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Biomedical subjects

W M St John

Publications and source records attributed to W M St John.

At least 19 recordsLinked to original sources

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.

Abdominal Muscles

Reductions of neural activities to upper airway muscles after elevations in static lung volume.

We evaluated the hypothesis that the tonic discharge of pulmonary stretch receptors significantly influences the respiratory-modulated activities of cranial nerves. Decerebrate and paralyzed cats were ventilated with a servo-respirator, which produced changes in lung volume in parallel with integrated phrenic activity. Activities of the facial, hypoglossal, and recurrent laryngeal nerves and nerves to the thyroarytenoid muscle and triangularis sterni were recorded. After a stereotyped pattern of lung inflation, tracheal pressure was held at 1, 2, 4, or 6 cmH2O during the subsequent ventilatory cycle. Increases in tracheal pressure caused progressive reductions in both inspiratory and expiratory cranial nerve activities and progressive elevations in triangularis sterni discharge; peak levels of phrenic activity declined modestly. Similar changes were observed in normocapnia and hypercapnia. We conclude that the tonic discharge of pulmonary stretch receptors is an important determinant of the presence and magnitude of respiratory-modulated cranial nerve activity. This reflex mechanism may maintain upper airway patency and also regulate expiratory airflow.

Anesthesia

Vestibular and cerebellar modulation of expiratory motor activities in the cat.

1. The purpose of our investigation was to evaluate the hypothesis that components of the vestibular and cerebellar systems regulate efferent respiratory-modulated activities of cranial and spinal nerves. The hypothesis was based upon the observation that spinal neural activities during expiration are greatly altered subsequent to a change in posture. 2. In decerebrate and paralysed cats, efferent activities were recorded from the central cut ends of the phrenic nerve, intercostal nerve, branch of the intercostal nerve innervating the triangularis sterni, cranial iliohypogastric (abdominal) nerve and recurrent laryngeal nerve. 3. Animals were artificially ventilated. Those with intact vagi were ventilated by a servo-respirator which produced changes in lung volume in parallel with alterations in integrated activity of the phrenic nerve. Animals with bilateral vagotomy were ventilated with a standard respirator. 4. Aspiration of the entire cerebellar cortex did not produce alterations in levels of neural activities; the respiratory frequency was increased modestly. Following ablation of the ventrolateral portion of corpus medullare and cerebellar peduncles, expiratory activities of spinal nerves were completely eliminated whereas inspiratory activities were not greatly altered. Results were similar in animals having either intact or sectioned vagi. 5. Electrical stimulation or chemical stimulation by glutamate of regions of the ventrolateral cerebellum produced little change in respiratory neural activities except when these stimulations were within the infracerebellar nucleus. Stimulations in this nucleus caused pronounced increases in expiratory activities of spinal nerves. Neither inspiratory activities of spinal nerves nor inspiratory or expiratory activities of the recurrent laryngeal nerve were altered. Studies in animals having intact or sectioned vagi yielded similar results. 6. Bilateral lesions of neurons in the infracerebellar nucleus by injections of kainic acid in animals having intact or sectioned vagi caused an irreversible loss of expiratory activities of spinal nerves with neither inspiratory spinal activities nor inspiratory and expiratory laryngeal activities being altered. Similar findings were obtained following unilateral ablation of the infracerebellar nucleus in vagotomized cats. However, in cats with intact vagi, unilateral ablation of the infracerebellar nucleus produced only transient changes in either inspiratory or expiratory neural activities.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Differing activities of medullary respiratory neurons in eupnea and gasping.

Our purpose was to compare further eupneic ventilatory activity with that of gasping. Decerebrate, paralyzed, and ventilated cats were used; the vagi were sectioned within the thorax caudal to the laryngeal branches. Activities of the phrenic nerve and medullary respiratory neurons were recorded. Antidromic invasion was used to define bulbospinal, laryngeal, or not antidromically activated units. The ventilatory pattern was reversibly altered to gasping by exposure to 1% carbon monoxide in air. In eupnea, activities of inspiratory neurons commenced at various times during inspiration, and for most the discharge frequency gradually increased. In gasping, the peak discharge frequency of inspiratory neurons was unaltered. However, all commenced activities at the start of the phrenic burst and reached peak discharge almost immediately. The discharge frequencies of all groups of expiratory neurons fell in gasping, with many neurons ceasing activity entirely. These data are consistent with the hypothesis that brain stem mechanisms controlling eupnea and gasping differ fundamentally.

