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Biomedical subjects

N S Cherniack

Publications and source records attributed to N S Cherniack.

At least 73 records · Page 4Linked to original sources
PubMed1990

Sensation of dyspnea during hypercapnia, exercise, and voluntary hyperventilation.

To determine whether the intensity of dyspnea at a given level of respiratory motor output depends on the nature of the stimulus to ventilation, we compared the sensation of difficulty in breathing during progressive hypercapnia (HC) induced by rebreathing, during incremental exercise (E) on a cycle ergometer, and during isocapnic voluntary hyperventilation (IVH) in 16 normal subjects. The sensation of difficulty in breathing was rated at 30-s intervals by use of a visual analog scale. There were no differences in the level of ventilation or the base-line intensity of dyspnea before any of the interventions. The intensity of dyspnea grew linearly with increases in ventilation during HC [r = 0.98 +/- 0.02 (SD)], E (0.95 +/- 0.03), and IVH (0.95 +/- 0.06). The change in intensity of dyspnea produced by a given change in ventilation was significantly greater during HC [0.27 +/- 0.04 (SE)] than during E (0.12 +/- 0.02, P less than 0.01) and during HC (0.30 +/- 0.04) than during IVH (0.16 +/- 0.03, P less than 0.01). The difference in intensity of dyspnea between HC and E or HC and IVH increased as the difference in end-tidal PCO2 widened, even though the time course of the increase in ventilation was similar. No significant differences were measured in the intensity of dyspnea that occurred with changes in ventilation between E and IVH. These results indicate that under nearisocapnic conditions the sensation of dyspnea produced by a given level of ventilation seems not to depend on the method used to produce that level of ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of expiratory resistive loading on the sensation of dyspnea.

To determine whether an increase in expiratory motor output accentuates the sensation of dyspnea (difficulty in breathing), the following experiments were undertaken. Ten normal subjects, in a series of 2-min trials, breathed freely (level I) or maintained a target tidal volume equal to (level II) or twice the control (level III) at a breathing frequency of 15/min (similar to the control frequency) with an inspiratory load, an expiratory load, and without loads under hyperoxic normocapnia. In tests at levels II and III, end-expiratory lung volume was maintained at functional residual capacity. A linear resistance of 25 cmH2O.1(-1).s was used for both inspiratory and expiratory loading; peak mouth pressure (Pm) was measured, and the intensity of dyspnea (psi) was assessed with a visual analog scale. The sensation of dyspnea increased significantly with the magnitude of expiratory Pm during expiratory loading (level II: Pm = 9.4 +/- 1.5 (SE) cmH2O, psi = 1.26 +/- 0.35; level III: Pm = 20.3 +/- 2.8 cmH2O, psi = 2.22 +/- 0.48) and with inspiratory Pm during inspiratory loading (level II: Pm = 9.7 +/- 1.2 cmH2O, psi = 1.35 +/- 0.38; level III: Pm = 23.9 +/- 3.0 cmH2O, psi = 2.69 +/- 0.60). However, at each level of breathing, neither the intensity of dyspnea nor the magnitude of peak Pm during loading was different between inspiratory and expiratory loading. The augmentation of dyspnea during expiratory loading was not explained simply by increases in inspiratory activity. The results indicate that heightened expiratory as well as inspiratory motor output causes comparable increases in the sensation of difficulty in breathing.

Adult↗
PubMed1990

Stability analysis of CO2 control of ventilation.

A theoretical analysis of the CO2 control of the respiratory system is presented using both analytic and simulation techniques. A stability index (SI) is obtained by linearizing a dynamic first-order model with a time delay. Analytically, SI values greater than unity predict an unstable response to a disturbance. Because the first-order model is reduced from a higher-order physiological model, SI can be algebraically related to physiological parameters. This relationship shows that SI increases with a decrease in system tissue volume, metabolic rate, or inspired CO2 partial pressure; SI decreases with a decrease in time delay, cardiac output, controller gain, or controller intercept. Analytically, SI distinguishes stable from unstable domains. By simulations of the nonlinear first-order model, three domains are obtained: an unstable domain (sustained oscillations, SI greater than 1.1), an underdamped stable domain (transient oscillations, 0.3 less than SI less than 1.1), and an overdamped stable domain (no oscillations, 0 less than SI less than 0.3). With this classification, disturbances such as change of state (e.g., from awake to asleep) or sigh may produce transient oscillations if the system becomes underdamped even though stable. Potential applications of this work include quantitative distinction of the physiological factors in control disorders associated with short-term periodicities (e.g., Cheyne-Stokes breathing, sleep apnea, breathing at altitude).

