Breathing disorders during sleep.
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Arousal↗
Biomedical subjects
N S Cherniack
Publications and source records attributed to N S Cherniack.
Stimulation of respiratory changes in alae nasi length by chemoreceptor activation.
Respiratory-related changes in length of the nasal dilator muscle, the alae nasi muscle, were measured using sonomicrometry in ten anesthetized (pentobarbital), tracheostomized, spontaneously breathing dogs. Piezoelectric crystals were inserted 7-25 mm apart along the direction of the alae nasi muscle fibers, and the effects of progressive hyperoxic hypercapnia and a peripheral and central chemoreceptor stimulant, nicotine (10-500 micrograms intravenously), were ascertained. The alae nasi shortened during inspiration in all animals, started to lengthen again towards the end of inspiration, returned to resting length during the first portion of expiration (Te-1), and remained at resting length for the remainder of expiration (Te-2). The amount of alae nasi inspiratory shortening was increased by occluding the airway for a single breath. Progressive hypercapnia caused progressive increases in the amount and velocity of nasal muscle inspiratory shortening during both unoccluded and occluded breaths; similar stimulatory effects on inspiratory shortening were seen following nicotine administration. Furthermore, both chemoreceptor stimulants caused a delay in the return of the muscle to its resting length during expiration, resulting in a significant increase in Te-1 relative to Te (Te-1/Te), and a greater amount of nasal muscle shortening to be present during Te-1. In some animals these agents also caused tonic shortening of the alae nasi, so that the muscle never returned to its resting length. These results suggest that inspiratory shortening of the alae nasi is inhibited by vagal inputs, but that chemoreceptor activation increases the amount of muscle shortening during both inspiration and early expiration.
Animals↗
Medullary effects of nicotine and GABA on tracheal smooth muscle tone.
Airway tone can be modulated centrally by the brain as well as by peripheral receptors. In part these changes in airway caliber seem to be secondary to changes in respiratory activity. Since structures near the ventrolateral medullary surface (VMS) can produce profound effects on respiration, it seems reasonable to believe that they might also be capable of modifying tracheal tone. In this study we examined the effects of two agents with respect to their action on tracheal tone: nicotine, a respiratory stimulant when applied to the VMS, and gamma aminobutyric acid (GABA), a respiratory depressant when similarly administered. In chloralose anesthetized, paralyzed, artificially ventilated cats, tracheal tone was assessed by measuring pressure changes in a rostral bypassed segment of the trachea, while phrenic nerve activity was examined simultaneously. Nicotine administered on the intermediate area of the VMS both before and after carotid sinus denervation increased phrenic activity and induced constriction of the rostral tracheal segment. The response to nicotine could be blocked by application of a nicotine antagonist, hexamethonium, or prior local administration of lidocaine to the VMS. Activation of GABAergic receptors by application of GABA on the intermediate area of the VMS markedly reduced respiratory activity and nearly abolished the increased tracheal tone produced by inhalation of 7% CO2 in O2. The effects of GABA were eliminated by the prior administration to the VMS of bicuculline, a GABA receptor antagonist. These results indicate that structures located on the ventral surface of the medulla which affect breathing may also play a significant role in the regulation of airway smooth muscle tone.
Administration, Topical↗
Comparison of the effects of hypercapnia on phrenic and hypoglossal activity in anesthetized decerebrate and decorticate animals.
To examine the effects of suprapontine structures on the activity of hypoglossal and phrenic nerves, 13 chloralose anesthetized, paralyzed (gallamine triethiodide) and artificially ventilated cats were studied. In all animals vagi and carotid sinus nerves were cut bilaterally. All animals were first hyperventilated to apnea and then made progressively hypercapnic by rebreathing under hyperoxic conditions. Following midcollicular decerebration, the peak phasic activity of the hypoglossal nerve was significantly depressed and the PCO2 at which apnea occurred (apneic point) increased. However, following high decerebration or decortication the activity of the hypoglossal nerve was increased at higher CO2 levels and there was no change in apneic point. By contrast, peak phrenic nerve activity was not altered by any of the above surgical procedures. Neither systemic blood pressure nor respiratory frequency were significantly altered by these procedures. The results indicate that suprapontine structures can appreciably modify hypoglossal activity.