Animals

Lesions in retrotrapezoid nucleus decrease ventilatory output in anesthetized or decerebrate cats.

Kainic acid (KA) injections into the retrotrapezoid nucleus (RTN) of anesthetized deafferented cats profoundly decreased phrenic activity (PA) and CO2 sensitivity (J. Appl. Physiol. 68: 1157-1166, 1990). In this study small electrolytic lesions of the RTN produced the same results, indicating that the KA destroyed cells. We then asked whether anesthetic depression or the absence of peripheral chemoreceptors could explain the degree of respiratory depression observed. In decerebrate cats electrolytic lesions of the RTN resulted in a decrease in PA similar to that seen under anesthesia. CO2 sensitivity was decreased by RTN lesions that extended into the caudal RTN but less so than under anesthesia. KA injections resulted in an initial increase in PA followed by a continuous decrease, a pattern similar to that seen under anesthesia but with a slower time course. CO2 sensitivity was essentially absent. Peripheral chemodenervation produced a small further decrease in PA and a downward shift of the CO2 response without change in slope. Blood pressure was unaffected by RTN lesions but was decreased by more-caudal lesions without respiratory effects. The RTN appears to be necessary for the maintenance of eupneic phrenic activity and CO2 sensitivity even in decerebrate cats with intact peripheral chemoreceptors.

Anesthesia

Rostral pontile mechanisms regulate durations of expiratory phases.

Neural expiration can be divided into two phases. Phase I corresponds to the period of laryngeal adduction, whereas many spinal nerves reach peak discharge in phase II. The present studies evaluated the hypothesis that rostral pontile mechanisms contribute to determining the time of onset of spinal motoneuronal activities in phase II. In decerebrate and paralyzed cats, efferent activities were recorded from the phrenic nerve and from single fibers of the branch of the intercostal nerve innervating the triangularis sterni muscle. These activities were recorded in eupnea and apneusis; the latter was produced by cooling the rostral pons by a fork thermode. In eupnea, there was a delay between the rapid decline of phrenic discharge from peak levels and the commencement of activities of motoneurons of the triangularis sterni. This delay was significantly reduced in apneusis. Peak discharge frequencies of triangularis sterni motoneurons were the same in eupnea and apneusis. We conclude that rostral pontile mechanisms contribute significantly to defining the phases of neural expiration.

Animals

Influence of phasic volume feedback on abdominal expiratory nerve activity.

Our purpose was to examine the influence of phasic lung volume feedback on the activities of motor nerves innervating the diaphragm and transversus abdominis muscles during hypercapnia and hypoxia. We studied seventeen decerebrate cats that were paralyzed and ventilated with a servo-respirator controlled by the integrated phrenic neurogram. The effects of phasic lung volume feedback were assessed by withholding pulmonary inflation during the central inspiratory period. Withholding lung inflation for a single respiratory cycle under hyperoxic, normocapnic conditions consistently prolonged the durations of the inspiratory and expiratory periods, and caused marked increases in the peak electrical activities of both phrenic and abdominal nerves. Hyperoxic hypercapnia (PaCO2 50-80 mmHg) and isocapnic hypoxia (PaO2 60-35 mmHg) increased peak phrenic and abdominal neural activities, and withholding pulmonary inflation under these conditions caused even greater augmentations of inspiratory and expiratory motor output. The augmentation of expiratory activity by withholding lung inflation was proportionately greater than the concomitant prolongation of the central expiratory period. All responses to non-inflation maneuvers were abolished following bilateral cervical vagotomy. The results indicate that vagally mediated volume feedback during inspiration can attenuate the output of abdominal motoneurons in the subsequent expiratory period. Moreover, hypoxia, which attenuates abdominal motor activity in vagotomized animals, enhances this activity when the vagi are intact.

Animals

Discharge of vagal pulmonary receptors differentially alters neural activities during various stages of expiration in the cat.

