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Biomedical subjects

N S Cherniack

Publications and source records attributed to N S Cherniack.

At least 91 records · Page 5Linked to original sources
PubMed1988

Long-term effects of almitrine bismesylate on oxygenation during wakefulness and sleep in chronic obstructive pulmonary disease.

Hypoxemia in patients with chronic obstructive pulmonary disease (COPD) becomes more pronounced during sleep and can result in a number of serious consequences. Almitrine bismesylate is a peripheral chemoreceptor agonist that improves arterial oxygen tension (PaO2) in patients with COPD during wakefulness. Studies conducted for up to six months suggested the agonist may be useful in the management of nocturnal hypoxemia. In this double-blind, parallel, placebo-controlled study, patients with COPD received 50 mg of almitrine bismesylate (n = 9) or placebo (n = 11) twice a day for one year. Almitrine bismesylate increased PaO2 by 8.1 +/- 2.1 mm Hg (mean +/- SEM), decreased arterial carbon dioxide tension by 3.0 +/- 0.7 mm Hg (mean +/- SEM), and increased minute ventilation by 3.1 +/- 0.5 liters/minute (mean +/- SEM) during wakefulness. All of these changes were statistically significant. Five patients in the almitrine bismesylate group and eight patients in the placebo group completed sleep studies prior to and after 56, 180, and 360 days of almitrine bismesylate or placebo administration. Relative to placebo, almitrine bismesylate significantly increased oxygen saturation during sleep without any significant changes in the quantity or quality of sleep.

Adult↗
PubMed1988

Vagal influences on parasternal intercostal muscle inspiratory shortening during hypercapnia and airway occlusion.

To determine whether increases in electromyographic activity (EMG) are necessary for respiratory muscle shortening to occur during airway occlusion, respiratory changes in parasternal intercostal muscle length were measured using sonomicrometry in 11 anesthetized dogs during unoccluded (UB) and occluded (OB) breaths before and after vagotomy. During UB the extent of parasternal intercostal inspiratory shortening was greater after than before vagotomy both during oxygen breathing and during progressive hyperoxic hypercapnia. The relation between parasternal shortening, parasternal EMG, and tidal volume was not substantially affected by vagotomy. During OB parasternal intercostal EMG increased significantly compared to UB when the vagi were intact, but airway occlusion did not significantly change EMG activity post-vagotomy. However, both before and after vagotomy the parasternal intercostal shortened during OB in all animals. Parasternal intercostal inspiratory shortening during OB as a % of that during UB was significantly greater before compared to after vagotomy during oxygen breathing and moderate hypercapnia, but vagal integrity made no significant difference at high CO2. These results suggest that (1) pulmonary stretch receptor afferents inhibit parasternal intercostal inspiratory shortening but in proportion to their inhibitory effects on parasternal intercostal EMG and tidal volume, and (2) even when the EMG stays constant the parasternal intercostal muscle does not contract isometrically during occluded breaths.

Airway Obstruction↗
PubMed1988

Naloxone enhances the response to hypercapnia of spinal and cranial respiratory nerves.

To assess the effects of endogenous opiates on respiratory muscle responses to CO2, naloxone was administered intravenously to paralyzed, vagotomized and artificially ventilated cats anesthetized with alpha-chloralose. Neural activity was recorded from the phrenic, hypoglossal (HG), glossopharyngeal (GP) and recurrent laryngeal (RL) nerves. Before naloxone, phasic activity began first in the phrenic at a PETCO2 of 30.0 +/- 1.8 Torr, followed by the RL at a PETCO2 of 33.5 +/- 1.7 Torr, the HG at a PETCO2 of 39.9 +/- 2.1 Torr and the GP at a PETCO2 of 42.5 +/- 2.2 Torr during CO2 rebreathing. Naloxone had no significant effect on the apneic threshold of any of the nerves studied. Naloxone did, however, increase respiratory frequency (P less than 0.01) mainly by causing a significant (P less than 0.01) shortening of TE as it had no significant effect on TI. Naloxone also significantly increased the rate at which peak nerve activity increased with CO2 in the HG (P less than 0.01) and the GP (P less than 0.01) nerves, but not in the phrenic and RL nerves. Instead, the maximum activity produced by hypercapnia and the PETCO2 level at which maximum activity occurred in the phrenic, but not the RL, increased after naloxone. The result of these effects was that naloxone extended the range over which the HG and GP behaved proportionally with the phrenic, but it did not change the curvilinear nature of these relationships.

