Biomedical subjects

N S Cherniack

Publications and source records attributed to N S Cherniack.

At least 109 records · Page 6Linked to original sources

PubMed1987

Respiratory and vasomotor effects of excitatory amino acid on ventral medullary surface.

Three glutamic acid analogues, N-methyl-D-aspartic (NMDA), quisqualic (QQ), and kainic (KAI) acids were applied topically to the ventral surface of the medulla (VMS) in paralyzed, vagotomized and carotid sinus denervated cats hyperventilated to apnea. Respiratory and vasomotor effects were assessed by changes in phrenic nerve activity and systemic arterial blood pressure. All three agents to varying degrees raised systemic blood pressure, but only NMDA consistently initiated phrenic nerve activity at pCO2 levels below that observed in control trials. KAI and QQ raised blood pressure even in those animals in which they had little effect on initiating phrenic nerve activity. Furthermore, respiratory responses were obtained from localized areas on VMS, namely the intermedio-caudal zone (I-C areas); whereas blood pressure elevations could be obtained from wider VMS areas including the rostral zone (R areas). In addition, the effects of the three amino acids on blood pressure were quantitatively different with KAI causing much greater increases in blood pressure than QQ or NMDA. The respiratory and vasomotor effects of NMDA and QQ were blocked by the use of 2-amino-5-phosphonovaleric acid and L-glutamic acid diethylester, their respective antagonists. The results suggest that neurons in the VMS which cause respiratory and vasomotor responses are not identical. Cells containing receptors stimulated by NMDA predominantly increase respiration, whereas cells containing receptors excited by KAI are more effective in eliciting vasomotor responses.

2-Amino-5-phosphonovalerate↗

PubMed1987

Aging effects on the interaction of hypercapnia and hypoxia as ventilatory stimuli.

We measured ventilatory responses to progressive hypercapnia at two steady-state levels of oxygenation and to progressive hypoxia at two steady-state levels of CO2 in 10 elderly and 10 young individuals. Under hyperoxic conditions, the ventilatory response to progressive hypercapnia was not significantly different between age groups but, under hypoxic conditions, the response to hypercapnia was lower in the elderly group. The interaction of hypercapnic and hypoxic stimuli was greater among young persons as indicated by a higher ratio of the hypercapnic response slopes (hypoxic/hyperoxic); 1.48 +/- 0.19 versus 0.98 +/- 0.11, p less than .05. The ventilatory response to hypoxia at the lower CO2 level was significantly greater among elderly than among young adults but not significantly different between age groups at the higher CO2 level. The ratio of hypoxic response slopes (high PCO2/lower PCO2) was 1.56 +/- 0.17 among elderly participants and 3.14 +/- 0.63 among young participants (p less than .05). These results suggest that aging diminishes the multiplicative effect of hypercapnia and hypoxia as ventilatory stimuli.

Adult↗

PubMed1987

Role of the vagal afferents in substance P-induced respiratory responses in anaesthetized rabbits.

Since substance P (SP)-like immunoreactivity has been demonstrated in vagal sensory fibres of bronchopulmonary origin, it was considered of interest to (1) characterize the pattern of responses to SP injected into the pulmonary as well as the systemic arterial system, and (2) assess the types of vagal afferents that are affected by SP. Experiments were performed on 15 pentobarbital-anaesthetized, spontaneously breathing rabbits. Efferent phrenic nerve activity was monitored as an index of central respiratory neural output. Intra-atrial injections of SP into the pulmonary circulation (100 ng kg-1) increased the respiratory rate, and peak integrated phrenic amplitude by 47 +/- 8 and 40 +/- 4%, respectively, above the controls. In addition, SP elicited augmented breaths (ABs) within 2-3 s in 67% of the trials. In contrast to right atrial injections, no ABs and no significant changes in respiratory rate were observed in response to intra-aortic injections of SP (100 ng kg-1). Tidal phrenic activity rise after aortic injections of SP was significantly less as compared with right atrial administrations of SP. Since both routes of administration decreased the arterial blood pressure to the same extent, these respiratory responses were not likely secondary to cardiovascular changes. After administration of an SP antagonist (D-Arg-D-Trp7,9, Leu11, SP), respiratory responses to SP were significantly attenuated. Also, the rate of occurrence of ABs elicited by releasing the tracheal occlusions was reduced (control 95 vs. 14% SP antagonist). Bilateral vagotomy abolished the tachypnoeic response and reduced the magnitude of the phrenic nerve increments caused by right atrial injection of SP.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed1987

Ventral medullary surface inputs to cervical sympathetic respiratory oscillations.