1. The purpose was to evaluate the hypothesis that neural expiration is composed of two phases: I, a post inspiratory period; and II, the period at which expiratory activities of spinal nerves reach peak values. We hypothesized that the discharge of pulmonary stretch receptors might differentially alter neural activities during these two phases. 2. Activities of the phrenic nerve, intercostal nerve and nerves innervating the thyroarytenoid muscle of the larynx and triangularis sterni muscle of the chest wall were recorded in decerebrate and paralysed cats. 3. The experimental animals were ventilated with a servo-respirator which produced changes in tracheal pressure, and lung volume, in parallel with alterations in integrated activity of the phrenic nerve. 4. In order to assess the influence of the discharge of slowly adapting pulmonary stretch receptors upon neural activities during expiration, lung volume was held at end-expiratory or end-inspiratory levels for individual respiratory cycles. 5. When pulmonary inflation was prevented, phrenic activity increased, as did activity of the thyroarytenoid nerve during early expiration. In contrast, activities of the triangularis sterni and intercostal nerves during mid- to late expiration declined. 6. Holding the lungs at end-inspiratory levels caused a reduction of thyroarytenoid activity and increases in peak triangularis sterni and intercostal activities. Neural expiration typically continued as long as the lungs were maintained at the end-inspiratory level. 7. Responses were qualitatively similar in hypocapnia, normocapnia and hypercapnia, but the magnitude of changes in neural activities was typically augmented with elevations in end-tidal fractional concentrations of CO2. 8. We conclude that the discharge of slowly adapting pulmonary stretch receptors inhibits neural activities during early expiration and augments activities during mid-to late expiration. Hence, our data support the concept that neural expiration is composed of two stages in which neural activities may be differentially controlled.

Animals

Neurogenesis, control, and functional significance of gasping.

Gasps are frequently the first and last breaths of life. Gasping, which is generated by intrinsic medullary mechanisms, differs fundamentally from other automatic ventilatory patterns. A region of the lateral tegmental field of the medulla is critical for the neurogenesis of the gasp but has no role in eupnea. Neuronal mechanisms in separate brain stem regions may be responsible for the neurogenesis of different ventilatory patterns. This hypothesis is supported by the recording of independent respiratory rhythms simultaneously from isolated brain stem segments. Data from fetal and neonatal animals also support gasping and eupnea being generated by separate mechanisms. Gasping may represent the output of a simple but rugged pattern generator that functions as a backup system until the control system for eupnea is developed. Pacemaker elements are hypothesized as underlying the onset of inspiratory activity in gasping. Similar elements, in a different brain stem region, may be responsible for the onset of the eupneic inspiration with neural circuits involving the pons, the medulla, and the spinal cord serving to shape efferent respiratory-modulated neural discharges.

Animals

Activities of pulmonary stretch receptors during ventilatory cycles without lung inflation.

When lung inflation is temporarily withheld in paralyzed, ventilated cats with intact vagi, the activities of inspiratory motor nerves are greater during the second cycle without inflation than during the first. This response is not easily attributable to increasing drive from chemoreceptors as it is abolished by vagotomy. We examined the hypothesis that the increasing inspiratory activity is the result of decreasing inhibitory feedback from pulmonary stretch receptors (PSRs). Decerebrate, paralyzed cats were ventilated by a servo-respirator in accordance with their own phrenic nerve activity. Afferent activities from individual PSRs were recorded from a few cut fibers of one vagus nerve; the vagi were otherwise intact. When lung inflation was withheld, phrenic and hypoglossal nerve activities and the durations of inspiration and expiration all increased and were significantly greater during the second cycle without inflation than during the first. The frequency of PSR discharge was also greater during the second cycle and thus did not account for the responses recorded from the motor nerves. We conclude that the latter responses probably reflect neural processes within the brain stem, involving a persistent inhibitory influence from lung inflation, which outlasts the inflation itself.

Animals

Functions of the retrofacial nucleus in chemosensitivity and ventilatory neurogenesis.

