Walter M. St. John

Afferent pathways for hypoglossal and phrenic responses to changes in upper airway pressure

Our purpose was to determine the afferent pathways underlying reflexes by which changes in upper airway pressure induced alterations in hypoglossal and phrenic nerve activities. An isolated upper airway was produced in decerebrate, vagotomized, paralyzed and ventilated cats. Efferent activities of the phrenic and hypoglossal nerves were monitored. Hypoglossal activity significantly increased following pressure changes in the upper airway of -4 to -21 cm H2O; phrenic discharge declined in most trials. Similar alterations of neural activities were induced by positive pressures though changes of +14 to +21 cm H2O were required for significant responses. These changes in hypoglossal and phrenic activities were greatly reduced following bilateral sectionings of the superior laryngeal nerves but were augmented after the pharyngeal branches of the glossopharyngeal nerves were sectioned. Additional bilateral destruction of the trigeminal nerves almost entirely eliminated responses to pressure changes. We conclude that upper airway receptors may serve to maintain patency of the upper airways. These receptors may play a crucial role in promoting release from upper airway obstructions, especially in sleep.

Receptors responding to changes in upper airway pressure

Our purpose was to characterize receptors which respond to changes in upper airway pressures. Such changes cause alterations in hypoglossal and phrenic nerve activities. Decerebrate, vagotomized, paralyzed and ventilated cats were prepared so that pressures could be altered within segments of upper airways. Activities of single fibers in the superior laryngeal and glossopharyngeal nerves were monitored. Most superior laryngeal receptors discharged tonically at zero transmural pressure. Discharges of approximately half decreased (A) and the rest increased (B) with pressure reductions of -7 to -28 cm H2O. Pressure increases of +7 to +28 cm H2O caused increases in Group A activities while Group B responses varied. The remaining receptors were silent, being activated by pressure decreases and/or increases. Activities of other silent receptors, similarly activated, were recorded from glossopharyngeal nerve. Tonically active glossopharyngeal receptors increased discharge after both pressure increases and decreases. Most tonically active and silent receptors, having afferents in either nerve, adapted incompletely to sustained pressures. These may have major functions in hypoglossal responses to changes in upper airway pressures.

Medullary axonal projetions of respiratory neurons of pontile pneumotaxic center

In decerebrate, cerebellectomized, vagotomized, paralyzed and ventilated cats, activities were recorded from the phrenic nerve and single respiratory neurons in the area of the nucleus parabrachialis medialis and Kölliker-Fuse nucleus. Stimuli were delivered in the medulla and cervical spinal cord to elicit antidromic action potentials for these neurons and, hence, establish their axonal projections. Antidromic activation was obtained for 18 of 193 neurons following medullary stimulations. Following spinal stimulations, only two respiratory neurons exhibited some responses characteristic of antidromic activation. In the same pontile areas, a number of neurons with no respiratory-modulated or spontaneous activities were antidromically activated by medullary or spinal stimulations. Results are considered in the context of neuroanatomical studies which have established possible interconnections within the brainstem respiratory control system, and hypotheses for functions of the pontile pneumotaxic center in ventilatory control.

Responses of respiratory modulated and tonic units in the retrotrapezoid nucleus to CO2.

