Search PubMed⌕ Search

Biomedical subjects

E N Bruce

Publications and source records attributed to E N Bruce.

At least 55 records · Page 3Linked to original sources

Possible mechanisms of periodic breathing during sleep.

To determine the effect of respiratory control system loop gain on periodic breathing during sleep, 10 volunteers were studied during stage 1-2 non-rapid-eye-movement (NREM) sleep while breathing room air (room air control), while hypoxic (hypoxia control), and while wearing a tight-fitting mask that augmented control system gain by mechanically increasing the effect of ventilation on arterial O2 saturation (SaO2) (hypoxia increased gain). Ventilatory responses to progressive hypoxia at two steady-state end-tidal PCO2 levels and to progressive hypercapnia at two levels of oxygenation were measured during wakefulness as indexes of controller gain. Under increased gain conditions, five male subjects developed periodic breathing with recurrent cycles of hyperventilation and apnea; the remaining subjects had nonperiodic patterns of hyperventilation. Periodic breathers had greater ventilatory response slopes to hypercapnia under either hyperoxic or hypoxic conditions than nonperiodic breathers (2.98 +/- 0.72 vs. 1.50 +/- 0.39 l.min-1.Torr-1; 4.39 +/- 2.05 vs. 1.72 +/- 0.86 l.min-1.Torr-1; for both, P less than 0.04) and greater ventilatory responsiveness to hypoxia at a PCO2 of 46.5 Torr (2.07 +/- 0.91 vs. 0.87 +/- 0.38 l.min-1.% fall in SaO2(-1); P less than 0.04). To assess whether spontaneous oscillations in ventilation contributed to periodic breathing, power spectrum analysis was used to detect significant cyclic patterns in ventilation during NREM sleep. Oscillations occurred more frequently in periodic breathers, and hypercapnic responses were higher in subjects with oscillations than those without. The results suggest that spontaneous oscillations in ventilation are common during sleep and can be converted to periodic breathing with apnea when loop gain is increased.

Adult↗

Correlated and uncorrelated high-frequency oscillations in phrenic and recurrent laryngeal neurograms.

1. Power spectral analysis of phrenic and recurrent laryngeal (or efferent vagal) inspiratory discharge activity from anesthetized cats revealed a peak within the 60- to 110-Hz range in all spectra, plus a peak within the 40- to 60-Hz range in the laryngeal (and efferent vagal) spectra, and a peak less than 40 Hz in the phrenic spectra. 2. A 60- to 110-Hz peak was present in coherence spectra between the left and right phrenic neurograms, the left and right recurrent laryngeal (and efferent vagal) neurograms, and all combinations of phrenic-laryngeal (and phrenic-efferent vagal) pairs. It is concluded that the nearly-periodic oscillations represented by these peaks arise from a single source that projects functionally in parallel to many respiratory motor outputs. This source may be part of, or interact with, respiratory central pattern generation. 3. The 40- to 60-Hz oscillations in left and right recurrent laryngeal (and efferent vagal) neurograms were uncorrelated or occasionally were very weakly correlated. Thus it is unlikely that these oscillations arise from a common source such as a second respiratory central pattern generator. 4. The oscillations less than 40 Hz were weakly correlated between left and right phrenic neurograms. This correlation may be due substantially to spinal crossed-phrenic pathways. 5. It is proposed that both the 40- to 60-Hz oscillations in recurrent laryngeal neurograms and the oscillations below 40 Hz in phrenic neurograms originate in neural circuits associated with individual left or right recurrent laryngeal or phrenic motor outputs. 6. Our results do not support the interpretation that multiple peaks in phrenic and recurrent laryngeal power spectra are due to two respiratory central pattern generators whose outputs have parallel pathways to respiratory motoneurons.

Action Potentials↗

Central chemoreceptors.

When all peripheral chemoreceptors are denervated, animals continue to show increased ventilation when made to breathe CO2, indicating that receptors within the brain ("central chemoreceptors") are excited by acidity or changes in CO2. No cells have been identified within the brain that are indisputedly chemoreceptors for CO2 or H+, but there is abundant evidence that respiration can be affected by chemical, electrical, and thermal stimuli applied locally to the ventral surface of the medulla. Furthermore, the actions of traditional central chemical respiratory stimuli can be blunted or abolished after inhibition of neural function within this ventrolateral medullary shell (VMS). The VMS is an integrative region for cardiovascular and respiratory function and may be involved in nociception. The distinction between the former two is not always clear, but recent studies using microinjection techniques seem promising for identifying the respiratory substrates. The many recent advances elucidating anatomic connections between the VMS and other brain regions are important but do not directly address the question of the site of central respiratory chemosensitivity. Knowledge of such connections, however, should provide more definitive opportunities for addressing this question.