Carbon Dioxide↗
PubMed1990

Effects of changes in level and pattern of breathing on the sensation of dyspnea.

Breathing during hypercapnia is determined by reflex mechanisms but may also be influenced by respiratory sensations. The present study examined the effects of voluntary changes in level and pattern of breathing on the sensation of dyspnea at a constant level of chemical drive. Studies were carried out in 15 normal male subjects during steady-state hypercapnia at an end-tidal PCO2 of 50 Torr. The intensity of dyspnea was rated on a Borg category scale. In one experiment (n = 8), the level of ventilation was increased or decreased from the spontaneously adopted level (Vspont). In another experiment (n = 9), the minute ventilation was maintained at the level spontaneously adopted at PCO2 of 50 Torr and breathing frequency was increased or decreased from the spontaneously adopted level (fspont) with reciprocal changes in tidal volume. The intensity of dyspnea (expressed as percentage of the spontaneous breathing level) correlated with ventilation (% Vspont) negatively at levels below Vspont (r = -0.70, P less than 0.001) and positively above Vspont (r = 0.80, P less than 0.001). At a constant level of ventilation, the intensity of dyspnea correlated with breathing frequency (% fspont) negatively at levels below fspont (r = -0.69, P less than 0.001) and positively at levels above fspont (r = 0.75, P less than 0.001). These results indicate that dyspnea intensifies when the level or pattern of breathing is voluntarily changed from the spontaneously adopted level. This is consistent with the possibility that ventilatory responses to changes in chemical drive may be regulated in part to minimize the sensations of respiratory effort and discomfort.

Adult↗
PubMed1990

Central action of tachykinins on activity of expiratory pumping muscles.

The central effects of tachykinins (substance P, neurokinin A, and neurokinin B) on the distribution of the motor activity to rib cage and abdominal expiratory muscles were studied in anesthetized tracheotomized spontaneously breathing dogs and cats. Intracisternal application of substance P (11 dogs) in doses of 10(-5) to 10(-4) M caused diaphragm electrical activity to change insignificantly from 19.3 +/- 1.9 to 24.8 +/- 3.2 units (P greater than 0.05), produced a moderate increase of triangularis sterni activity from 12.6 +/- 2.2 to 19.2 +/- 2.2 units (P less than 0.05), and stimulated a large increase of transversus abdominis activity from 9.4 +/- 2.7 to 28.5 +/- 2.6 units (P less than 0.01). Comparable effects were seen with similar doses of neurokinin A (8 dogs) and neurokinin B (3 dogs) administered intracisternally. Local application of substance P to the ventral medullary surface (5 dogs and 4 cats) also caused expiratory muscle activity to increase more than diaphragm activity, and in addition transversus abdominis activity increased to a larger extent than triangularis sterni activity. Furthermore, administration of the substance P antagonist [D-Pro2,D-Trp7,9]-SP to the ventral medullary surface decreased respiratory motor output, with expiratory muscles activity being attenuated to a greater extent than diaphragm activity. Application of neurotensin and N-methyl-D-asparate to the ventral surface of the medulla produced responses similar to those observed as a result of central administration of tachykinin peptides. The results suggest that 1) mammalian tachykinins are involved in the regulation of thoracic and abdominal expiratory muscle activity, 2) these muscles manifest substantial differences in their electrical responses to excitatory neuropeptides acting centrally, and 3) inputs from modulatory neurons located in this vicinity of the ventral medullary surface seem to be distributed unevenly to different expiratory premotor and/or motoneurons.