We hypothesized that the retrotrapezoid nucleus (RTN) contains both respiratory modulated (RM) and non-respiratory modulated (NRM) neurons which participate in the ventilatory response to increased CO2. We made extracellular recordings of the activity of 46 single units in the RTN of 9 decerebrate, paralyzed, ventilated cats (5 intact; 4 with carotid body and sinus ablation) under eucapnic (PCO2 = 34.2 +/- 3.5 mmHg; mean +/- SD) and hypercapnic (PCO2 = 47.4 +/- 3.4 conditions. To define a RM unit, we used the eta 2 statistic which is the ratio of the variance of the unit firing rate within respiratory cycles to that across respiratory cycles. We classified the units as RM (N = 17) if the eta 2 values in eucapnia or hypercapnia were > or = 0.25 and as NRM (N = 29) if the values were < 0.25. Overall, 19/46 units (41%) increased their firing rate with increased CO2, 5 decreased their firing rate, and 22 had no significant change in firing rate. Of 17 RM units, 8 (47%) increased their mean firing rate with hypercapnia from 7.6 +/- 3.9 to 23.2 +/- 6.8 spikes/sec. These included 5 inspiratory units, 2 inspiratory units that had an onset of firing in late expiration (Pre-I/I), and 1 expiratory unit. Seven of these also changed their discharge pattern (eucapnic eta 2 = 0.02 to 0.12; hypercapnic eta 2 = 0.34 to 0.79) Of 29 NRM units, 11 (38%) showed a significant increase in mean firing rate with CO2 stimulation from 19.8 +/- 7.2 to 31.3 +/- 8.2 spikes/sec. The RTN has RM units which change their discharge pattern and firing rate in response to increased CO2, as do units within the medulla and pons, and it has NRM units which are also responsive to increased CO2. These data indicate that some neurons of the RTN are involved in the central chemoreceptor response but they provide no direct evidence that chemoreception resides within the RTN.

Differential alteration by hypercapnia and hypoxia of the apneustic respiratory pattern in decerebrate cats.

1. A combination of bilateral lesions within the nucleus parabrachialis medialis complex (n.p.b.m.) and bilateral vagotomy typically resulted in an apneustic respiratory pattern in decerebrate and paralysed cats. Integrated efferent phrenic nerve activity was recorded as an index of the respiratory rhythm.

Comparison of respiratory-related trigeminal, hypoglossal and phrenic activities.

In decerebrate, paralyzed and vagotomized cats, we recorded activities of hypoglossal and phrenic nerves and of the mylohyoid branch of the trigeminal nerve. At normocapnia, a respiratory-modulated trigeminal discharge could be discerned in most cats. This discharge was characterized by a diminution of activity during neural inspiration and a peak in expiration. In hypercapnia or hypoxia, peak activity increased and its time of occurrence moved to late inspiration. Augmentations of peak trigeminal, hypoglossal and phrenic activities were proportional. Peak trigeminal and hypoglossal activities increased more than phrenic following administrations of protriptyline, strychnine and, in some cats, cyanide or doxapram. Peak trigeminal activity fell more than phrenic after diazepam. Pentobarbital or halothane reduced peak hypoglossal, but not trigeminal, activity more than phrenic. However, after these anesthetics, trigeminal activity became restricted to the inspiratory-expiratory junction. We conclude that trigeminal and hypoglossal activities are more dependent upon processes within the reticular formation than is the bulbospinal-phrenic system. Central and peripheral chemoreceptor influences are distributed equivalently upon trigeminal, hypoglossal and phrenic motoneurons.

Influence of reticular mechanisms upon hypoglossal, trigeminal and phrenic activiteis

Abstract Studies were undertaken to evaluate the hypothesis that mechanims within the reticular formation influence activities of nerves to muscles of the upper airways more than the bulbospina-phrenic system. In decerebrate, vagotomized, paralyzed and ventilated cats, activities of the phrenic, trigeminal, and the hypoglossal nerves were monitores. Activity of the pontile and medullary reticular formation was increased directly by electrical stimulation within the brainstem and indirectly by stimulating the sciatic nerve. Trigeminal and hypoglossal discharges increased more than phrenic during stimulating at many brainstem loci. Changes were typically maintained for one or more respiratory cycles following termination of stimulation. At some loci, activation of neurons by microinjections of glutamate increased trigeminal and hypoglossal activities more than phrenic. Although responses were extremely variable, activities of the trigeminal and/or hypoglossal nerves usually increased more than phrenic during stimulations of the sciatic nerve or upon termination of stimulation. The result support the conclusion that respiratory-modulated trigeminal and hypopglossal discharges are dependent upon reticular mechanimss for their expression.