Animals↗

Control of laryngeal muscle activity in preterm infants.

Control of upper airway muscles, such as those in the larynx, appears important for optimizing airflow patterns during normal respiration. Electromyograms (EMGs) of the laryngeal (LAR) area and diaphragm (DIA) were recorded with esophageal and skin electrodes, respectively, in 12 unsedated sleeping preterm infants during changes in chemical and mechanical feedback. Onset of phasic inspiratory LAR EMG preceded both DIA EMG and inspiratory airflow by 70 +/- 60 and 180 +/- 80 ms, respectively. Inhalation of 4% CO2 increased both peak LAR and DIA EMGs but did not alter their temporal relationships. End expiratory occlusion prolonged both LAR (600 +/- 120 to 930 +/- 290 ms, p less than 0.05) and DIA EMGs (690 +/- 180 to 940 +/- 270 ms, p less than 0.005) as well as mechanical inspiratory time. Early braking of expiratory flow was accompanied by persistence of DIA EMG into the expiratory phase, while termination of mid- to late expiratory braking was associated with onset of the LAR EMG of the subsequent inspiration. We conclude that respiratory activity of the LAR EMG is altered by both chemical and mechanoreceptor stimulation. Furthermore, simultaneous recording of LAR and DIA EMGs suggests that upper airway and chest wall muscles have different effects on expiratory flow patterns in human infants.

Administration, Inhalation↗

High-frequency oscillations in human electromyograms during voluntary contractions.

Spectral analysis was used to identify correlated sinusoidal frequency components in left and right side diaphragm electromyographic (EMG) recordings from human subjects during voluntary deep inspirations. In 31 of 33 subjects bilaterally correlated high-frequency oscillations were found in broad or narrow bands in the range of 60-84 and 16-40 Hz. To determine if such oscillations were associated also with bilaterally symmetric, phasic, voluntary activation of nonrespiratory muscles, we obtained EMG signals from left and right masseter muscles during clenching of the jaw; left and right sternomastoid muscles during lifting of the head against gravity; and left and right biceps muscles during lifting of a weighted bar. Weakly correlated frequency components, mainly at frequencies below 60 Hz, were found in the left and right masseter EMGs on at least one trial from 12 of 17 subjects. No bilaterally correlated frequency components were found during phasic contraction of biceps and sternomastoid muscles. Power spectra of biceps EMGs, however, sometimes exhibited peaks indicative of oscillations that were not bilaterally correlated. In nine subjects, correlated frequency components in the 60-84 Hz range were found in intercostal EMGs from the axillary region of the fifth interspace during voluntary deep inspirations but not during postural contractions. We conclude that high-frequency oscillations in the range of 60-84 Hz in diaphragm and intercostal EMGs are associated particularly with respiratory activation of respiratory muscles. These results support the hypothesis that high-frequency oscillations may be a manifestation of control of muscular contraction via a central pattern generator.

Adult↗

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↗

Biphasic response of respiratory frequency to hypercapnea in preterm infants.

The time course of the transient ventilatory response to a sudden change in inspired gas from room air to 4% CO2 in air was examined in 11 healthy preterm neonates. Changes in minute ventilation (VI), tidal volume (VT), and respiratory frequency (f) were determined over 4 to 5 min of CO2 inhalation during both quiet (QS) and active sleep (AS) in each infant. In both states there was a brisk increase of mean VI in response to 4% CO2, while mean VT increased more slowly and mean f only increased transiently at 1 to 2 min. Exponential curve fitting to the change in VI and VT for each infant accounted for 64 +/- 20% of the variance in VI during QS as compared to 30 +/- 18% during AS (p less than 0.003). In only six infants did exponential curves fitted to the changes in VI and VT during QS reach 90% of their steady state values within 4 to 5 min of CO2 exposure. Their time to reach 90% of steady state was always shorter for VI than VT (p less than 0.01). Frequency showed a biphasic response with a transient rise at 1 to 2 min (p less than 0.05) and return to control levels at steady state. These data indicate that not all preterm infants reach a new level of steady state ventilation within 4 to 5 min of 4% CO2 inhalation. Furthermore, many infants exhibit a biphasic response of f over time which causes VI to reach steady state prior to VT.