To examine the effects of focally cooling three areas (rostral, intermediate, and caudal) of the ventral medullary surface (VMS) on respiratory oscillations in cervical sympathetic and phrenic nerve activity, 12 cats were anesthetized, vagotomized, paralyzed, and artificially ventilated with 7% CO2 in O2. Cooling the intermediate area from 37 to 20 degrees C significantly reduced the magnitude of respiratory oscillations in both cervical sympathetic activity (P less than 0.001) and phrenic activity (P less than 0.001). Graded cooling of all three areas caused graded reductions in sympathetic respiratory-related activity that were comparable to the reductions in phrenic activity. The magnitude of the reductions in sympathetic respiratory oscillations was greatest for the intermediate area, followed in order by the caudal and rostral areas. Eight cats also underwent graded VMS cooling while ventilated with 3% CO2 in O2 and 100% O2. At each level of inspired CO2, graded cooling resulted in graded reductions in respiratory oscillations in sympathetic activity; conversely, at each medullary temperature, graded increases in inspired CO2 caused graded increases in cervical sympathetic respiratory activity. These results suggest that all three areas of the VMS influence respiratory oscillations in cervical sympathetic activity, although to different extents.

Animals↗

PubMed1987

A role for the ventral surface of the medulla in regulation of nasal resistance.

Nasal resistance is known to be affected by changes in nasal blood volume and hence to depend on sympathetic discharge to nasal blood vessels. Structures located superficially near the ventrolateral surface of the medulla significantly affect respiratory and sympathetic activity and the tone of the trachea. To assess the importance of these structures on nasal patency, we measured transnasal pressure at a constant flow and examined the change in pressure produced by topically applied N-methyl-D-aspartic acid (NMDA). Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. NMDA administered on the intermediate area of the ventral surface of the medulla decreased transnasal pressure and increased phrenic nerve activity. The response to NMDA could be diminished or abolished by application to the ventral medullary surface of the NMDA antagonist 2-amino-5-phosphonovalerate (2-APV) or the local anesthetic lidocaine. Carotid sinus denervation and posthypothalamic decerebration did not alter the nasal and phrenic nerve responses to NMDA; however, cervical sympathetic denervation decreased these responses, both in intact and in bilaterally adrenalectomized animals. Therefore, activation of NMDA receptors on structures near the ventral surface of the medulla increases tone in the nasal vasculature and leads to a response pattern that includes changes in not only phrenic nerve activity and blood pressure but also nasal patency.

2-Amino-5-phosphonovalerate↗

PubMed1987

Effects of bronchoconstriction on respiratory muscle activity during expiration.

The effect of methacholine-induced bronchoconstriction on the electrical activity of respiratory muscles during expiration was studied in 12 anesthetized spontaneously breathing dogs. Before and after aerosols of methacholine, diaphragm, parasternal intercostal, internal intercostal, and external oblique electromyograms were recorded during 100% O2 breathing and CO2 rebreathing. While breathing 100% O2, five dogs showed prolonged electrical activity of the diaphragm and parasternal intercostals in early expiration, postinspiratory inspiratory activity (PIIA). Aerosols of methacholine increased pulmonary resistance, decreased tidal volume, and elevated arterial PCO2. During bronchoconstriction, when PCO2 was varied by CO2 rebreathing, PIIA was shorter at low levels of PCO2, and external oblique and internal intercostal were higher at all levels of PCO2. Vagotomy shortened PIIA in dogs with prolonged PIIA. After vagotomy, methacholine had no effects on PIIA but continued to increase external oblique and internal intercostal activity at all levels of PCO2. These findings indicate that bronchoconstriction influences PIIA through a vagal reflex but augments expiratory activity, at least in part, by extravagal mechanisms.

Animals↗

PubMed1987

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↗

PubMed1987

Mechanical function of hyoid muscles during spontaneous breathing in cats.

We assessed the mechanical behavior of the geniohyoid and sternohyoid muscles during spontaneous breathing using sonomicrometry in anesthetized cats. When the animals breathed O2, the hyoid muscles either became longer or did not change length (but never shortened) during inspiration. During progressive hyperoxic hypercapnia, transient increases in geniohyoid muscle inspiratory lengthening occurred in many animals; however, at high PCO2 the geniohyoid invariably shortened during inspiration (mean 4.9% of resting length at the end of CO2 rebreathing; P less than 0.001). The PCO2 at which geniohyoid inspiratory lengthening changed to inspiratory shortening was significantly higher than the CO2 threshold for the onset of geniohyoid electrical activity (P less than 0.01). For the sternohyoid muscle, hypercapnia caused inspiratory lengthening in 13 of 17 cats and inspiratory shortening in 4 of 17 cats; on average the sternohyoid lengthened by 1.6% of resting length at the end of CO2 rebreathing (P less than 0.01). Sternohyoid lengthening occurred in spite of this muscle being electrically active. These results suggest that the relationship between hyoid muscle electrical activity and respiratory changes in length is very complex, so that the presence of hyoid muscle electrical activity does not necessarily indicate muscle shortening, and among the geniohyoid and sternohyoid muscles, the geniohyoid has a primary role as a hypopharyngeal dilator in the spontaneously breathing cat, with the sternohyoid muscle acting in an accessory capacity.

