of CO(2) exposure, suggested that the reflex response diminishes with increased duration of exposure to CO(2).5. None of the concentrations of intralaryngeal CO(2) changed total lung resistance or compliance.6. CO(2) mixtures in the larynx generally caused no change in blood pressure or pulse rate of the cats.7. The reflex effects of intralaryngeal CO(2) were abolished by denervating the larynx.8. Hypoxic mixtures introduced into the larynx did not change breathing.     

The influence on the breathing pattern in man of moderate levels of continuous positive and negative airway pressure and of positive end-expiratory pressure during air and CO2 inhalation

The purpose of this study was to determine in man the effect on the breathing pattern of continuous positive (CPAP), continuous negative (CNAP) and positive end-expiratory (PEEP) airway pressure during air breathing and CO₂ inhalation. Six subjects were exposed to CPAP, CNAP and PEEP 0.5 kPa, while five subjects were exposed to CPAP and CNAP 0.8 kPa. End-expiratory lung volume increased during CPAP 0.8 kPa and decreased during CNAP 0.8 kPa. CPAP induced more extensive changes in the ventilatory pattern, and the changes in each parameter were larger than observed during CNAP and PEEP at the same pressure level. In contrast to previous reports we found the effect of CO₂ inhalation combined with the effect of pressure breathing to be not stronger than additive. Even moderate CPAP induced alveolar hyperventilation with marked reduction in arterial PCO₂ (PaCO₂) when breathing air. With increasing fraction of CO₂ in the inspiratory gas, the difference in PaCO₂ between CPAP and no CPAP disappeared. PEEP also affected the breathing pattern in that it induced an increase in mean inspiratory flow and mean expiratory flow and a reduction in inspiratory duration. Occurrence of ventilatory pauses depended on whether mouthpiece or facemask was used. CPAP and CNAP did not influence the occurrence of pauses, while PEEP prolonged post-expiratory pauses. We conclude that CPAP, CNAP and PEEP induce active ventilatory responses in man and that strong mechanisms are involved during CPAP since PaCO₂ is markedly reduced.     

The effects of hypoxia and CO2 on the sleep-waking pattern of the potoroo (Potorous tridactylus apicalis)

Four male potoroos (Potorous tridactylus apicalis) breathed 21% and 7% O₂ with and without the addition of 5% CO₂. The effects of these gas mixtures on the potoroo's sleeping-waking pattern (SWP) were studied. The SWP while breathing 21% O₂/5%CO₂ was unchanged when compared with that of breathing ambient air (21% O₂). While breathing 7% O₂, the SWP was severely disrupted: total sleep time (TST) and slow wave sleep (SWS) increased markedly. Brain temperature fell substantially. Paradoxical sleep (PS) was almost abolished and wakefulness (W) decreased. The addition of 5% CO₂ to the O₂ deficient gas mixture, i.e., 7% O₂/5% CO₂, restored the SWP to that obtained while breathing ambient air. It is concluded that CO₂ neutralizes the disruptive effect which hypoxia has on the potoroo's SWP. It is hypothesized that this constitutes a homeostatic mechanism for stabilizing the SWP and is carried over from pouch life.