Carbon Dioxide↗

Action of nicotine on the respiratory activity of the diaphragm and genioglossus muscles and the nerves that innervate them.

Nicotine is known to alter respiration by stimulating peripheral chemoreceptors and receptors within the brain. In this study the sites of action and the effects of nicotine on hypoglossal nerve activity were compared to its effects on phrenic activity in paralyzed, vagotomized and chloralose-anesthetized cats. Since anesthesia is known to affect respiratory responses, we also compared the effects of intravenous nicotine given to conscious unsedated cats on genioglossus and diaphragm electrical activity. In eight conscious animals intravenous doses of nicotine ranging between 10 ng and 200 micrograms increased genioglossus activity significantly more than diaphragm activity. Studies in 26 anesthetized animals included injection of nicotine, intravenously, in the lateral ventricles, and application of nicotine to the ventrolateral surface of the medulla (the putative site of the central chemoreceptors) before and after section of the carotid sinus nerves. With all these interventions, changes in hypoglossal nerve activity were significantly greater than changes in phrenic nerve activity. The responses to nicotine could be blocked by application of hexamethonium to the ventrolateral medullary surface or by cooling the same area. The results indicate that: nicotine increases hypoglossal nerve activity by both its peripheral and central effects; nicotine has differential effects on different respiratory muscles and nerves; and the central action of nicotine may be mediated largely through receptors located near the ventral medullary surface.

Anesthesia↗

Hypoglossal and phrenic responses to cholinergic agents applied to ventral medullary surface.

Application of cholinergic agents on the ventrolateral surface of the medulla in areas in which the "central chemoreceptors" are believed to be located stimulates breathing. It is also known that cranial nerves, such as the hypoglossal, have respiratory modulated activity (greater in inspiration than expiration) that responds to many of the same stimuli which affect breathing. In the present study we compared effects of cholinergic agents (acetylcholine, carbachol, methacholine, eserine) directly applied to chemoreceptive areas on the ventral medullary surface on phrenic and hypoglossal nerve activity. Studies were performed in paralyzed, anesthetized, and artificially ventilated cats after vagotomy. All cholinergic agents increased hypoglossal activity significantly more than phrenic activity in animals ventilated with O2 or 7% CO2 in O2 whether or not the carotid sinus nerves were intact. Atropine applied topically to the same medullary area blocked the respiratory effects of locally administered acetylcholine. The results suggest that cholinergic agents applied centrally can increase both phrenic and hypoglossal activity. Moreover the effects of the drugs are relatively greater on XII nerve activity than on phrenic discharge, suggesting that the drive from medullary cholinergic structures is distributed with unequal weight to different respiratory motoneurons.

Acetylcholine↗

Phasic volume-related feedback on upper airway muscle activity.

The effects of vagally mediated volume-related feedback on the activity of upper airway muscles was assessed in nine pentobarbital-anesthetized, tracheostomized, spontaneously breathing dogs. Moving average electrical activity was recorded before and during single-breath airway occlusions from the genioglossus, posterior cricoarytenoid, and alae nasi muscles and compared with simultaneously recorded tidal volume and electrical activity of the phrenic nerve (6 dogs) or diaphragm (3 dogs). The normally early peak of upper airway muscle activity during unoccluded breaths was delayed to late or end inspiration during occluded breaths. Inspiratory depression started at a lower volume above end-expiratory volume and at an earlier time after inspiratory onset for the upper airway muscles than for the phrenic nerve and the diaphragm. The amount of depression at the end of inspiratory airflow was larger for all of the upper airway muscles than for the phrenic nerve and diaphragm. Depressive effects were most prominent in the genioglossus, followed by the posterior cricoarytenoid and the alae nasi. After vagotomy, depressive effects of volume-related feedback were no longer seen. These results suggest that activity of the upper airway muscles is modulated by vagally mediated feedback, apparently to a larger extent than that of the diaphragm and phrenic nerve.

Animals↗

Bilaterally synchronized oscillations in human diaphragm and intercostal EMGs during spontaneous breathing.

Bilaterally synchronized high-frequency oscillations have been found in recordings of human diaphragm and intercostal EMGs during spontaneous breathing (SB). Correlated frequencies (28-52 and/or 68-88 Hz) in the left and right diaphragm EMGs during SB: (1) are at similar values, but not as broad-band, as those found during voluntary breathing maneuvers; (2) often occur at the same values as correlated frequencies found in left and right intercostal EMGs; and (3) fluctuate with time.

