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Biomedical subjects

D Bartlett

Publications and source records attributed to D Bartlett.

At least 91 records · Page 5Linked to original sources

Postnatal development of the lung following denervation.

We asked to what extent pulmonary innervation influences the postnatal development of the lung. To this end we performed cervical vagotomy and sympathectomy either on the right or on the left side in young rats and rabbits and rats after weaning. One to four weeks later we examined the lungs of the denervated side, the contralateral intact side of the same animal, and sham-operated controls. Dry lung weight, lung volume and the size of subpleural alveoli were not different among the three groups. Lung mechanical properties (static and dynamic lung compliances, lung resistance, frequency dependence of compliance), measured in rabbits, were also not different among groups of lungs, suggesting that neither central nor peripheral airways were markedly affected by the denervation. The breathing pattern, measured in the rats after weaning, was characterized by a larger tidal volume in the denervated animals than in controls, as expected after the partial pulmonary afferent denervation. The absence of major structural and functional changes in the lungs of these animals suggests that an increase in the mechanical stretch to the lung above that normally occurring during resting breathing does not influence the lung structure. We conclude that pulmonary innervation does not play an important role in the postnatal development of the lung.

Animals↗

Influence of extreme hypercapnia on respiratory motor nerve activity in cats.

Sedative drugs have been found to depress the respiratory activity of upper airway muscles more than that of the diaphragm. To determine whether CO2 at narcotic levels has a similar action, we recorded phrenic and hypoglossal nerve activities in decerebrate, vagotomized, paralyzed cats. T5 or T6 external intercostal nerve activity was also recorded in some animals. End-tidal CO2 concentration was raised progressively to over 30% or until depression of nerve activity was apparent. Respiratory frequency was reduced by severe hypercapnia in most cats. Hypoglossal nerve activity was consistently decreased more than that of the phrenic nerve. In most cases intercostal nerve activity was also more susceptible than phrenic nerve activity to hypercapnic depression. The results indicate that CO2 at narcotic levels interferes both with the central pattern generator for breathing movements and with the expression of the pattern in specific motor nerves.

Animals↗

The use of epidural bupivacaine for the relief of childbirth pain.

Epidural anaesthesia is now a widely used method for pain relief in childbirth, particularly using the drug Bupivacaine. There are nevertheless differing opinions in the research literature about the advisability of its routine use. While it is clearly very effective in relieving labour pain, there are some consistent, troublesome patterns; for example, a strong association between epidural use and other interventions, such as instrumental delivery. Further, there are no clear answers from the research to date concerning the risks and benefits of epidural anaesthesia for infant and mother. Answers could be provided by randomized clinical trials, but meanwhile a conservative approach to its use is recommended for uncomplicated labours.

Anesthesia, Epidural↗

Hypoxia inhibits abdominal expiratory nerve activity.

Our purpose was to examine the influence of steady-state changes in chemical stimuli, as well as discrete peripheral chemoreceptor stimulation, on abdominal expiratory motor activity. In decerebrate, paralyzed, vagotomized, and ventilated cats that had bilateral pneumothoraces, we recorded efferent activity from a phrenic nerve and from an abdominal nerve (cranial iliohypogastric nerve, L1). All cats showed phasic expiratory abdominal nerve discharge at normocapnia [end-tidal PCO2 38 +/- 2 Torr], but small doses (2-6 mg/kg) of pentobarbital sodium markedly depressed this activity. Hyperoxic hypercapnia consistently enhanced abdominal expiratory activity and shortened the burst duration. Isocapnic hypoxia caused inhibition of abdominal nerve discharge in 11 of 13 cats. Carotid sinus nerve denervation (3 cats) exacerbated the hypoxic depression of abdominal nerve activity and depressed phrenic motor output. Stimulation of peripheral chemoreceptors with NaCN increased abdominal nerve discharge in 7 of 10 cats, although 2 cats exhibited marked inhibition. Four cats with intact neuraxis, but anesthetized with ketamine, yielded qualitatively similar results. We conclude that when cats are subjected to steady-state chemical stimuli in isolation (no interference from proprioceptive inputs), hypercapnia potentiates, but hypoxia attenuates, abdominal expiratory nerve activity. Mechanisms to explain the selective inhibition of expiratory motor activity by hypoxia are proposed, and physiological implications are discussed.