Animals↗
PubMed1988

Rate of elimination of excess CO2 in humans.

This study examined the ability of the respiratory system of awake normal subjects to correct an acute disturbance in body CO2 stores produced by rebreathing. Thirteen subjects, after 10 min of O2 breathing, rebreathed CO2 for 4 min in order to increase CO2 stores. The rate of CO2 elimination (VelCO2) after rebreathing was measured breath by breath for the next 10 min. The VelCO2 was highest immediately after the end of rebreathing and then decreased non-linearly toward the pre-rebreathing level as stored CO2 decreased. The time for 90% of this change in VelCO2 to occur (T90) was measured as an index of the rate of correction of body CO2 imbalance. The T90 was independent of the peak PCO2 obtained by rebreathing, and changes in CO2 storage did not produce significant changes in T90. The value of T90 was 120 +/- 48 sec (mean +/- SD) and there was a significant negative correlation between T90 and the slope of the ventilatory response to CO2 among subjects (r = -0.864, P less than 0.001). These results suggest that the capacity to eliminate the acutely stored CO2 in awake normal subjects is dependent on the ventilatory response to CO2. The data were further analyzed by using a mathematical model. Mathematical analysis confirmed the inverse relationship between CO2 sensitivity and T90. Model simulations also suggested that the restoration speed of CO2 balance under hyperoxic conditions is affected by brain blood flow but mainly determined by the sensitivity of central chemoreceptors.

Adult↗
PubMed1988

Inhibition of expiratory muscle EMG and motor unit activity during augmented breaths in cats.

To test the hypothesis that expiratory muscle activity is reduced during augmented breaths, electromyographic activity (EMG) of the triangularis sterni (TS) was recorded from eight pentobarbital anesthetized cats. Augmented breaths significantly increased tidal volume and peak diaphragm EMG, and prolonged inspiratory time and the first phase of expiration. However, the duration of the second phase of expiration was unchanged. Peak TS EMG was reduced during sighs in all animals, from 25 +/- 5 to 12 +/- 2 arbitrary units (P less than 0.005). Furthermore, the onset of TS activity during expiration was significantly delayed during augmented breaths (P less than 0.002), whereas the duration of expiratory firing tended to decrease but not significantly. Electrical activity was recorded from eight motor units of the TS in five cats. During resting breathing the motor units had a mean relative expiratory onset time of 46 +/- 4% of expiration, and a mean firing frequency of 19 +/- 2 impulses/sec. Two motor units became quiescent during augmented breaths. Of the remaining six motor units, three minimally shortened their duration of activity (by less than 15%) while three substantially abbreviated their period of firing (by 50% or more). In addition, all TS motor units reduced their mean firing frequency (P less than 0.05) and number of impulses per breath (P less than 0.002) during sighs. We conclude that expiratory activity of the triangularis sterni muscle is reduced during augmented breaths, due to a combination of motor unit derecruitment and a slowing of motor unit firing frequency.

Animals↗
PubMed1988

Respiratory and vasomotor responses to focal cooling of the ventral medullary surface (VMS) of the rat.

Experiments were performed on anesthetized, paralyzed and artificially ventilated rats after denervation of the vagus and carotid sinus nerves. The electrical activity of the phrenic and cervical sympathetic nerves (CS) along with the arterial blood pressure (BP) were monitored. Graded unilateral cooling of the ventral lateral surface (VMS) from 37 degrees C to 10 degrees C between 6th and 12th nerve rootlets did not affect the phrenic activity. Whereas, a significant depression or apnea was seen with cooling of an area between 1st cervical and 12th nerve rootlets. Bilateral cooling also produced similar respiratory responses. Respiratory depression could also be obtained during higher respiratory drive (7% CO2 in O2). On the other hand, a significant fall in BP and reduction in CS activity were observed with unilateral cooling in any of these VMS areas. However, the magnitude of BP decrease was less with 7% CO2 in O2 compared to 100% O2 breathing.

Animals↗
PubMed1988

Tracheal and phrenic responses to neurotensin applied to ventral medulla.