Adult↗

High-frequency oscillations in human respiratory electromyograms during voluntary breathing.

Electromyograms (EMGs) from respiratory muscles were obtained from human subjects during voluntarily controlled breathing. In 10 studies on 6 subjects EMGs were recorded from the right and left lower ventrolateral surface of the rib cage while the subject emphasized the use of his diaphragm for breathing. Simultaneous samples of the 2 EMG signals of 256-ms duration were obtained once per inspiration (in either the first of second half of inspiration) from each of 30 consecutive breaths using a laboratory minicomputer. Individual power spectra for the 2 EMG signals, and the squared coherence spectrum between them, were calculated. From the coherence spectrum common high-frequency oscillations could be identified within two frequency ranges: 70-100 Hz and 20-50 Hz. Peaks at similar frequencies were identified in both early-inspiratory and late-inspiratory EMG signals. Similar experiments were done on 3 subjects from whom an esophageal diaphragm EMG was obtained as well. The coherence spectrum between the esophageal EMG and the right rib cage surface EMG again demonstrated the presence of common high-frequency oscillations in the same frequency ranges as above. Evidence of these oscillations was not usually apparent in the power spectra. When ECG signal components were allowed to contaminate some of the EMG data samples, the coherence spectrum could be altered considerably, leading to inappropriate conclusions regarding the presence or absence of high-frequency oscillations. It is hypothesized that these high-frequency oscillations are similar to those described in nerve recordings from previous studies on anesthetized and decerebrate cats and dogs and a mechanism for their expression in EMG signals is proposed. The coherence spectrum is a very sensitive method for detecting related signal components in two signals. That high-frequency oscillations can be detected using the less sensitive techniques of autocorrelation and power spectral analysis in some animal preparations may reflect an enhancement of these oscillations in those preparations.

Decerebrate State↗

Transient ventilatory response to CO2 as a function of sleep state in full-term infants.

The influence of sleep state on the transient (i.e., initial 60 s) and steady-state ventilatory responses to 2% CO2 inhalation was studied in 19 healthy full-term infants. A nasal mask pneumotachometer was used to measure ventilation and end-tidal CO2 partial pressure (PCO2) and enabled abrupt changes in the inspired gas concentration to be made. The magnitude of the change in minute ventilation for both the transient and steady-state responses to CO2 was not statistically different between active (AS) and quiet (QS) sleep. Nonetheless the greater variability in minute ventilation during AS compared with QS continued throughout the period of CO2 inhalation and was associated with a more variable change in ventilation in the individual infants during AS. There was a greater increase in end-tidal PCO2 over the first 60 s during AS (3.3 +/- 0.3 vs. 2.6 +/- 0.2 Torr, in AS and QS, respectively, P less than 0.03). This may indicate a smaller initial increase in alveolar ventilation, relative to CO2 delivery to the lungs, in response to CO2 inhalation during AS. Asynchronous chest wall movements were more common during AS than QS (P less than 0.005) and did not change with CO2. The inconsistent transient ventilatory response to CO2 during AS compared with QS may be important in the behavior of infants to spontaneous episodes of hypercapnia occurring during AS.

Carbon Dioxide↗

Effect of sleep state and hypercapnia on alae nasi and diaphragm EMGs in preterm infants.

A coordinated activation of upper airway and chest wall muscles may be crucial in maintaining airway patency and ventilation. The alae nasi (AN) and diaphragm (DIA) electromyograms (EMG) were recorded with surface electrodes in 17 unsedated healthy preterm infants during both active (AS) and quiet sleep (QS). Airflow was measured via a nasal mask pneumotachograph and integrated to obtain tidal volume. Studies were performed during inhalation of room air and mixtures of 2 and 4% CO2 in air. In room air, phasic AN EMG accompanied 45 +/- 7% of breaths during AS compared with 14 +/- 5% of breaths during QS (P less than 0.001); however, with inhalation of 4% CO2 the incidence of AN EMG increased to comparable levels in both sleep states. During room air breathing onset of AN EMG preceded that of the DIA EMG and inspiratory airflow by 41 +/- 8 ms (P less than 0.01) and 114 +/- 29 ms (P less than 0.05), respectively. Peak AN activity preceded peak DIA activity by 191 +/- 36 ms (P less than 0.01). Alteration in sleep state or increasing chemical drive did not significantly alter these temporal relationships. Nevertheless, with each increase in end-tidal CO2, peak DIA EMG and tidal volume increased while peak AN EMG only showed a consistent increase during 4% CO2 inhalation. We conclude that although there exists a mechanism that temporally coordinates AN and DIA activation, the amount of AN EMG activity with each breath is not clearly correlated with DIA activation, which may contribute to the high incidence of respiratory dysrhythmias in preterm neonates.