Animals↗
PubMed1989

Substance P and neurokinin A in the cat carotid body: localization, exogenous effects and changes in content in response to arterial pO2.

In the present work we studied the occurrence of substance P (SP) and neurokinin A (NKA) in the carotid bodies of cats by means of immunocytochemistry and radioimmunoassay (RIA). We also compared the exogenous effects of SP and NKA on carotid body sensory discharge. SP- and NKA-like immunoreactivities (SP-LI; NKA-LI) were seen in many glomus cells and in a sparse plexus of fine fibers. The SP-LI containing glomus cells and fibers also exhibited NKA-LI, suggesting that both these tachykinins coexist in the carotid body. Chemoreceptor discharge increased both by SP and NKA in a dose-dependent manner. The peak excitation produced by SP and NKA was the same when the effects were compared on an equimolar basis. The tachykinin content of the carotid bodies varied with changes in arterial pO2. During normoxia, SP and NKA levels were 57 +/- 8 and 85 +/- 14 fmol/mg, respectively. When the animals were exposed for 1 h to 100% O2, SP content was unchanged (51 +/- 4 fmol/mg), whereas NKA levels were significantly lower than during normoxia (29 +/- 3 fmol/mg, P less than 0.01). Following 1 h of hypoxia, SP content of the carotid body was 146 +/- 20 fmol/mg, a value higher than that obtained during normoxia and hyperoxia. NKA levels, on the other hand, were not significantly different from normoxic values. These results indicate that the cat carotid body (1) contains both SP and NKA, (2) both peptides augment neural discharge of the carotid body and (3) their levels in the carotid body are substantially altered by arterial oxygen, the natural stimulus to the chemoreceptors.

Action Potentials↗
PubMed1989

Factors affecting respiratory system stability.

Periodic breathing (recurrent central apneas) occurs frequently during sleep. Periodic breathing can arise as a result of unstable behavior of the respiratory control system. A mathematical model of the respiratory control system was used to investigate, systematically, the effect of severity of disturbances to respiration and certain system parameters on periodic breathing occurring during sleep. The model consisted of multi-compartment representation of O2 and CO2 stores, a peripheral controller sensitive to O2 and CO2, and a central controller sensitive to CO2. The effects of hypoxia and hypercapnia on the upper airway muscles were not considered in the model. Episodes of hyperventilation or asphyxia were used to disturb the control system and explore the boundaries of stable breathing. Circulation time and metabolic rate were also varied. Simulations with the model produced the following findings: The number of central apneas associated with periodic breathing were greater as circulation time increased; controller gain increases also made the number of apneas greater, although periodic breathing occurs with lower controller gains as circulation time increases. At each level of circulation time there was a range of controller gain changes which caused little change in the number of apneas. There were more apneas with hypoxia; also the number of apneas increased with sleep-associated reductions in metabolic rate. The more rapidly resting PCO2 rose at sleep onset, the greater the likelihood of recurrent apneas. Finally, the more intense the disturbance, the more apneas there were.

Chemoreceptor Cells↗
PubMed1989

Central modulatory effects of tachykinin peptides on airway tone.

Previous studies suggest that structures within 1 mm of the ventral surface of the medulla (VMS) are involved in the regulation of airway resistance. Furthermore, neurons containing tachykinin peptides have been observed near the surface of the VMS. In the present work, we examined the effects of mammalian tachykinins, substance P (SP) and neurokinin A (NKA), applied locally to the intermediate area of the VMS of cats on tracheal tone and phrenic nerve activity. Since neutral endopeptidase (enkephalinase) has been shown to degrade tachykinin peptides in other tissues, we also investigated the effect of the neutral endopeptidase (NEP) inhibitors (thiorphan and phosphoramidon) on airway tone and phrenic nerve responses to tachykinins when the animals were ventilated with 100% O2 and during hyperoxic hypercapnia and isocapnic hypoxia. Experiments were performed in chloralose-anesthetized cats hyperventilated to phrenic neural apnea or so that the end tidal CO2 was just above the apneic threshold. Trachealis smooth muscle tension was assessed by measuring changes in pressure in a balloon placed in a bypassed segment of trachea (Ptseg). Application to the VMS of SP (10(-5)-10(-3) M) significantly increased tracheal muscle tension. Similar effects were found with applications of NKA. In addition, thiorphan and phosphoramidon potentiated the effects of tachykinins and the responses to hypercapnia and hypoxia of tracheal tone and phrenic nerve activity. Pretreatment with atropine (1 mg/kg) blocked tracheal but not phrenic responses to tachykinins. These suggest that (1) tachykinins acting on structures located on the VMS can increase cholinergic outflow to the airways and augment respiratory motor output, and (2) NEP may be one important modulator of tachykinin-induced effects.

