Ronan G. O'Regan

Reflex respiratory response to changes in upper airway pressure in the anaesthetized rat

1 We examined the upper airway (UA) motor response to upper airway negative pressure (UANP) in the rat. We hypothesized that this response is mediated by superior laryngeal nerve (SLN) afferents and is not confined to airway dilator muscles but also involves an increase in motor drive to tongue retractor and pharyngeal constrictor muscles, reflecting a role for these muscles in stabilizing the UA. 2 Experiments were performed in 49 chloralose‐anaesthetized, tracheostomized rats. Subatmospheric pressure in the range 0 to −30 cmH2O was applied to the isolated UA. Motor activity was recorded in separate experiments from the main trunk of the hypoglossal nerve (XII, n= 8), the pharyngeal branch of the glossopharyngeal nerve (n= 8), the medial and lateral branches of the XII (n= 8) and the pharyngeal branch of the vagus (n= 8). Afferent activity was recorded from the whole SLN in six experiments. 3 All UA motor outflows exhibited phasic inspiratory activity and this was significantly (P < 0.05) increased by UANP. Tonic end‐expiratory activity increased significantly in response to pressures more negative than −20 cmH2O. Bilateral section of the SLN also increased (P < 0.05) motor activity and abolished the responses to UANP. Electrical stimulation of the SLN inhibited inspiratory XII activity. SLN afferents were tonically active and inhibited by UANP. 4 We conclude that UANP causes a reflex increase in motor drive to pharyngeal dilator, tongue retractor and pharyngeal constrictor muscles via afferent fibres in the SLN. Tonic activity in SLN afferent fibres at zero transmural pressure exerts a marked inhibitory effect on UA motor outflow.

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.

Carbon dioxide‐sensitive superior laryngeal nerve afferents in the anaesthetized cat

The effects of CO2 on laryngeal receptors were studied in ten anaesthetized, paralysed, artificially ventilated cats using a preparation in which the upper airway was isolated in situ and artificially ventilated. This allowed CO2 to be confined to the upper airway and enabled responses to CO2 to be recorded whilst the larynx was being ventilated under physiological conditions. Single‐unit afferent activity was recorded from the superior laryngeal nerve and the pressure and thermal sensitivity of receptors determined. Carbon dioxide responses were tested by switching from upper airway ventilation with room air to mixtures containing 5 and 9% CO2 with 21% O2 in N2. Fibres were classified into two broad groups, tonic and quiescent, depending on their level of activity when the larynx was not being ventilated. All tonic fibres responded to either positive or negative pressure. Quiescent fibres were either positive or negative pressure receptors, cold receptors or had no response to pressure or cold airflow. The majority of all categories of fibres were significantly affected by CO2 in a reversible and usually concentration‐dependent manner. Tonic fibres were inhibited, regardless of pressure sensitivity. Quiescent negative and positive pressure receptors were excited and inhibited respectively whilst cold receptors and fibres with no response to occlusion were excited. Laryngeal hypoxia and systemic asphyxia and hypercapnia had no effect on receptor activity. We conclude that the majority of laryngeal receptors are sensitive to CO2 and that this receptivity may be important in the control of ventilation and upper airway muscle activity.

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.

Intralaryngeal neuroanatomy of the recurrent laryngeal nerve of the rabbit.

We undertook this study to determine the detailed neuroanatomy of the terminal branches of the recurrent laryngeal nerve (RLN) in the rabbit to facilitate future neurophysiological recordings from identified branches of this nerve. The whole larynx was isolated post mortem in 17 adult New Zealand White rabbits and prepared using a modified Sihlers technique, which stains axons and renders other tissues transparent so that nerve branches can be seen in whole mount preparations. Of the 34 hemi‐laryngeal preparations processed, 28 stained well and these were dissected and used to characterize the neuroanatomy of the RLN. In most cases (23/28) the posterior cricoarytenoid muscle (PCA) was supplied by a single branch arising from the RLN, though in five PCA specimens there were two or three separate branches to the PCA. The interarytenoid muscle (IA) was supplied by two parallel filaments arising from the main trunk of the RLN rostral to the branch(es) to the PCA. The lateral cricoarytenoid muscle (LCA) commonly received innervation from two fine twigs branching from the RLN main trunk and travelling laterally towards the LCA. The remaining fibres of the RLN innervated the thyroarytenoid muscle (TA) and comprised two distinct branches, one supplying the pars vocalis and the other branching extensively to supply the remainder of the TA. No communicating anastomosis between the RLN and superior laryngeal nerve within the larynx was found. Our results suggest it is feasible to make electrophysiological recordings from identified terminal branches of the RLN supplying laryngeal adductor muscles separate from the branch or branches to the PCA. However, the very small size of the motor nerves to the IA and LCA suggests that it would be very difficult to record selectively from the nerve supply to individual laryngeal adductor muscles.