Respiratory activity and airway tone can be significantly affected by perturbations confined to superficial areas of the ventrolateral surface of the medulla (VMS). It is not clear which neuromediators are responsible for these changes. Neurotensin (NT), a tridecapeptide, fulfills many of the criteria required for a neurotransmitter or a neuromodulator. In this study, we determined whether NT applied topically to the intermediocaudal area of VMS could alter tracheal tone (Ptseg) and phrenic nerve activity (Ph) in alpha-chloralose-anesthetized cats hyperventilated with O2 to neural apnea. Also, the effects of NT on the responses of tracheal tone and phrenic nerve activity to steady-state hyperoxic hypercapnia (3% CO2 in O2) and isocapnic hypoxia (12% O2) were tested. Application of pledgets containing NT (10(-5)-10(-3) M) caused significant increases in Ptseg and Ph activity without significant changes in blood pressure. Both tracheal and phrenic responses to hypercapnia and hypoxia were also increased by an earlier application of NT. Application of lidocaine (2%) to the VMS rapidly reversed NT-induced responses and prevented them on reapplication of NT. Phosphoramidon, a neutral endopeptidase inhibitor, potentiated responses to NT, suggesting that a mechanism exists at the VMS that could reverse NT effects. Earlier topical administration of hexamethonium bromide to the VMS did not influence the effects of NT, indicating that NT was not acting by causing the release of acetylcholine. Intravenous administration of atropine (1 mg/kg) blocked tracheal but not phrenic responses to NT. These findings suggest that neurotensin may be a neuromodulator involved in central chemosensitivity and that it may participate in the regulation of phrenic activity and parasympathetic tone of airway smooth muscle.

Animals↗
PubMed1988

Transverse abdominis length changes during eupnea, hypercapnia, and airway occlusion.

The abdominal muscles accelerate airflow during expiration and may also influence the end-expiratory volume and configuration of the thorax. Although much is known about their electrical activity, the degree to which they change length during the respiratory cycle has not been previously assessed. In the present study we measured respiratory changes in transverse abdominis length using sonomicrometry in 14 pentobarbital sodium-anesthetized supine dogs and compared length changes to simultaneously recorded tidal volume and transverse abdominis electromyograms (EMG). To determine muscle resting length at passive functional residual capacity (LFRC), the animals were hyperventilated to apnea. The transverse abdominis was electrically active in all animals during resting O2 breathing (eupnea). During inspiration the transverse abdominis lengthened above resting length in all 14 dogs by a mean of 3.7 +/- 1.1% LFRC; during expiration the transverse abdominis shortened below resting length in 13 of 14 dogs by a mean of 4.2 +/- 0.9% LFRC. Increasing hyperoxic hypercapnia (produced in 9 animals) progressively heightened transverse abdominis EMG and progressively increased the extent of muscle shortening below resting length (to 12.6 +/- 3.2% LFRC at a PCO2 of 90 Torr). During single-breath airway occlusion substantial inspiratory lengthening of the transverse abdominis occurred, both during O2 breathing and during CO2 rebreathing.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1988

Rib cage and abdominal expiratory muscle responses to CO2 and esophageal distension.

The present study compared the responses of rib cage and abdominal expiratory muscles to chemical and mechanical stimuli. In pentobarbital-anesthetized spontaneously breathing dogs, electromyograms (EMG) were recorded from the triangularis sterni (TS) and transverse abdominis (TA) muscles using bipolar intramuscular wire electrodes. During resting oxygen breathing, both muscles were electrically active during expiration. Progressive hyperoxic hypercapnia significantly augmented the expiratory activity of both the TA and the TS. However, the mean percent increases in electrical activity in response to CO2 were substantially greater for the TA than for the TS at all PCO2 levels greater than 50 Torr (P less than 0.01). Occlusion of the airway at end inspiration significantly delayed the onset of TS EMG (from 0.35 +/- 0.07 to 3.35 +/- 0.67 sec; P less than 0.002) and decreased TS EMG rate of rise (P less than 0.002), but did not significantly alter these parameters for the TA. Esophageal distension increased TS EMG in all dogs (by mean of 220 +/- 64%; P less than 0.01), but in contrast decreased TA EMG in all dogs (by a mean of 63 +/- 12%; P less than 0.001). The response to esophageal distention occurred in a graded manner and appeared to be mediated predominantly via vagal afferents. We concluded that expiratory muscles of the rib cage and abdomen manifest substantial differences in their electrical responses to chemoreceptor, pulmonary stretch receptor, and esophageal mechanoreceptor stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1988

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↗
PubMed1988

Upper airway pressure receptors alter expiratory muscle EMG and motor unit firing.