Airway Resistance↗
PubMed1989

Integration of cardiorespiratory responses in the ventrolateral medulla.

Interventions confined to the region adjacent to the VMS can produce both respiratory and circulatory effects. Although it has been suggested that both breathing and vasomotor changes arise from the same neural elements near the VMS, our own investigations indicate that the neurons involved are closely linked but not identical. This belief is supported by recent studies which show that AII and angiotensin antagonists microinjected into the rostral portion of the VMS can significantly modify blood pressure and respiration but can produce effects of different sign. These observations, coupled with previous studies of the VMS, indicate the possibility that regions near the VMS may contribute to integration of circulatory and respiratory responses.

Animals↗
PubMed1989

Role of the ventral surface of medulla in the generation of Mayer waves.

The regions adjacent to the ventrolateral medullary surface (VMS) play critical roles in the regulation of respiratory and cardiovascular function. Furthermore, these areas seem to be important sites for the integration of afferent inputs from certain sensory organs and the source of excitatory inputs to preganglionic sympathetic and parasympathetic neurons. To determine whether the VMS contributes to the generation of nonrespiratory-related periodic oscillations of arterial blood pressure (Mayer waves), excitatory substances, such as N-methyl-D-aspartate (NMDA), cholinergic agonists, and neuropeptides (substance P, neurokinin A, neurotensin), were applied topically to the intermediate area of VMS in anesthetized cats. In addition, the effects of application of lidocaine and inhibitory substances (benzodiazepines) on Mayer waves were studied. After application of excitatory substances to the VMS, we observed oscillations of arterial blood pressure, recurring with a period of 17.8 +/- 10 (SE) s, which had similar characteristics as the Mayer waves recorded during hypercapnia or hypoxia. In addition, cyclic changes in phrenic nerve activity and tracheal tone occurred with the same periodicity as arterial blood pressure oscillation. Application of lidocaine or benzodiazepines on the intermediate area of the VMS abolished Mayer waves observed during hypercapnia, hypoxia, or application of excitatory substances. These findings show for the first time that the VMS can be considered as one of several synaptic relays involved in the generation of arterial blood pressure oscillation, as well as the cyclic changes in phrenic nerve activity and tracheal smooth muscle tone that occur simultaneously.

Animals↗
PubMed1989

Benzodiazepines acting on ventral surface of medulla cause airway dilation.

The benzodiazepines that have anxiolytic, anticonvulsant, muscle-relaxant, and sedative-hypnotic properties affect respiration possibly by acting on gamma-aminobutyric acid (GABA)ergic receptors. This study investigated the effects of benzodiazepines diazepam and midazolam) applied topically to or microinjected just beneath the ventrolateral medullary surface (VMS) on airway tone in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats. Trachealis smooth muscle tension was assessed by measuring the changes in pressure in a balloon placed in a bypassed rostral segment of the trachea. In 21 cats ventilated with 7% CO2 in O2, surface application of benzodiazepines caused a significant decrease in tracheal tone. Similar to topical application, microinjection of midazolam (1 microgram) in the ventral medulla (0.1-0.2 mm from the surface) in six cats decreased tracheal pressure by 13.2 +/- 2.1 cmH2O (P less than 0.01). In addition, application of benzodiazepines on the VMS in animals ventilated with 12% O2 in N2 (n = 5) decreased tracheal pressure from 15.9 +/- 2.2 to 5.2 +/- 2.7 cmH2O (P less than 0.05). Furthermore, in all cats studied (n = 6), the magnitude of lung deflation-induced tracheal contraction was reduced after application of benzodiazepines on the ventral surface of the medulla (from 11.4 +/- 1.6 to 2.2 +/- 0.9 cmH2O; P less than 0.01). The effects of benzodiazepines on tracheal tone were reversed and blocked by application of Ro 15-1788, a specific benzodiazepines antagonist. However, when parasympathetic activity was abolished by atropine and tracheal tone was restored with 5-hydroxytryptamine, benzodiazepines applied on the VMS had no effect on tracheal pressure. These results suggest that benzodiazepines acting centrally, on structures located near the VMS, can cause a decrease in airway smooth muscle tone by diminishing the activity of parasympathetic neurons which project to the airways.