Anesthesia, General↗
Effect of hypoxia on ventilatory and arousal responses to CO2 during NREM sleep with and without flurazepam in young adults.
We examined the ventilatory response to CO2 at two levels of oxygenation during wakefulness and sleep in healthy young adults before and after the ingestion of a single dose of 30 mg flurazepam. Progressive hypercapnia was produced at two levels of arterial O2 saturation (greater than 99 and 87%) by having subjects re-breathe from a tight-fitting face mask and a reservoir bag containing gas mixtures with two different O2 concentrations. Ventilation was measured with an inductive plethysmograph. O2 saturation was measured with an ear oximeter. Sleep was monitored using standard techniques by recording the electroencephalogram, eye movements, and chin electromyogram. During wakefulness, hypoxia increased the slope of the ventilatory response to CO2 and shifted the response slightly to the left. NREM sleep lowered the slope of the CO2 response under both hyperoxic and hypoxic conditions. The slope of the hyperoxic CO2 response curve was not affected by flurazepam during wakefulness or sleep. After administration of flurazepam to the subjects, the shift of the CO2 response curve to the left produced by hypoxia (additive effect) during NREM sleep was slightly less as compared to control, but hypoxia still increased the slope of the CO2 ventilatory response. During hypoxic hypercapnia, the PCO2 at arousal from sleep was significantly lower than during hyperoxic hypercapnia, but the level of ventilation at arousal during hypercapnia was similar in the control condition and after flurazepam. We conclude that (a) both natural and flurazepam-induced sleep depress ventilatory responses to hyperoxic and hypoxic hypercapnia and alter, in a complex fashion, the effects of hypoxia and hypercapnia on ventilation; and (b) hypoxia and hypercapnia interact as arousal stimuli in both natural and flurazepam-induced sleep.
Adult↗
Effect of focal cooling of central chemosensitive areas on cerebral ischemic response.
The ventrolateral medullary surface (VMS) has been shown to have chemosensitive areas that can alter blood pressure and respiration. It has also been shown that lesions near the VMS can affect the intensity of the cerebral ischemic response (CIR). To determine which regions of the central chemosensitive areas of the ventral medullary surface contribute to the pressor response caused by cerebral ischemia, we used focal cooling of the caudal Loescheke's (CL), intermediate Schlaefke's (IS), and rostral Mitchell's (RM) areas of VMS during ischemia of the brain. Experiments were performed on 17 pentobarbital sodium-anesthetized, paralyzed, and artificially ventilated cats after denervation of the vagi and sinoaortic nerves. Bilateral occlusion of the external carotid and vertebral arteries resulted in a significant increase of arterial pressure (from 129 +/- 4 to 174 +/- 8 mmHg, P less than 0.01) and an increase in splanchnic sympathetic activity. However, heart rate and cervical sympathetic activities were not appreciably affected by cerebral ischemia. Bilateral cooling of the IS area to as low as 10 degrees C led to a decrease or disappearance of phrenic activity but failed to affect the magnitude of the pressor response. Also cooling of the CL and RM areas and application of Gelfoam pledgets soaked in lidocaine (4%) to these areas did not affect the CIR. However, covering the whole VMS with 0.2 ml of 4% lidocaine or cold cerebrospinal fluid (10 degrees C) abolished the ischemic reflex.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Topical↗
Electrical and mechanical activity of respiratory muscles during hypercapnia.
In nine anesthetized supine spontaneously breathing dogs, we compared moving average electromyograms (EMGs) of the costal diaphragm and the third parasternal intercostal muscles with their respective respiratory changes in length (measured by sonomicrometry). During resting O2 breathing the pattern of diaphragm and intercostal muscle inspiratory shortening paralleled the gradually incrementing pattern of their moving average EMGs. Progressive hypercapnia caused progressive increases in the amount and velocity of respiratory muscle inspiratory shortening. For both muscles there were linear relationships during the course of CO2 rebreathing between their peak moving average EMGs and total inspiratory shortening and between tidal volume and total inspiratory shortening. During single-breath airway occlusions, the electrical activity of both the diaphragm and intercostal muscles increased, but there were decreases in their tidal shortening. The extent of muscle shortening during occluded breaths was increased by hypercapnia, so that both muscles shortened more during occluded breaths under hypercapnic conditions (PCO2 up to 90 Torr) than during unoccluded breaths under normocapnic conditions. These results suggest that for the costal diaphragm and parasternal intercostal muscles there is a close relationship between their electrical and mechanical behavior during CO2 rebreathing, this relationship is substantially altered by occluding the airway for a single breath, and thoracic respiratory muscles do not contract quasi-isometrically during occluded breaths.