The hypothesis was evaluated that neurons within the retrofacial nucleus of medulla integrate afferent stimuli from the central chemoreceptors. In decerebrate, vagotomized, paralyzed and ventilated cats, activity of the phrenic nerve was monitored. Peak integrated phrenic activity increased in hypercapnia; the frequency of phrenic bursts typically declined slightly. The retrofacial nucleus was ablated by radio-frequency lesions or neurons within this nucleus were destroyed by microinjections of kainic acid. Results were similar following lesions or injections. Following unilateral ablations, peak phrenic activity was greatly reduced at normocapnia and hypercapnia; the frequency of phrenic bursts typically rose. Both frequency and peak phrenic activity fell further after the contralateral destruction with a cessation of all phasic phrenic discharge being observed in most animals. Injections of kainic acid in regions rostral, caudal or medial to the retrofacial nucleus produced no consistent changes in phrenic activity. We conclude that neuronal activities in the region of the retrofacial nucleus are important both in the integration of stimuli from the central chemoreceptors and in defining the discharge patterns of respiratory neurons.

Animals

Differing control of neural activities during various portions of expiration in the cat.

1. Activities of the phrenic nerve, intercostal nerve and nerves innervating the thyroarytenoid (TA) muscle of the larynx and triangularis sterni (TS) muscle of the chest wall were recorded in decerebrate, vagotomized, paralysed and ventilated cats. 2. Neural inspiration was defined by the phase of phrenic activity. Neural expiration was divided into two phases with phase I corresponding to the duration of TA activity and phase II to TS activity: intercostal nerves discharged across both phases. 3. Phrenic activity was terminated prematurely by electrical stimulation of the superior laryngeal nerve or of the dorsolateral region of the rostral pons. Following stimulation, neural activities during phase I of expiration rose and those during phase II fell in most animals. 4. Stimulation of the superior laryngeal nerve during phase I caused augmentations of both TA and TS activity. At the termination of stimulation, a phase of TA discharge was recorded followed by a phase of TS activity. The durations of these post-stimulation phases of TA and TS activities approximated those of cycles without stimulation. 5. Stimulation of the superior laryngeal nerve during phase II caused a resetting of neural expiration. Following stimulation, phases of TA and TS activity were recorded which had durations approximating those of cycles without stimulation. 6. The current required to induce a premature onset of phrenic activity by stimulation of the dorsolateral region of the rostral pons fell dramatically with the change from phase I to phase II of expiration. 7. We conclude that the control of neural activities differs markedly between phase I and phase II of expiration. The data support the hypothesis that post-inspiratory medullary respiratory neurones play a fundamental role in the definition of the ventilatory cycle.

Animals

Expiratory neural activities in gasping.

The purpose was to characterize expiratory-related neural activities in eupnea and gasping. In decerebrate and vagotomized cats, activities were recorded from the phrenic nerve, spinal intercostal and abdominal nerves, and recurrent laryngeal nerve and its branches. Neural inspiration was defined by phrenic discharge. The spinal and laryngeal nerves discharged in inspiration, expiration, or during both phases. Gasping was induced by freezing the brain stem at the pontomedullary junction, exposure to asphyxia or anoxia, or ligation of the basilar artery and its branches. In gasping, peak phrenic activity typically increased as did inspiratory-related activities of laryngeal and spinal nerves. Expiratory activities were greatly reduced in gasping, with some activities being completely eliminated. Reductions of expiratory activity were more prominent for spinal than laryngeal nerves. Similar results were obtained in cats having intact vagi that were ventilated with a servo-respirator so that lung inflation paralleled phrenic activity. The concept that gasping differs fundamentally form other ventilatory patterns is discussed.

Animals

Respiratory activities of intralaryngeal branches of the recurrent laryngeal nerve.

To distinguish experimentally between motor nerve activity destined for vocal cord abductor muscles and that bound for muscles that adduct the cords, we recorded efferent activities of intralaryngeal branches of the recurrent laryngeal nerve (RLN) in decerebrate, vagotomized, paralyzed, ventilated cats. Activities of the whole RLN and phrenic nerve were also recorded. Nerve activities were assessed at several steady-state end-tidal O2 and CO2 concentrations. The nerve to the thyroarytenoid (TA) muscle, a vocal cord adductor, was only slightly active under base-line (normocapnic, hyperoxic) conditions but in most cats developed strong activity during expiration in hypocapnia or hypoxia. In severe hypocapnia, phasic expiratory TA activity persisted even during phrenic apnea, indicating continuing activity of the respiratory rhythm generator. The nerve to the posterior cricoarytenoid (PCA) muscle, the vocal cord abductor, was always active in inspiration but often showed expiratory activity as well. This expiratory activity was usually enhanced by hypercapnia and often inhibited by hypoxia. The results are consistent with previous electromyographic findings and emphasize the importance of distinguishing abductor from adductor activity in studies of laryngeal control.