Animals↗

PubMed1987

Respiratory changes in thoracic muscle length during bronchoconstriction.

The purpose of the present study was to assess the effects of bronchoconstriction on respiratory changes in length of the costal diaphragm and the parasternal intercostal muscles. Ten dogs were anesthetized with pentobarbital sodium and tracheostomized. Respiratory changes in muscle length were measured using sonomicrometry, and electromyograms were recorded with bipolar fine-wire electrodes. Administration of histamine aerosols increased pulmonary resistance from 6.4 to 14.5 cmH2O X l-1 X s, caused reductions in inspiratory and expiratory times, and decreased tidal volume. The peak and rate of rise of respiratory muscle electromyogram (EMG) activity increased significantly after histamine administration. Despite these increases, bronchoconstriction reduced diaphragm inspiratory shortening in 9 of 10 dogs and reduced intercostal muscle inspiratory shortening in 7 of 10 animals. The decreases in respiratory muscle tidal shortening were less than the reductions in tidal volume. The mean velocity of diaphragm and intercostal muscle inspiratory shortening increased after histamine administration but to a smaller extent than the rate of rise of EMG activity. This resulted in significant reductions in the ratio of respiratory muscle velocity of shortening to the rate of rise of EMG activity after bronchoconstriction for both the costal diaphragm and the parasternal intercostal muscles. Bronchoconstriction changed muscle end-expiratory length in most animals, but for the group of animals this was statistically significant only for the diaphragm. These results suggest that impairments of diaphragm and parasternal intercostal inspiratory shortening occur after bronchoconstriction; the mechanisms involved include an increased load, a shortening of inspiratory time, and for the diaphragm possibly a reduction in resting length.

Animals↗

PubMed1987

Effect of N-methyl-D-aspartate applied to the ventral surface of the medulla on the trachea.

Structures located near the ventral surface of the medulla (VMS) affect both cardiovascular tone and respiratory activity. In addition cooling the intermediate area of the VMS blocks the increases in parasympathetic activity and tracheal tone resulting from ventilation with hypercapnic or hypoxic gas mixtures, or due to stimulation of mechanoreceptors within the lung. Since cooling the surface of the VMS may affect fibers of passage as well as cell bodies, we performed studies in which pledgets containing N-methyl-D-aspartic acid (NMDA), a synthetic excitatory amino acid, were applied to intermediate area of the VMS. The studies were performed in chloralose-anesthetized, artificially ventilated cats. Application of pledgets containing NMDA (10(-7) mol at 10(-3) M) caused increases in tracheal pressure and the onset of phasic phrenic activity, but application of 10(-8) mol at 10(-4) M of NMDA could produce tracheal constriction without the appearance of phasic phrenic activity. Applying to the entire VMS either 2-amino-5-phosphonovalerate (2-APV, 10(-6) M), a specific antagonist to NMDA, or lidocaine (2%), a local anesthetic, 60 s before the application of pledgets containing NMDA, prevented the increase in tracheal tone and phasic phrenic activity. Intravenous administration of atropine methyl nitrate 0.5 mg/kg, a cholinergic antagonist, blocked tracheal responses to local application of pledgets containing NMDA but did not affect the increase in phasic phrenic nerve activity. These findings suggest that when stimulated, neurons near the surface of the VMS in the vicinity of the intermediate area increase the activity of parasympathetic fibers to the airway.

Animals↗

PubMed1987

Relation between upper airway volume and hyoid muscle length.