Animals↗
Influence of ventrolateral surface of medulla on reflex tracheal constriction.
To assess the role of structures located superficially near the ventrolateral surface of the medulla on the reflex constriction of tracheal smooth muscle that occurs when airway and pulmonary receptors are stimulated mechanically or chemically, experiments were conducted in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats. Pressure changes within a bypassed segment of the trachea were used as an index of alterations smooth muscle tone. The effects of focal cooling of the intermediate areas or topically applied lidocaine on the ventral surface of the medulla on the response of the trachea to mechanical and chemical stimulation of airway receptors were examined. Atropine abolished tracheal constriction induced by mechanical stimulation of the carina or aerosolized histamine, showing that the responses were mediated over vagal pathways. Moderate cooling of the intermediate area (20 degrees C) or local application of lidocaine significantly decreased the tracheal constrictive response to mechanical activation of airway receptors. Furthermore, when the trachea was constricted by histamine, cooling of the intermediate area significantly diminished the increased tracheal tone, whereas rewarming restored tracheal tone to the previous level. These findings suggest that under the conditions of the experiments the ventral surface of the medulla plays an important role in constriction of the trachea by inputs from intrapulmonary receptors and in the modulation of parasympathetic outflow to airway smooth muscle.
Administration, Topical↗
Influence of the ventral surface of the medulla on tracheal responses to CO2.
These studies investigated the role of the intermediate area of the ventral surface of the medulla (VMS) in the tracheal constriction produced by hypercapnia. Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. Airway responses were assessed from pressure changes in a bypassed segment of the rostral cervical trachea. Hyperoxic hypercapnia increased tracheal pressure and phrenic nerve activity. Intravenous atropine pretreatment or vagotomy abolished the changes in tracheal pressure without affecting phrenic nerve discharge. Rapid cooling of the intermediate area reversed the tracheal constriction produced by hypercapnia. Graded cooling produced a progressive reduction in the changes in maximal tracheal pressure and phrenic nerve discharge responses caused by hypercapnia. Cooling the intermediate area to 20 degrees C significantly elevated the CO2 thresholds of both responses. These findings demonstrate that structures near the intermediate area of the VMS play a role in the neural cholinergic responses of the tracheal segment to CO2. It is possible that neurons or fibers in intermediate area influence the motor nuclei innervating the trachea. Alternatively, airway tone may be linked to respiratory motor activity so that medullary interventions that influence respiratory motor activity also alter bronchomotor tone.
Animals↗
Analysis of postinspiratory activity of phrenic motoneurons with chemical and vagal reflexes.
We examined the effects of chemical and reflex drives on the postinspiratory inspiratory activity (PIIA) of phrenic motoneurons using a single-fiber technique. Action potentials from "single" fibers were recorded from the C5 phrenic root together with contralateral mass phrenic activity (also from C5) in anesthetized, paralyzed, and artificially ventilated cats with intact vagus and carotid sinus nerves. Nerve fibers were classified as "early" or "late" based on their onset of discharge in relation to mass phrenic activity during hyperoxic ventilation. Only the early fibers displayed PIIA but not the late fibers, even when their activity began earlier in inspiration with increased chemical drives. Isocapnic hypoxia increased, whereas hyperoxic hypercapnia shortened the duration of PIIA. Pulmonary stretch and "irritant" receptors inhibited PIIA. Hypercapnia and stimulation of peripheral chemoreceptors by lobeline excited both early and late units to the same extent, but hypoxic ventilation had a less marked excitatory effect on late fiber activity. Irritant receptor activation increased the activity of early more than late fibers. Hyperoxic hyperventilation eliminated late phrenic fiber activity, whereas early fibers became tonically active. Bilateral vagotomy abolished this sustained discharge in eight of nine early units, suggesting the importance of vagal afferents in producing tonic firing during hyperventilation. These results suggest that early and late phrenic fibers have different responses to chemical stimuli and to vagally mediated reflexes; late units do not discharge in postinspiratory period, whereas early fibers do; the PIIA is not affected in the same way by various chemical and vagal inputs; and early units that exhibit PIIA display tonic activity with hyperoxic hypocapnia.