Animals

Influence of lung volume on activities of branches of the recurrent laryngeal nerve.

To investigate the influence of inspiratory lung inflation on the respiratory activities of laryngeal motor nerves, vagally intact decerebrate paralyzed cats were ventilated by a servorespirator in accordance with their own phrenic nerve activity. Records were made of the activities of the phrenic nerve, the superior laryngeal nerve (SLN), the recurrent laryngeal nerve (RLN), and the intralaryngeal branches of the RLN serving the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles. Neural activities were assessed in the steady state at different end-tidal O2 and CO2 concentrations. Transient responses to withholding inspiratory lung inflation and to preventing expiratory lung emptying were also studied. Hypercapnia and hypoxia increased the inspiratory activities of the phrenic nerve, SLN, RLN, and its PCA branch. TA inspiratory activity was not changed. Expiratory activities of RLN, PCA, and TA were all increased in hypoxia. When lung inflation was withheld, neural inspiratory duration and the inspiratory activities of all nerves increased. The subsequent period of neural expiration was marked by an exaggerated burst of activity by the TA branch of the RLN. TA expiratory activity was also sharply increased after inspiratory efforts that were reflexly delayed by the prevention of lung emptying. TA activity in expiration was enhanced after vagotomy and was usually more prominent than when lung inflation was withheld before vagal section. The results demonstrate the importance and complexity of the influence of vagal afferents on laryngeal motor activity.

Afferent Pathways

Characterization of expiratory intercostal activity to triangularis sterni in cats.

Our purpose was to characterize activity of the intercostal nerve branch innervating the triangularis sterni muscle and the motoneuronal activities comprising this nerve discharge. In decerebrate, vagotomized, paralyzed, and ventilated cats, phasic triangularis sterni neural activity was evident in normocapnia. In most cats, activity did not commence until midexpiration. Activity then rose progressively to terminate at end expiration. Peak neural activities increased in parallel with phrenic activity in hypercapnia and fell in hypocapnia. The progressive increase in triangularis sterni neural activity within each respiratory cycle resulted from recruitment of motoneuronal activities throughout expiration. Once recruited, many motoneurons had a decrementing or constant discharge frequency. In hypercapnia, motoneuronal discharge frequencies increased, and additional activities were recruited. The number of active motoneurons and their discharge frequencies fell in hypocapnia. A similar pattern of motoneuronal activities and responses to stimuli was observed in cats with intact vagi. Factors are considered that may underlie the recruitment pattern of triangularis sterni motoneuronal activities and the inhibition of these in early expiration.

Animals

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.

Anesthesia

Respiratory-modulated activities of motor units of the facial nerve.

The purpose of this work was to characterize the influence of activity of vagal pulmonary receptors upon the discharge pattern of motor units of the facial nerve. Decerebrate and paralyzed cats were ventilated with a servo-respirator which produced pulmonary inflations in parallel with activity of the phrenic nerve. At normocapnia, facial units discharged phasically during neural inspiration, expiration or across both phases or discharged tonically throughout the respiratory cycle. When pulmonary inflation was withheld, the tonic discharge of some units became phasic; others changed the pattern of phasic discharge. In hypercapnia, the number of tonic fiber activities increased and, again, some phasic discharge patterns were altered. Withholding inflation caused similar alterations as in normocapnia. Activities of facial fibers in vagotomized animals differed in that no tonic activities were recorded, and no change in phasic discharge patterns was induced by hypercapnia. We conclude that afferents from pulmonary stretch receptors influence ventilatory activity throughout the entire respiratory cycle. The concept is discussed that the tonic, as well as phasic discharge of these receptors, is important for the regulation of activity of motoneurons to upper airway muscles.

Animals