To examine the effects of upper airway negative pressure (UAW NP) afferents on respiratory muscle activity during expiration (TE), diaphragm electromyograms (EMG) and triangularis sterni EMG and single motor unit activity were recorded from supine anesthetized tracheotomized cats while they breathed 100% O2. The period of TE during which the diaphragm was electrically active (TE-1) and the period of TE during which the diaphragm was quiescent (TE-2) were both increased with continuous UAW NP (P less than 0.001 and P less than 0.05, respectively), as was TE-1 as a percent of TE (P less than 0.001). Continuous UAW NP reduced peak triangularis sterni EMG (P less than 0.001) and delayed its expiratory onset (P less than 0.005) but did not alter its duration of firing. Changes in triangularis sterni EMG were due to a combination of complete cessation of motor unit activity (2 of 17 motor units), a reduction in mean motor unit firing frequency (P less than 0.02), and a delay in the expiratory onset of motor unit activity (P less than 0.001). Qualitatively similar results were obtained when UAW NP was applied during inspiration only. We conclude that 1) UAW NP has reciprocal stimulatory and inhibitory influences on diaphragm and triangularis sterni muscle electrical activity, respectively, during expiration, and 2) the reductions in triangularis sterni EMG are due to both motor unit derecruitment and a slowing of motor unit firing frequency.

Animals↗
PubMed1988

Effect of stimulation of pulmonary C-fiber receptors on canine respiratory muscles.

The effects of stimulation of pulmonary C-fiber receptors on the distribution of motor activity to upper airway, rib cage, and abdominal muscles were studied in anesthetized, tracheotomized, spontaneously breathing dogs. Stimulation of pulmonary C-fiber receptors by injection of capsaicin (3-20 micrograms/kg) into the right atrium resulted in complete cessation of electrical activity of the upper airway dilating muscles (UADM) and the inspiratory chest wall pumping muscles. The activity of abdominal muscles was also inhibited. The duration of electrical silence was longer for the diaphragm than for the UADM. Upper airway constricting muscles and expiratory intercostal muscles, including the triangularis sterni, remained tonically active during the apneic period. The responses of these muscles were qualitatively the same when the animals breathed 100% O2, 7% CO2 in O2, or 12% O2 in N2, and without or in the presence of an expiratory threshold load. Bilateral vagotomy abolished the inhibitory effects of capsaicin on UADM, chest wall, and abdominal muscle activity, suggesting that the vagus is the major afferent pathway for the reflex. The qualitative difference in the response of intercostal expiratory muscles and abdominal muscles suggests that these two groups of synergistic muscles may be independently regulated.

Animals↗
PubMed1988

Effects on respiratory pattern of focal cooling in the medulla of the dog.

Studies in cats have shown that, in addition to respiratory neuron groups in the dorsomedial (DRG) and ventrolateral (VRG) medulla, neural structures in the most ventral medullary regions are important for the maintenance of respiratory rhythm. The purpose of this study was to determine whether a similar superficially located ventral region was present in the dog and to assess the role of each of the other regions in the canine medulla important in the control of breathing, in 20 anesthetized, vagotomized, and artificially ventilated dogs, a cryoprobe was used to cool selected regions of the medulla to 15-20 degrees C. Respiratory output was determined from phrenic nerve or diaphragm electrical activity. Cooling in or near the nucleus of the solitary tract altered timing and produced little change in the amplitude or rate of rise of inspiratory activity; lengthening of inspiratory time was the most common timing effect observed. Cooling in ventrolateral regions affected the amplitude and rate of rise of respiratory activity. Depression of neural tidal volume and apnea could be produced by unilateral cooling in two ventrolateral regions: 1) near the nucleus ambiguus and nucleus para-ambiguus and 2) just beneath the ventral medullary surface. These findings indicate that in the dog dorsomedial neural structures influence respiratory timing, whereas more ventral structures are important to respiratory drive.

Animals↗
PubMed1988

Role of triangularis sterni during coughing and sneezing in dogs.