Alterations of hypoglossal motoneuronal activities during pulmonary inflations

Preventing pulmonary inflation during inspiration results in greater augmentations in activity of the hypoglossal nerve than in the phrenic nerve. Our purpose was to characterize the hypoglossal motoneuronal activities which underlie these augmentations. Activities of the phrenic and hypoglossal nerves and single hypoglossal fibers were recorded in decerebrate and paralyzed cats. Ventilation was by a servo-respirator which produced changes in lung volume in parallel with phrenic activity. The number of motoneurons that discharged during cycles in which the lungs were inflated increased with elevations of end-tidal fractional concentrations of CO2 (FETCO2) from 0.05 to 0.06 and 0.09. At each FETCO2, the discharge frequency increased when pulmonary inflation was withheld. In addition, withholding inflation resulted in the recruitment of other motoneuronal activities. Most motoneurons discharged during the period of the phrenic burst (inspiratory neurons). Lesser numbers of inspiratory-expiratory, expiratory-inspiratory, and tonic motoneuronal activities were also recorded. Results are considered in the context of the inhibition of respiratory motoneuronal activity by vagal pulmonary afferent fibers. The possible role of such inhibition, and release from this inhibition, in maintenance of patency of the upper airways is discussed.

Characterization of respiratory-related activity of the facial nerve

Activities of the facial, hypoglossal and phrenic nerves were recorded in decerebrate and paralyzed cats. These animals were ventilated with a servo-respirator which produced lung inflations in parallel with phrenic activity. Peak inspiratory phrenic, hypoglossal and facial activities increased in hypercapnia or hypoxia. When pulmonary inflation was prevented, hypoglossal and facial activities increased more than phrenic. Responses to withholding lung inflation differed from those following vagotomy. These differences were observed in expiratory facial and hypoglossal activities and in hypercapnia- and hypoxia-induced changes in facial activity. Administration of pentobarbital or hyperventilation to hypocapnia caused greater suppressions of hypoglossal than facial activity; the latter declined more than phrenic activity. The results support the hypothesis that influences from the brainstem reticular formation and from pulmonary stretch receptors are differentially distributed to motoneurons innervating upper airway muscles compared to those of the bulbospinal-phrenic system. The concept that ventilatory activity is influenced by tonic, as well as phasic discharge of pulmonary receptors is discussed.

Activity of abdominal muscle motoneurons during hypercapnia

Our purpose was to examine the influence of hypercapnia on the activity of motoneurons innervating the transversus abdominis and internal oblique abdominal muscles, and of integrated phrenic and abdominal motor nerve activities. Studies were done in nine adult cats that were decerebrated, vagotomized, thoracotomized, paralyzed and ventilated mechanically. Of 42 motoneurons examined, 24 showed strong respiratory modulation (RM neurons), with the discharge confined primarily to the central expiratory period. The remaining 18 motoneurons discharged tonically, and failed to show respiratory modulation even at increased levels of central respiratory drive. Hyperoxic hypercapnia augmented the activities of the phrenic and abdominal nerves and increased the early expiratory discharge frequency of the RM neurons. The hypercapnia-induced increase in firing frequency during early expiration was accompanied by a corresponding decline in late expiration, and a virtual abolition of the inspiratory activity in the few neurons that discharged in this phase under normocapnic conditions. Finally, hypercapnia induced an increase in the number of spikes generated during each expiratory period in about half of the RM neurons, whereas the remaining cells showed a decrease. Thus, the increased peak activity of the integrated whole abdominal nerve burst with hypercapnia was brought about by a shift in the temporal pattern of motoneuron firing, or by an increase in the number of spikes generated during the expiratory period. The steep rate of rise and the pronounced early expiratory peak observed in the integrated abdominal nerve burst during hypercapnia in this preparation are consistent with the increase in motoneuron firing frequency during the early stages of the expiratory phase.