Previous studies have suggested that the geniohyoid and sternohyoid muscles act to enlarge the upper airway. If correct, there should be an inverse relation between upper airway volume and the length of hyoid muscles. To test this, known volumes of air were injected into or removed from the isolated sealed upper airway of eight pentobarbital sodium-anesthetized cats, and the resultant changes in geniohyoid and sternohyoid length were measured using sonomicrometry. Increases in upper airway volume shortened the geniohyoid in all cats (P less than 0.001) and shortened the sternohyoid in seven of eight cats (P less than 0.01); mean geniohyoid shortening (as a % of resting length) exceeded that of the sternohyoid. Decreases in upper airway volume lengthened the geniohyoid in all cats (P less than 0.001) but caused variable changes in sternohyoid length. Extension of the neck increased the resting lengths of both the geniohyoid (P less than 0.001) and sternohyoid (P less than 0.002). Neck flexion shortened the resting length of both hyoid muscles (P less than 0.001 for both), with the geniohyoid shortening more (as a % of resting length) than the sternohyoid (P less than 0.005). Progressive flexion of the neck from 180 to 90 degrees caused progressive increases in the ratio of changes in muscle length to changes in upper airway volume during airway inflation but did not affect this relation during airway deflation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Effects of voluntary constraining of thoracic displacement during hypercapnia.

The study evaluated the interrelationships between the extent of thoracic movements and respiratory chemical drive in shaping the intensity of the sensation of dyspnea. Normal subjects rated their sensations of dyspnea as PCO2 increased during free rebreathing and during rebreathing while ventilation was voluntarily maintained at a constant base-line level. Another trial evaluated the effects on the intensity of dyspnea, of voluntary reduction in the level of ventilation while PCO2 was held constant. During rebreathing, there was a power function relationship between changes in PCO2 and the intensity of dyspnea. At a given PCO2, constraining tidal volume and breathing frequency to the prerebreathing base-line level resulted in an increase in dyspnea. The fractional differences in the intensity of dyspnea between free and constrained rebreathing were independent of PCO2. However, the absolute difference in the intensity of dyspnea between free and constrained rebreathing enlarged with increasing hypercapnia. At PCO2 of 50 Torr, this difference correlated significantly with the increase in both minute ventilation (r = 0.675) and tidal volume (r = 0.757) above the base line during free rebreathing. Similarly, during steady-state hypercapnia at 50 Torr PCO2, the intensity of dyspnea increased progressively as ventilation was voluntarily reduced from the spontaneously adopted free-breathing level. These results indicate that dyspnea increases with the level of respiratory chemical drive but that the intensity of the sensation is further accentuated when ventilation is constrained below that demanded by the level of chemical drive. This may be explained by a loss of inhibitory feedback from lung or chest wall mechanoreceptors acting on brain stem and/or cortical centers.

Adult↗

PubMed1987

Role of substance P in hypercapnic excitation of carotid chemoreceptors.

Experiments were performed on 17 anesthetized, paralyzed, and artificially ventilated cats to evaluate the importance of substance P-like peptide (SP) on the carotid body responses to CO2. Single or paucifiber carotid chemoreceptor activity was recorded from the peripheral end of the cut carotid sinus nerve. In eight of the cats the influence of SP on hyperoxic hypercapnic responses was studied. While the animals breathed 100% O2, intracarotid infusion of SP (1 microgram.kg-1.min-1, 3 min) increased chemoreceptor activity by +4.8 +/- 0.3 impulses/s. After SP infusion, inhalation of CO2 in O2 caused a rapid increase in activity that reached a peak and then adapted to a lower level, whereas similar levels of CO2 before SP caused only a gradual increase in carotid body discharge rate without any overshoot in response. Furthermore SP significantly increased the magnitude and slope of the CO2 response. In the other nine cats the effect of intracarotid infusion of an SP antagonist, [D-Pro2,D-Trp7,9] SP (10-15 micrograms.kg-1.min-1), on carotid body responses to 1) hyperoxic hypercapnia (7% CO2-93% O2), 2) isocapnic hypoxia (11% O2-89% N2), and 3) hypoxic hypercapnia (11% O2-7% CO2-82% N2) was examined. SP antagonist had no effect on carotid body response to hyperoxic hypercapnia but significantly attenuated the chemoreceptor excitation caused by isocapnic hypoxia and hypoxic hypercapnia. These results suggest that 1) SP may play an important role in carotid body responses to hypoxia but not to CO2, and 2) the mechanisms of stimulation of the carotid body by hypercapnia and by hypoxia differ.

Animals↗

PubMed1987

Effects of respiratory stimulation on alae nasi electromyograms and respiratory changes in length in dogs.

The relationship between the electrical and mechanical activity of the nasal dilator muscle was assessed in 8 pentobarbital-anesthetized, tracheostomized, supine dogs. Alae nasi electromyograms (EMGs) were recorded with bipolar fine wire electrodes, and respiratory changes in muscle length were recorded contralaterally using sonomicrometry. During both resting and stimulated breathing, the intrabreath pattern of muscle shortening closely paralleled the intrabreath pattern of EMG activity. Increases in both alae nasi EMG and alae nasi inspiratory shortening occurred in response to single-breath airway occlusions, brief periods of asphyxia, progressive hyperoxic hypercapnia, and intravenous nicotine sulfate administration. With all interventions, the increases in mechanical activation of the alae nasi paralleled the increases in alae nasi electrical activity. These results indicate that alae nasi EMGs, closely reflect respiratory changes in alae nasi length under conditions in which no mechanical load is placed in the nasal muscle.