Abdomen↗

Influence of pulmonary inflations on discharge patterns of phrenic motoneurons.

The purpose of this study was to assess the influence of pulmonary inflations on activities of single phrenic motoneurons. Studies were performed in decerebrate and paralyzed cats; activities of phrenic nerve and single phrenic motoneurons were recorded. Animals were ventilated with a servo-respirator which produced alterations in tracheal pressure in parallel with changes in integrated activity of the phrenic nerve. At end-tidal fractional concentrations of CO2 of 0.05, phrenic motoneurons were distributed into "early" and "late" populations, depending on time of onset of activity. During the late stages of neural inspiration, differences in levels of integrated activity of the phrenic nerve became evident between cycles with and without lung inflations. At a time approximating 90% of the inspiratory duration during inflations, integrated phrenic activity was higher for cycles with inflation. Concomitantly, with lung inflations, the discharge frequencies of early phrenic motoneurons were lower, and late motoneurons began to discharge sooner than when inflations were withheld. Similar results were obtained in hypercapnia. We conclude that reflexes activated by pulmonary inflations may produce augmentation, as well as inhibition of phrenic motoneuronal activities. Factors responsible for eliciting these reflex augmentations and inhibitions are discussed.

Animals↗

Respiratory activity of genioglossus. Interaction between alcohol and the menstrual cycle.

Alcohol consistently decreases genioglossal electromyographic (EMG) activity in awake men, but in women this response is more variable, possibly because of the menstrual cycle. To assess the interaction between alcohol and the menstrual cycle on genioglossal EMG activity, we measured ventilation and genioglossal EMG activity in 9 normal women before and after they drank 1 ml/kg alcohol. The effect of alcohol on ventilation and genioglossal EMG activity was studied twice in each subject: once during the follicular phase and again during the luteal phase of the menstrual cycle. Measurements were made while the subjects breathed room air and rebreathed a hypercapnic gas mixture. The ventilatory response to CO2 was significantly greater during the luteal phase of the menstrual cycle. Alcohol had no effect on resting ventilation or the ventilatory response to CO2 during either phase of the menstrual cycle. However, alcohol significantly decreased peak integrated genioglossal EMG activity during the follicular (low progesterone) phase but not during the luteal (high progesterone) phase of the cycle. The relative alcohol resistance of genioglossal EMG activity during the luteal phase may explain in part the low incidence of sleep-disordered breathing in premenopausal women and the benefit that some male patients with obstructive sleep apnea have derived from treatment with progesterone.

Adult↗

Respiratory mechanics and control of the ventilatory cycle in the garter snake.

We measured respiratory airflow and intrapulmonary pressure in spontaneously breathing garter snakes (Thamnophis sirtalis) before and after bilateral vagotomy. Each breathing cycle consisted of expiration, inspiration, and a breath-holding period with the glottis closed, as previously reported. Respiratory system compliance was very high compared with that of mammals (0.042 ml/cm H2O per g), but was considerably reduced when the animal was coiled. Resistance to airflow averaged 6.35 cm H2O per ml/sec. Lung volume during the breath-hold was usually above the relaxed volume of the system. Analysis of dynamic pressure-volume and flow-volume loops showed that both expiration and inspiration were active, and that little use was made of passive recoil pressure in expiration. Evidence that vagally mediated, volume-related feedback influenced the breathing pattern was found in some snakes, but this influence was weaker than in most mammals and other reptiles. The results suggest that breathing in snakes is mainly a centrally programmed process, not markedly dependent on respiratory system mechanics or neuromechanical feedback. This arrangement is advantageous in view of the high, posturally variable compliance and the frequent regional distortions of the respiratory system that result from the unique structure of these animals.

Airway Resistance↗

Influence of morphine on respiratory activities of phrenic and hypoglossal nerves in cats.