Action Potentials↗
Responses of hypoglossal and phrenic nerves to decreased respiratory drive in cats.
Agents which depress respiration, such as alcohol, seem to increase the occurrence of obstructive apneas during sleep. It has been proposed that upper airway obstruction can result from an imbalance in the activity (or forces) produced by the upper airway muscles versus the chest wall muscles so that upper airway passages might be blocked when a disproportionate decrease in upper airway muscle activity occurs. This study examines the hypothesis that depression of respiration affects the activity of the hypoglossal nerve (the motor nerve to the tongue) more than the activity of the phrenic nerve (the motor nerve to the diaphragm). In addition, we examined the role of the putative central chemoreceptor area on the ventrolateral medullary surface (VMS) in maintaining phrenic and hypoglossal discharge. In chloralose-anesthetized, artificially ventilated, paralyzed cats, three methods of reducing respiratory drive were studied: hyperoxic hypocapnia (produced by mechanical hyperventilation), the application to the intermediate area of the ventral medullary surface of the respiratory depressant GABA and its agonist muscimol, and cooling the same area of the VMS (using a water-cooled thermode). All these interventions decreased hypoglossal nerve activity more than phrenic nerve activity (range of p values: p less than 0.001 to p less than 0.01). Moreover, the reduction in hypoglossal activity was greater with GABA and muscimol than with the other two maneuvers; this was statistically significant for both GABA versus VMS cooling (p less than 0.02) and muscimol versus VMS cooling (p less than 0.01). These results show that respiratory depression can differentially affect hypoglossal and phrenic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Physiologic basis of therapy for sleep apnea.
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Animals↗
Costal and crural diaphragm and intercostal muscle activity during augmented breaths in cats.
The pattern of electrical activity of the costal and crural diaphragm and the external intercostal muscles was ascertained in ten anesthetized spontaneously breathing cats during eupnea and during augmented breaths. All muscles studied manifested a biphasic activity pattern during augmented breaths. The increase in activity during the latter portion (phase II) of the augmented breaths was greater for the crural than the costal diaphragm (P less than 0.05), and greater for cranially located intercostal muscles than for the costal diaphragm (P less than 0.02) and more caudally located intercostal muscles (P less than 0.02). These results suggest that during augmented breaths, activity of different thoracic muscles is modulated in a non-uniform manner.
Animals↗
The effects of hypercapnia and cooling the ventral medullary surface on capsaicin induced respiratory reflexes.
The effect of right atrial (RA) injection of 3 micrograms/kg capsaicin on phrenic, hypoglossal and recurrent laryngeal activities was studied in chloralose anesthetized, paralyzed and artificially ventilated cats. Within 2 sec following capsaicin injection, the phrenic and hypoglossal activities completely disappeared (apnea), while the recurrent laryngeal activity markedly increased. Similar responses were also obtained with RA injection of phenyldiguinide (PDG), suggesting that the respiratory responses of both drugs are essentially similar. Sino-aortic denervation did not affect the capsaicin induced respiratory responses. Bilateral vagotomy abolished the responses, suggesting that vagal sensory receptors are responsible for the reflex effects. Hyperoxic hypercapnia (3 and 7% CO2 in O2) reduced the apneic duration of phrenic and hypoglossal nerves. The magnitude of the recurrent laryngeal excitation was decreased during CO2 breathing. Graded focal cooling of the intermediate area (Is area) of the ventral medullary surface (to inhibit central chemoreceptor activity) significantly prolonged capsaicin induced apneic duration of hypoglossal nerves more than the phrenic. The recurrent laryngeal responses, however, were unaffected by cooling of the ventral medullary surface. The results show that capsaicin and PDG, presumably by stimulating C fibers, affect cranial nerves as well as the phrenic. The reflex responses to C fiber stimulation seem to be altered by intervention which stimulate (hypercapnia) or depress (Is cooling) 'central chemoreceptors.'
Animals↗
Effects of age and respiratory efforts on the perception of resistive ventilatory loads.