Animals↗

PubMed1987

NHLBI workshop summary. Respiratory disorders of sleep. Pathophysiology, clinical implications, and therapeutic approaches.

The extensive investigation into complex interactions of breathing and sleep have produced answers to numerous important questions, but it is clear that many of the most important questions in this area remain unanswered. Our understanding of the mechanisms through which sleep alters breathing and how disordered breathing can, in turn, effect sleep is rudimentary. Although a large body of recent work has done much to elucidate the factors that act to maintain the patency of the upper airway during sleep, our understanding of such mechanisms and the relative importance of structure and function in this context remains primitive. A better understanding of these issues will be critical in elucidating the pathophysiology of respiratory disorders of sleep. Although some progress has been made in this area, new insights will be critically important to the design of novel, potentially more effective approaches to treatment. Therapeutic decisions are greatly hampered by major uncertainties regarding respiratory disorders of sleep and the clinical significance of symptoms, signs, and laboratory findings, and their relationship to morbidity and mortality. It seems clear that new information regarding the pathophysiology and natural history of these disorders will be important in the development of new, more effective strategies for therapeutic intervention, and this together with rigorous, systematic evaluation of new and future therapeutic approaches will be critical to clinical progress in this field.

Airway Resistance↗

PubMed1987

Reproducibility of ventilatory measurements during sleep on different nights in patients with chronic obstructive pulmonary disease.

To evaluate the reproducibility of respiratory measurements between nights we performed studies in 20 outpatients with stable, moderately severe chronic obstructive pulmonary disease. All patients had symptoms from their lung disease but had no sleep complaints. Their mean age was 61 years, mean 1-second forced expiratory volume was 42% of predicted, and mean functional residual capacity 195% of predicted. Arterial Pco2 averaged 40 +/- 1 (SEM) mm Hg and mean Po2 64 +/- 1 mm Hg. Sleep was monitored for 7 hours by standard techniques on 2 nights 1 week apart. Breathing was assessed by measuring airflow at the nose and mouth with thermistors, and rib cage and abdominal respiratory movements with inductive plethysmography. Oxygen saturation was measured with an ear oximeter. Patients slept on the average 58% of the time in the first night and 63% in the second. Arousals were common but apneas uncommon in both nights. There was no significant difference in median nocturnal O2 saturation on the 2 nights. Tidal volume and minute ventilation, but not respiratory rate, were significantly lower and more variable in rapid eye movement (REM) sleep as compared with wakefulness and non-REM sleep; however, mean values and the variance for tidal volume, respiratory rate, or minute ventilation were similar on both nights.

Aged↗

PubMed1987

Mechanisms of dyspnea.

An unpleasant sensation of difficulty in breathing is a common complaint in a variety of disease states. The psychophysical approach to the study of respiratory sensations has contributed greatly to the understanding of the mechanisms of dyspnea. Although dyspnea, in large part, is an expression of the sense of the effort of breathing, the intensity and quality of the subjective experiences during breathing are also dependent on afferent feedback primarily from receptors in the respiratory muscles. These inputs may act either by changing the level and pattern of respiratory motor activity or by a direct effect on higher brain centers. Finally, the expression of the symptoms of dyspnea in patients with cardiopulmonary disease is shaped by individual behavioral styles, personality, and emotional state. All of these factors must be taken into consideration in the management of the dyspneic patient.

Diaphragm↗

PubMed1986

Increased duration of postinspiratory inspiratory activity during augmented breaths in cats.

The duration of diaphragm electrical activity in augmented breaths during early expiration (postinspiratory inspiratory activity, PIIA) was assessed in 12 pentobarbital-anesthetized cats. There were significant prolongations of expiratory time (P less than 0.001) and PIIA (P less than 0.001) during augmented breaths compared to cupneic breaths, but no alteration in the portion of expiratory time during which the diaphragm was electrically silent. Furthermore, significant linear correlations were found between control and augmented breaths for the duration of PIIA (r = 0.95) and for the ratio of PIIA to expiratory time (r = 0.88). These results suggest that during augmented breaths there is not only an increased motor output to the diaphragm during inspiration, but that the early expiratory activity of the diaphragm is greater as well.

Animals↗