Animals↗
PubMed1989

Involvement of ventral medullary surface in respiratory responses induced by 2,4-dinitrophenol.

We examined the contribution of the neural elements near the ventral medullary surface (VMS) to the respiratory response caused by 2,4-dinitrophenol (DNP). Two series of experiments were performed on 12 vagotomized and sinoaortic denervated cats. The first series examined the effect of focal cooling of the VMS on the respiratory response to DNP in four spontaneously breathing, anesthetized cats. When the VMS temperature was 37 degrees C, systemic administration of DNP increased minute ventilation under nearly isocapnic conditions, and focal cooling of the intermediate area of VMS to 20 degrees C attenuated the ventilatory augmentation caused by DNP. To eliminate the influence of anesthetics, a second group of experiments was performed on eight decerebrate, artificially ventilated cats while phrenic nerve activity was monitored as an index of respiration. AgNO3 (10%) was topically applied to the VMS until the respiratory response to inhaled CO2 was abolished. Apnea occurred in seven of eight cats after AgNO3, whereas in the remaining one animal, tidal phrenic activity decreased substantially. Systemic administration of DNP produced no respiratory excitation in any of the animals. On the other hand, rhythmic respiratory activity could be provoked by electrical stimulation of the mesencephalic locomotor area and carotid sinus nerve and by excitation of somatic afferents. Histological examination of the brain stem showed that the AgNO3 had penetrated no more than 350 microns from the ventral medullary surface. These results indicate superficial structures of the VMS are of potential importance in mediating the respiratory responses to hypermetabolism.

2,4-Dinitrophenol↗
PubMed1989

Influence of respiratory drive on airway responses to excitation of lung C-fibers.

To determine whether the responses of tracheal smooth muscle and the nasal vasculature to stimulation of lung C-fiber receptors depend on the level of respiratory drive, the effects of right atrial injection of capsaicin and phenyldiguanide were studied in chloralose-anesthetized, paralyzed, artificially ventilated cats. Studies were performed while the animals were hyperventilated to apnea and, in addition, when breathing was stimulated by inhalation of 7% CO2 or by N-methyl-D-aspartic acid (NMDA) applied to the ventral surface of the medulla. When the cats were hyperventilated to apnea with O2, injection of capsaicin into the right atrium increased tracheal tone and slightly raised nasal resistance. However, when the animals were ventilated with 7% CO2 in O2 or respiratory activity was stimulated by the application of NMDA, administration of capsaicin eliminated spontaneous phrenic nerve activity and caused an abrupt decrease in tracheal tone but still increased nasal resistance. Similar responses were also obtained with right atrial injection of phenyldiguanide. These results showed for the first time that in the cat the direction of the reflex effects on tracheal tone but not nasal resistance depends on the preexisting level of respiratory drive and on cholinergic activity to airway smooth muscle.

Airway Resistance↗
PubMed1989

Respiratory effects of N-methyl-D-aspartate on the ventrolateral medullary surface.

