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Biomedical subjects

N S Cherniack

Publications and source records attributed to N S Cherniack.

At least 19 recordsLinked to original sources
PubMed1992

Salivary secretion elicited by activation of the parabrachial nuclei in the cat.

The lateral pontine tegmentum contains the parabrachial nuclei (NPB) which have been identified as a relay nucleus for cardiovascular, respiratory and gustatory systems, but their role in the regulation of these systems is not well understood. We examined the effects of electrical and chemical stimulation of the NPB on blood pressure, phrenic and hypoglossal nerve activity and salivary secretion. These variables were measured in eight anesthetized (alpha-chloralose/urethane, 30/150 mg/kg, n = 5) or decerebrate (n = 3) cats before, during, and after trains of electrical stimulation (1 ms pulse duration, 10 Hz 5 min train duration, currents as low as 10 microA) delivered unilaterally to NPB. Stimulation of the NPB elicited copious salivary secretion (1100 +/- 270 mg, mean +/- S.D.; P less than 0.001). Secretion was blocked completely by prior administration of atropine. The effects of the stimulus train on the respiratory and cardiovascular systems were variable and inconsistent even though short-latency responses of phrenic and hypoglossal nerve activities to single pulses were consistent. The short-latency response of phrenic nerve activity was biphasic, a decrease followed by an increase in activity; the response of hypoglossal nerve activity was monophasic, a transient increase in activity. Effects of electrical stimulation were replicated by the injection of an excitatory amino acid agonist (kainic acid) into the dorsolateral pons. Injection of 50 nl of 10 mM kainic acid into the NPB evoked salivary secretion, indicating that this response was elicited by stimulation of cell bodies in the region. In addition, chemical excitation increased breathing frequency, peak phrenic nerve activity, and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cardiorespiratory changes induced by vertebral artery injection of sodium cyanide in cats.

Brain stem hypoxia caused by vertebral artery injection of sodium cyanide (NaCN) (1-20 micrograms) in artificially ventilated cats depressed phrenic and stimulated sympathetic nerve activity with a simultaneous increase in arterial blood pressure. Larger doses of NaCN caused greater effects. Hypercapnia produced by inhalation of 7% CO2 in O2 tended to reduce NaCN-induced responses on phrenic activity but not on blood pressure or sympathetic activity. Infusion into the vertebral artery with hypoxic saline (3% CO2 in N2) altered blood pressure, also affecting phrenic and sympathetic nerves similarly to NaCN administration. However, washout of CO2 by infusion of 100% O2 bubbled saline at high flow rates (3.6 ml/min) depressed phrenic as well as sympathetic activity and blood pressure. Spinal transection at the first cervical level eliminated sympathetic excitatory response to intravertebral cyanide injection. However, a large dose of NaCN (600 micrograms) given intravenously in spinal animal excited sympathetic activity. We conclude that intravertebral injection of NaCN can be used to study the effects of local hypoxia of the brain stem on cardiorespiratory responses and that hypoxia acts at both these sites (brain stem and spinal cord) to stimulate sympathetic excitation.

Animals↗
PubMed1992

Nonvagal modulation of hypoglossal neural activity.