Studies in mammals have found that during breathing the triangularis sterni (TS) muscle regulates expiratory airflow and the end-expiratory position of the rib cage and furthermore that the respiratory activity of this muscle is influenced by a variety of chemical and mechanical stimuli. To assess the role of the TS during coughing and sneezing, electromyograms (EMGs) recorded from the TS were compared with EMGs of the transversus abdominis (TA) in eight pentobarbital-anesthetized dogs. During coughing induced by mechanically stimulating the trachea or larynx (n = 7 dogs), peak EMGs increased from 23 +/- 2 to 74 +/- 5 U (P less than 0.00002) for the TS and from 21 +/- 6 to 66 +/- 4 U (P less than 0.0002) for the TA. During sneezing induced by mechanically stimulating the nasal mucosa (n = 3 dogs), peak EMG of the TS increased from 10 +/- 3 to 66 +/- 7 U (P less than 0.005) and peak EMG of the TA increased from 10 +/- 2 to 73 +/- 7 U (P less than 0.02). For both muscles the shape of the EMG changed to an early peaking form during coughs and sneezes. Peak expiratory airflow during coughs of different intensity correlated more closely with peak TS EMG in three dogs and with peak TA EMG in four dogs; peak expiratory airflow during sneezes of different intensity correlated more closely with peak TS than TA EMG in all three animals. These results suggest that the TS is actively recruited during coughing and sneezing and that different neuromuscular strategies may be utilized to augment expiratory airflow.

Animals↗
PubMed1987

Comparison of the response of diaphragm and upper airway dilating muscle activity in sleeping cats.

The steady state and transient effects of hyperoxic hypercapnia on the electromyographic activities of the genioglossus (GG), posterior cricoarytenoid (PCA), and diaphragm (D) were studied in cats instrumented with chronically implanted electrodes during non-rapid eye movement sleep. Hypercapnia (inhalation of 3.4 and 7.4% CO2 in O2) increased the phasic electrical activity occurring during inspiration of all three muscles. Activities of the PCA and D increased in a parallel fashion with increasing CO2. The GG responded to steady state CO2 inhalation alinearly, with larger increases in activity occurring when CO2 was raised from 3.4 to 7.4% than when CO2 was increased from 0 to 3.4%. When gas mixtures containing CO2 were given, the GG reached its new steady state level more slowly than the D or PCA, and when CO2 was rapidly removed from the inspired gas mixture, the GG attained its steady state sooner than the D. These results suggest that in sleeping cats, hypercapnia does not affect either transient or steady state responses of the GG in the same way as the D or the PCA. These differences seem to be explained largely by different threshold characteristics of hypoglossal and phrenic neurons.

Animals↗
PubMed1987

Cooling the intermediate area of the ventral medullary surface affects tracheal responses to hypoxia.

The intermediate area of the ventral medullary surface (VMS) influences changes in airway tone caused by hypercapnia and intrapulmonary irritant receptor activation. These studies evaluated the effects of cooling the intermediate area of the VMS on the reflex hypoxic responses of the trachealis smooth muscle and of the phrenic nerve. Anesthetized, paralyzed cats were hyperventilated with 100% oxygen to produce phrenic neural apnea. Tracheal tone was measured indirectly by evaluating pressure changes in an innervated tracheal segment and the phrenic electroneurogram was determined from the central end of a cut cervical root. Switching the inspired gas to 12% O2 increased tracheal pressure of 11 of 12 cats but caused phrenic activity to reappear in only 6 of the animals. Ventilation with 6% O2 significantly increased tracheal constriction prior to phrenic activity. After intravenous administration of atropine methyl nitrate tracheal responses to hypoxia were abolished but phrenic neural responses were unaltered. Neither the tracheal pressure nor the phasic phrenic electroneurogram responded to hypoxia after cutting the carotid sinus nerves. When the intermediate area of the VMS was cooled to 20 degrees C prior to ventilation with the hypoxic gases, both tracheal and phrenic responses were significantly diminished. While the cats were hyperventilated with 6% O2, cooling of the intermediate area significantly diminished tracheal pressure and phrenic nerve activity and both returned to the same levels after rewarming. Cooling of the intermediate area blunted tracheal and phrenic responses to carotid body stimulation by NaCN. However, the appearance of tracheal constriction prior to the onset of phasic phrenic activity may suggest that increased trachealis tone may occur independent of cyclical respiratory activity.

Animals↗