We studied the central effects of N-methyl-D-aspartate (NMDA) on respiration in 18 artificially ventilated cats anesthetized with alpha-chloralose. Unilateral topical application of NMDA (1 x 10(-8) mol) to the intermediate region of the ventrolateral medulla exaggerates the phrenic response to CO2 at end-tidal PCO2 levels of less than 50.0 Torr. At higher end-tidal PCO2 levels, however, such differences disappear. Unilateral NMDA application increases the activity of the right and left phrenic nerves equally. Furthermore, the magnitude of the phrenic response after unilateral application of NMDA was not different from that after bilateral application. NMDA also had a vasopressor action when applied to the ventrolateral medullary surface. In contrast to respiratory responses, bilateral application of NMDA caused a significant increase in blood pressure compared with unilateral application of NMDA. Application of the NMDA antagonist 2-amino-5-phosphonovaleric acid abolished both the blood pressure and respiratory effects of NMDA. These results suggest that CO2 and NMDA may act on a common respiratory premotoneuron to produce stimulation of breathing. Because blood pressure responses, unlike respiratory responses, were greater after bilateral application than after unilateral application of NMDA, it is suggested that the neural substrates for the two effects of NMDA seem to be different.

2-Amino-5-phosphonovalerate↗
PubMed1989

Effects of tracheal airway occlusion on hyoid muscle length and upper airway volume.

Complex relationships exist among electromyograms (EMGs) of the upper airway muscles, respective changes in muscle length, and upper airway volume. To test the effects of preventing lung inflation on these relationships, recordings were made of EMGs and length changes of the geniohyoid (GH) and sternohyoid (SH) muscles as well as of tidal changes in upper airway volume in eight anesthetized cats. During resting breathing, tracheal airway occlusion tended to increase the inspiratory lengthening of GH and SH. In response to progressive hypercapnia, the GH eventually shortened during inspiration in all animals; the extent of muscle shortening was minimally augmented by airway occlusion despite substantial increases in EMGs. SH lengthened during inspiration in six of eight animals under hypercapnic conditions, and in these cats lengthening was greater during airway occlusion even though EMGs increased. Despite the above effects on SH and GH length, upper airway tidal volume was increased significantly by tracheal occlusion under hypercapnic conditions. These data suggest that the thoracic and upper airway muscle reflex effects of preventing lung inflation during inspiration act antagonistically on hyoid muscle length, but, because of the mechanical arrangement of the hyoid muscles relative to the airway and thorax, they act agonistically to augment tidal changes in upper airway volume. The augmentation of upper airway tidal volume may occur in part as a result of the effects of thoracic movements being passively transmitted through the hyoid muscles.

Airway Obstruction↗
PubMed1989

Responses of upper-airway dilating muscles and diaphragm activity to end-expiratory pressure loading in anesthetized dogs.

The steady-state responses of upper-airway dilating muscles and diaphragm activity to elevation of lung volume induced by positive end-expiratory pressure loading were studied in 9 pentobarbital-anesthetized dogs with vagus nerves intact. The early and late effects of 5 min of expiratory threshold loads upon upper airway dilating muscle activity (the alae nasi, the genioglossus and the posterior cricoarytenoid) were compared to their effects on diaphragm activity. During resting O2 breathing, application of 5 and 10 cm H2O of positive end-expiratory pressure produced no significant change in the peak electrical activity of the upper-airway dilating muscles and diaphragm (p greater than 0.05). No qualitative differences were found in the upper-airway dilating muscles and diaphragm responses to expiratory threshold loads when the animals breathed 3 or 7% CO2 in O2, compared to when they inspired 100% O2. Furthermore, no differences were found in the electrical activity of the upper-airway dilating muscles and diaphragm at any given end-tidal CO2 when unloaded responses were compared with loaded responses during progressive hypercapnia. However, positive end-expiratory pressure loading caused significant prolongation of expiratory duration, which gradually returned toward control levels when the loads were maintained. In animals who developed periodic breathing by increasing levels of anesthesia, positive end-expiratory pressure loading eliminated the periodicity and made the pattern of breathing regular. Based on these results, it can be concluded that under the conditions of these experiments, increases in lung volume produced by expiratory threshold loads do not reduce the activity of upper-airway dilating muscles. The maintenance of the electrical activity of the upper-airway dilating muscles might be caused by excitatory reflex mechanisms or central habituation.

Animals↗