Upper airway dilating muscle activity is characterized by an early-peaking pattern which serves to dilate or stiffen the upper airway at the time when the greatest negative intraluminal pressure is generated by contraction of chest wall muscles. This pattern has been attributed to phasic afferent inputs from pulmonary stretch receptors. The present study examines the hypothesis that nonvagal factors may also influence the discharge pattern and coordination of upper airway and chest wall muscle activities. Therefore, in anesthetized, paralyzed, vagotomized and artificially ventilated cats, we examined the effects of changes in respiratory drive produced by activation of cholinergic and GA-BAergic (gamma-aminobutyric acid) receptors at the ventrolateral aspects of the medulla oblongata on phasic intrabreath discharge patterns of hypoglossal and phrenic nerves. Cholinergic agents (acetylcholine, carbachol, methacholine, physostigmine) applied directly to chemoreceptive areas on the ventral medullary surface increased hypoglossal activity, and in addition converted inspiratory discharge from an augmenting to a decrementing pattern of activity. The reverse effect on the discharge pattern of hypoglossal activity was observed with a decrease in respiratory drive. While the amplitude of the phrenic nerve discharge was also affected by these interventions, the augmenting discharge pattern of phrenic nerve activity did not change. These results suggest that the early peaking pattern of hypoglossal nerve discharge in vagotomized cats also depends on the level of respiratory drive, and is not solely dependent on vagal afferent inputs. In addition, the data suggest that structures near the ventral surface of the medulla are influential in shaping the pattern of hypoglossal nerve activity and maintaining balanced activity of upper airway and chest wall muscles.

Acetylcholine↗
PubMed1991

Alteration of phrenic high frequency oscillation by local cooling of the ventral medullary surface.

Cooling of small sites on the ventral medullary surface of the cat produces a decrease in frequency of phrenic high frequency oscillation (HFO). The effect on HFO frequency of cooling near the hypoglossal rootlets, but not the effect of cooling near the inferior cerebellar artery, can be completely offset by raising arterial pCO2 to restore phrenic activity to its precooling level. Thus, structures near the ventral medullary surface are important for generation or propagation of phrenic HFO. The effect of cooling of the 'intermediate area' cannot be entirely explained as depression of putative central chemoreceptor activity.

Animals↗
PubMed1991

Sensation and control of breathing: a dynamic model.

A dynamic model of the CO2 respiratory control system is proposed, which can provide a qualitative basis for predicting breathing sensations. The discomfort index, which represents breathing sensations, is assumed to be composed of two sources: the arterial CO2 level and the respiratory motor command. The respiratory controller receives inhibitory neuromechanical and excitatory CO2 signals from the plant. The CO2 signal is enhanced by exercise stimuli. This dynamic multiplicative-type controller is used in simulations of key experiments: exercise and CO2 rebreathing with and without resistive loading. The dynamics of the discomfort index, the respiratory motor command, ventilation, and arterial CO2 concentration conform to the experimental data. The perceptual sensitivity to CO2 relative to respiratory effort is significantly correlated with the slope of hypercapnic ventilatory response. This result shows a clear linkage between ventilatory response and breathing sensations. Although it is shown that the automatic controller effectively minimizes the discomfort index for perturbations about an operating point under certain conditions, the discomfort index itself does not seem to be an underlying control principle of the proposed automatic controller model. Rather, breathing sensations may influence ventilatory responses by modifying the output of the automatic controller.

Carbon Dioxide↗
PubMed1991

Role of alpha 2-adrenergic receptors in the carotid body response to isocapnic hypoxia.

Alpha-2 adrenergic receptors have been identified in numerous tissues containing norepinephrine. Carotid bodies are sensory organs that detect changes in partial pressure of arterial oxygen and contain substantial amounts of norepinephrine. However, neither the presence nor the functional significance of alpha 2-receptors in the carotid body is known. The purpose of the present study was two-fold: (1) to determine the alpha 2-receptor density in the carotid body and (2) to assess their participation in the chemoreceptor responses to hypoxia. Experiments were performed on 27 anesthetized, paralyzed and artificially ventilated cats. Alpha-2 receptor binding determined by [125I]p-iodoclonidine averaged 10 +/- 2 fmol/mg of protein (n = 18 carotid bodies). Intracarotid infusion of an alpha 2-agonist (guanabenz; 0.5, 1, and 5 micrograms/min for 5 min) caused a dose-dependent depression of the baseline activity and 5 micrograms/min reduced the magnitude of the chemoreceptor response to isocapnic hypoxia by 61% (n = 8). Systemic administration of an alpha 2-antagonist (SKF-86466, 0.5-2 mg/kg) prevented the effects of guanabenz on the chemoreceptor activity. Furthermore, alpha 2-antagonist (0.5-2 mg/kg, i.v.) alone significantly increased baseline discharge by 68% and potentiated the chemoreceptor response to isocapnic hypoxia by 46% (n = 10). These results demonstrate that (1) alpha 2-adrenergic receptors are present in the carotid body and (2) they exert an inhibitory influence on chemoreceptor response to hypoxia. It is suggested that norepinephrine may tune the carotid body responses to hypoxia in part by its action on alpha 2-receptors.