The effects of oesophageal distension on diaphragm and laryngeal muscle activity in the anaesthetized cat.

The electromyographic (EMG) activities of diaphragm and laryngeal muscles were recorded during oesophageal distension in anesthetized cats. The responses to distension of the thoracic oesophagus differed from those evoked by distension of the cervical oesophagus. The crural component of the diaphragm (CD) was inhibited by distension of the thoracic oesophagus; distension of the cervical oesophagus did not affect CD EMG. Thyroarytenoid (TA) muscle EMG increased markedly and consistently in response to distension of the cervical oesophagus. Distension of the thoracic oesophagus only produced statistically significant increases in TA EMG with high distending volume (10 ml) at the level of the gastro‐oesophageal junction. The main abductor of the vocal cords, the posterior cricoarytenoid (PCA) was either unchanged or decreased by oesophageal distension. The electrical activities of left paratendinous diaphragm, left costal diaphragm, internal intercostal and external intercostal muscles remained unchanged. The entire pattern would appear to constitute a means to aid passage of a bolus into the stomach, and simultaneously guard the respiratory tract from reflux or aspiration.

Potassium and ventilation during exercise above and below the ventilatory threshold.

Increases in arterial plasma potassium during exercise may provide an important drive to ventilation. We examined the changes in arterialized venous plasma potassium concentration ([K +]av) and ventilation that occur during sustained exercise at workloads above and below the ventilatory threshold (Vt) in young health humans. After the onset of exercise at a workload below-Vt, [K +]av rose by 0.3 (+/- 0.1) mmol l-1 (mean +/- SEM). Following 30 min of exercise at this intensity [K +]av had fallen (P < 0.05, ANOVA) by an amount approximately equal to one third of the initial increase. While [K +]av fell, ventilation remained stable. At 5 min after the onset of sustained exercise above the Vt [K +]av had risen by 0.7 (+/- 0.1) mmol l-1 and thereafter remained constant. Ventilation slowly increased throughout the above-Vt protocol. These results show significant differences in the time course of the changes in [K +]av and ventilation. They do not support the hypothesis that changes in [K +]a during moderate exercise cause linearly related changes in ventilation.

The Effects of Airway CO2 on Laryngeal Pressure, ‘Drive’ and Cold Receptors in Spontaneously Breathing Cats

We have previously demonstrated that the activity of superior laryngeal nerve afferents is affected when CO2 is applied continuously to the laryngeal lumen using an isolated, artificially ventilated upper airway (UA) preparation in anaesthetized, paralysed cats (Bradford, et al., 1990a).

International Meetings on Arterial Chemoreceptors: Historical Perspectives

The progression of knowledge in a field of scientific research can be aptly chronicled by a study of the records of scientific meetings on that topic. This review describes the highlights of the first 8 international meetings on arterial chemoreception, and as such provides an interesting historical view of the developments in carotid body research since the 1950’s. The success of these meetings culminated in the formation of the International Society for Arterial Chemoreception (ISAC) in 1988. This marked the beginning of a new era with more frequent meetings held within a formal international organizational structure. Four meetings have been held under the auspices of the Society, including the 12th International meeting held in Dublin in September 1993, the proceedings of which form this volume. These meetings are such recent events, and included such a large volume of scientific work, that it would be impossible to accurately describe their place in the history of chemoreceptor research. For this reason, this chapter concentrates largely on the earlier meetings. There is a danger that a review such as this could become a mere catalogue of brief abstracts. Therefore, the focus of this chapter has been further narrowed so that particular attention is paid to work which was the source of controversy or papers which opened new horizons in chemoreceptor research. As a consequence, many excellent experiments and experimenters are not mentioned. We hope, however, that this description of the importance of scientific meetings in the development of carotid body research, while mentioning relatively few individuals, will be taken as a tribute to all those who have participated in such meetings over the years.