Anesthetic and sedative drugs have been found to diminish the respiratory motor activity of the hypoglossal nerve more than that of the phrenic nerve. This differential depression of motor activity to the upper airway may contribute to the exacerbation of obstructive sleep apnea by sedative drugs. To determine whether morphine has a similar selective action, we recorded phrenic and hypoglossal nerve activities before and after morphine administration in decerebrate, vagotomized cats, paralyzed with gallamine. Morphine diminished the activities of both nerves in most animals, but the responses were highly variable, and no consistent pattern of differential depression was apparent. The variability of the results may reflect the complex nature of opiate actions on the control of breathing.

Animals↗

Differential depression of hypoglossal nerve activity by alcohol. Protection by pretreatment with medroxyprogesterone acetate.

Upper airway obstruction during sleep occurs more commonly in men than in women and has been treated with progestational agents with some success. Alcohol ingestion exacerbates sleep apnea, and recent studies have established that alcohol depresses the respiratory motor activity to upper airway muscles more than that to the diaphragm, a response pattern that favors upper airway obstruction during inspiration. To investigate the possibility that progesterone provides some protection from this action of alcohol, we studied the responses of phrenic and hypoglossal nerve activities to alcohol infusion in decerebrate cats pretreated with medroxyprogesterone acetate (MPA) or with control injections. The results indicate that pretreatment with MPA reduces the alcohol-induced mismatching of hypoglossal and phrenic activities. This action of MPA may contribute to its effectiveness in the treatment of some patients with inspiratory obstruction during sleep.

Action Potentials↗

Enhancement of respiratory response to carbon dioxide produced by lesioning caudal regions of the nucleus of the tractus solitarius.

Bilateral lesions of the caudal region of the nucleus of the tractus solitarius produced a significant enhancement of the ventilatory response to carbon dioxide in awake rats. The result indicates release of an inhibitory influence normally operating at hindbrain level. Respiration in air or oxygen was not affected while hypoxic responses were depressed insignificantly.

Animals↗

Comparison of phrenic motoneuron activity in eupnea and apneusis.

Our purpose was to characterize activities of phrenic motoneurons during apneusis. In decerebrate, cerebellectomized, vagotomized, paralyzed and ventilated cats, we recorded activities of phrenic nerve and single phrenic fibers during eupnea and apneusis. Reversible apneusis was obtained by cooling the rostral pons with a fork thermode. Phrenic motoneurons were defined as 'early' or 'late' during eupnea. Early units commenced activity before or during the first 20% of neural inspiration. The onset of discharge of late units extended throughout the rest of inspiration. In apneusis, some late units ceased activity entirely; others commenced activity at the end of the rising phase of phrenic activity or during the apneustic plateau. Early units commenced activities at the same time as in eupnea and generally maintained the same discharge frequency. Hence, the ramp phase of phrenic discharge in apneusis is generated largely by activities of early motoneurons. Our results imply that the level of bulbospinal activity impinging upon the phrenic nucleus is reduced in apneusis. The integration of efferent activity within the phrenic nucleus is discussed.

Action Potentials↗

Changes in upper airway muscle activity related to head position in awake cats.

The influence of head position on the respiratory activity of the diaphragm (DIA), posterior cricoarytenoid (PCA) and genioglossus (GG) muscles was studied in conscious cats with chronically implanted electromyographic electrodes. Tracheal pressure was also recorded through a small implanted catheter. Spontaneous or passive downward movements of the head resulted in sustained increases in the respiratory excursions of tracheal pressure and in PCA and GG activities. Conversely, these variables all decreased when the head was raised. Activity of the DIA was little affected. In animals with chronic tracheostomies, which greatly diminished tracheal pressure excursions and their changes with head movements, the postural responses of PCA and GG activities persisted, but were attenuated. The responses also persisted after bilateral superior laryngeal nerve section. These findings demonstrate responses that act to maintain the patency of the upper respiratory tract, probably by reflex mechanisms. Receptors in the upper airway contribute to the responses, but other afferents - possibly from vestibular or joint receptors - are also involved.

Animals↗

A noninvasive intraoral electromyographic electrode for genioglossus muscle.