Diaphragm↗

Alae nasi activation (nasal flaring) decreases nasal resistance in preterm infants.

The effect of alae nasi activation on nasal resistance in a group of healthy preterm infants was measured. Alae nasi activity was determined via the alae nasi electromyogram obtained from skin surface electrodes during both active and quiet sleep. Nasal resistance was calculated from airflow measured with a mask pneumotachograph and transnasal pressure drop obtained by simultaneous measurement of nasal pressure via a catheter inserted in one nostril and mask pressure. The percentage of breaths accompanied by phasic alae nasi activity was higher during active sleep than during quiet sleep (43% +/- 10% v 14% +/- 6%; P less than .005), and hypercapnic stimulation (4% CO2 inhalation) significantly increased the incidence of phasic alae nasi activity to comparable levels in both sleep states (82% +/- 8% in active sleep and 82% +/- 9% in quiet sleep). Elevation of tonic alae nasi activity also occurred more frequently during active sleep (P less than .05). The presence of either phasic or elevated tonic alae nasi activity decreased nasal resistance by 23% +/- 4% during active sleep and 21% +/- 3% during quiet sleep. This reduction in nasal resistance resulted in either a lower transnasal pressure during inspiration, a higher peak inspiratory airflow, or a combination of the two. Alae nasi activity may be an important mechanism that facilitates ventilation by reducing nasal resistance, and it may help stabilize the upper airway by preventing the development of large negative pharyngeal pressure during inspiration.

Airway Obstruction↗

Bilateral reflex effects on phrenic nerve activity in response to single-shock vagal stimulation.

The bilateral reflex actions of vagus nerve afferent signals on phrenic efferent activity have been tested by unilateral graded single shock electrical stimulation. An early excitation (latency 3-5 msec) was more prominent in the phrenic nerve contralateral to the stimulated vagus. Spinal cord hemisection at C3 eliminated both contralateral and ipsilateral responses: thus, both were mediated via descending tracts in the contralateral cord. A bilaterally symmetrical early inhibition (latency 8-12 msec) followed the early excitation. The electrical thresholds for evoking the early responses and the temperature for blocking these responses during graded vagal cooling were closely similar to the threshold and blocking temperature for pulmonary stretch receptor afferents. Higher stimulus strengths evoked a strong, bilaterally similar, late excitation (latency 12-20 msec) followed by a late inhibition. At very high stimulus strengths a third excitation (latency 25-30 msec) could appear. Sometimes these responses were followed by lowered phrenic activity for the remainder of inspiration. Single shock stimulation of the intact vagus nerve or of the peripheral end of the cut recurrent laryngeal nerve provoked, by the contraction of laryngeal muscles, a strong, short latency (12 msec) inhibition of phrenic activity mediated by superior laryngeal nerve afferents. The implications of these results with respect to the reflex pathways of the different responses and their possible integration in the central respiratory control mechanisms are discussed.

Afferent Pathways↗

Central and peripheral chemoreceptor inputs to phrenic and hypoglossal motoneurons.

We tested the hypothesis that phrenic and hypoglossal responses to progressive hypercapnia differ qualitatively because the CO2-related drive inputs to their respective motoneuron pools are different. The relative contributions of carotid sinus and central chemoreceptor inputs to hypoglossal and phrenic responses during hyperoxic hypercapnia were determined by comparing the two nerve activities during rebreathing runs done either before and after bilateral carotid sinus nerve (CSN) section, or without and with cooling of the intermediate, I(s), area on the ventral surface of the medulla. The studies were performed on chloralose-anesthetized, vagotomized, paralyzed cats. Cooling of the I(s) area impaired phrenic responsiveness to hypercapnia more than hypoglossal responsiveness, whereas CSN section had the opposite effect. Thus phrenic nerve response was more dependent on central chemoreceptor input than was the hypoglossal response, but hypoglossal response was more dependent on carotid sinus chemoreceptor input. We conclude that the phrenic and hypoglossal motoneuron pools each receive a different functional input from both the medullary and the carotid sinus chemoreceptors.

Action Potentials↗