The present study examined the effects of age on the ability to quantitate changes in inspiratory resistive loads using signals related to the size of the load, per se. Magnitude scaling of inspiratory resistive loads was performed in different trials during breathing at small, large, and varied size tidal volumes. Subjects were specifically instructed to scale the magnitude of the airflow resistance. In both young and older adults, the perceived magnitude of a given resistance was the same in the small-, large-, and varied-sized breath trials despite substantial differences in inspiratory duration and peak inspiratory airway pressure. The change in sensation for a given change in resistance, however, was less in the older than in the younger adults. These results indicate that airflow resistance can be scaled independently of the effort used in breathing. The perception of airflow resistance is blunted in elderly adults probably as a result of an impairment in the central nervous system processing of separate signals of pressure and flow.
Adolescent↗
Influence of central chemoreceptor afferent inputs on respiratory muscle activity.
Respiratory activity can be substantially affected by perturbations confined to the superficial areas of the ventrolateral surface of the medulla, the putative site of central chemoreceptors. In this study we compared the effect of thermal and pharmacological interventions that are known to alter respiration on the electrical activity of the rib cage muscles, diaphragm, and abdominal muscles. With cooling of the intermediate areas to 20 degrees C, tidal volume decreased 50%. The electrical activity of the diaphragm decreased less than the other muscles (diaphragm less than inspiratory intercostal less than expiratory intercostal). Abdominal muscle activity was depressed as much as expiratory intercostal activity but reappeared with further cooling to 10 degrees C if cooling was prolonged and the vagi were intact. gamma-Aminobutyric acid (GABA) and its agonist muscimol, like cooling, reduced expiratory and inspiratory intercostal activity more than diaphragm activity. Nicotine, a respiratory stimulant, applied to the intermediate areas increased inspiratory intercostal activity more than the diaphragm. The results suggest that under the conditions of the experiments the rib cage musculature, and probably the abdominal muscles as well, are more responsive than the diaphragm to depression or excitation of chemosensitive elements in the superficial regions of the medulla.
Animals↗
Differential costal and crural diaphragm compensation for posture changes.
The electromyographic (EMG) activities of the costal and crural diaphragm were recorded from bipolar fine-wire electrodes placed in the costal fibers adjacent to the central tendon and in the anterior portions of the crural fibers in 12 anesthetized cats. The EMG activities of costal and crural recordings were compared during posture changes from supine to head up and during progressive hyperoxic hypercapnia in both positions. The activity of both portions of the diaphragm was greater in the head up compared with supine posture at all levels of CO2; and increases in crural activity were greater than those in costal activity both as a result of changes in posture and with increasing CO2 stimuli. These results are consistent with the concept that diaphragm activation is modulated in response to changes in resting muscle length, and further, that neural control mechanisms allow separate regulation of costal and crural diaphragm activation.
Adaptation, Physiological↗
Respiratory changes in nasal muscle length.
Respiratory changes in alae nasi muscle length were recorded using sonomicrometry in pentobarbital sodium-anesthetized tracheostomized dogs spontaneously breathing 100% O2. Piezoelectric crystals were inserted via small incisions into the alae nasi of 11 animals, and bipolar fine-wire electrodes were inserted contralaterally in nine of the same animals. The alae nasi shortened during inspiration in all animals. The mean amount of shortening was 1.33 +/- 0.22% of resting length (LR), and the mean velocity of shortening during the first 200 ms was 4.60 +/- 0.69% LR/S. The onset of alae nasi shortening preceded inspiratory flow by 77 +/- 18 ms (P less than 0.002), at which time both alae nasi shortening and the moving average of electromyographic (EMG) activity had reached approximately one-third of their peak values. In contrast, there was a relative delay in alae nasi relaxation relative to the decay of alae nasi EMG at the end of expiration. Single-breath airway occlusions at end expiration changed the normally rounded pattern of alae nasi shortening and moving average EMG to a late-inspiratory peaking pattern; both total shortening and EMG were increased by similar amounts. The onset of vagally mediated volume-related inhibition of alae nasi shortening occurred synchronously with the onset of inhibition of alae nasi EMG; both occurred at lung volumes substantially below tidal volume. These results indicate that the pattern of inspiratory shortening of this nasal dilating muscle is reflected closely in the pattern of EMG activity and that vagal afferents cause substantial inhibition of alae nasi inspiratory shortening.
Animals↗