We have developed an intraoral bipolar surface electrode for the genioglossus muscle. The electrode, made from an athletic mouthguard and dental impression material, was fitted to the lower teeth. Electrode wires, bared at the tip, were positioned on the bottom of the mouthpiece to lie in contact with the superior surface of the genioglossus just behind the teeth. The electromyographic activity of the genioglossus, simultaneously obtained from the surface electrode and conventional intramuscular electrodes, was compared during quiet breathing, CO2 rebreathing, and a variety of tongue movements. The two types of electrodes recorded similar patterns of muscle activity, and spectral analyses of the signals revealed similar and highly coherent frequency spectra. We conclude that the surface electrode satisfactorily reflects the bioelectrical activity of the genioglossus. The mouthpiece electrode has the further advantage that quantitative comparisons can be made among recordings made in different experimental sessions, since the fit of the mouthpiece to the teeth assures a constant relationship of the electrode to the genioglossus muscle.

Adult↗

The effect of diazepam on genioglossal muscle activity in normal human subjects.

We examined the effect of diazepam on the respiratory electromyographic (EMG) activity of the genioglossal muscle using a double-blind, placebo-controlled, randomized protocol. Control measurements of minute ventilation, tidal volume, frequency, end-tidal CO2, and peak integrated inspiratory genioglossal EMG activity were made in 10 normal awake male subjects during quiet breathing and CO2 rebreathing. Subjects then received either 10 mg of diazepam orally or a placebo, and all respiratory measurements were repeated after 45 min. Each subject was studied on 2 separate days, receiving each treatment on a different day. The placebo had no effect on any of the measured variables. After diazepam, we observed an increase in end-tidal CO2 rebreathing, diazepam was associated with a reduction in minute ventilation, tidal volume, and frequency. When compared at equal end-tidal CO2 levels, genioglossal EMG activity and tidal volume were significantly reduced after diazepam. However, only older subjects demonstrated a reduction in EMG activity when compared at equal tidal volumes during CO2 rebreathing. We conclude that diazepam selectively decreases genioglossal EMG activity during CO2 rebreathing only in older subjects.

Adult↗

The effect of sleep deprivation on activity of the genioglossus muscle.

Sleep deprivation appears to increase the severity of obstructive sleep apnea, and inadequate activation of the genioglossus muscle may play an important role in the pathogenesis of obstructive sleep apnea. Therefore, we investigated the effect of sleep deprivation on genioglossal electromyographic (EMG) activity. Eleven men were studied during room air breathing and CO2 rebreathing before sleep deprivation (control), after 1 night of sleep deprivation, and the day after sleep recovery. We measured inspired minute ventilation, tidal volume, respiratory frequency, and peak integrated inspiratory genioglossal EMG activity. After sleep deprivation, no significant changes in inspiratory minute ventilation or tidal volume occurred during room air breathing or CO2 rebreathing, but the breathing frequency during CO2 rebreathing increased significantly after sleep deprivation. Genioglossal EMG activity was diminished during CO2 rebreathing after sleep deprivation, but this was significant only in subjects 30 yr of age and older. The fall in EMG activity was independent of changes in tidal volume. All variables returned towards control levels after sleep recovery. We conclude that sleep deprivation selectively decreases genioglossal EMG activity during CO2 rebreathing in awake older subjects. This influence of sleep deprivation may play a role in the pathogenesis or severity of obstructive sleep apnea.

Adult↗

Human vocal cord movements during voluntary hyperventilation.

Using a fiberoptic laryngoscope and video equipment, we studied the respiratory movements of the vocal cords during sustained hyperventilation in 4 normal human subjects. The expiratory narrowing of the glottic airway that occurs in quiet breathing was attenuated during hyperventilation in 7 of 8 experiments, and the pattern of vocal cord movements throughout the breathing cycle closely resembled the patterns previously found in exercise and hypercapnia. These responses were similar during normocapnic and hypocapnic hyperventilation. The similarity of laryngeal movements in voluntary and involuntary hyperpneic states suggests that common brain stem mechanisms may be entrained by both 'behavioral' and 'automatic' ventilatory control systems.

Adult↗

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.

Afferent Pathways↗

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.

Animals↗