Action Potentials↗
PubMed1991

Central effects of tachykinin peptide on tracheal secretion.

Tachykinin peptides acting on structures located on the ventral surface of the medulla can increase cholinergic outflow to the tracheal smooth muscles and augment respiratory motor output. In the experiments reported here (performed in anesthetized, paralyzed and artificially ventilated dogs), we examined the effects of tachykinin peptides substance P on secretion from submucosal glands. Changes in secretion were measured in an exposed section of tantalum-coated tracheal epithelium. Substances P was administered intracisternally or applied topically on the intermediate area of the ventral surface of medulla (VMS). Intracisternal infusion and the local medullary administration of tachykinin peptide caused a significant increase in tracheal submucosal gland secretion. Atropine given intravenously prevented the secretory changes induced by central action of tachykinins. In addition, prior application of 2% lidocaine to the medullary surface blocked the responses caused by substance P locally applied on the VMS. These findings suggest that substances P acting centrally can tracheal fluid secretion mainly via cholinergic mechanisms, and that the ventral surface of the medulla is one of the site of these action.

Amino Acid Sequence↗
PubMed1991

Influence of ventrolateral surface of medulla on tracheal gland secretion.

Airway secretion can be modified reflexly as well as locally. Previous studies indicate that neurons in a circumscribed region near the ventral surface of the medulla (VMS) can substantially modify airway tone and reflex responses to vagal inputs. In the present studies we assessed the importance of these neurons on tracheal gland secretion. We examined the changes in the number of hillocks of secretion appearing from submucosal glands in an exposed field of tracheal epithelium (1.2 cm2) coated with tantalum dust before and after interventions on the VMS. Experiments were performed in alpha-chloralose-anesthetized dogs paralyzed and ventilated with 40% O2. Stimulation of nicotinergic receptors by application of a pledget containing nicotine in 11 dogs caused a significant elevation in tracheal gland secretion in the subsequent 60 s, compared with a control period in which buffered saline was applied. Prior application of lidocaine or hexamethonium bromide to the VMS blocked the effect of topically applied nicotine. The central effects of nicotine were diminished by atropine methylnitrate given intravenously. In addition, lidocaine application to the VMS or focal cooling of intermediate areas to between 20 and 15 degrees C significantly decreased secretion rates reflexly produced by capsaicin-induced stimulation of pulmonary C-fiber receptors and by mechanical stimulation of the carina and larynx. These findings suggest that the ventral medulla contains cells near its surface that influence tracheal fluid secretion and modulate reflex responses of airway submucosal glands, probably by altering the level of general excitation within the central respiratory integrating circuits.

Animals↗
PubMed1991

Reflex responses of laryngeal and pharyngeal submucosal glands in dogs.

In dogs tracheal secretion is enhanced reflexly and by locally acting mediators such as substance P (SP). To evaluate the role of these mechanisms on submucosal gland secretion in the larynx (L) and pharynx (Ph), we compared the effects of mechanical stimulation of intrapulmonary irritant receptors and stimulation of pulmonary C-fiber receptors by capsaicin (20 micrograms/kg iv) with the response produced by intravenous SP. In six alpha-chloralose-anesthetized, paralyzed, and artificially ventilated dogs, submucosal gland secretion was monitored by analyzing the areas covered by hillocks of liquid and calculating the volume of secreted liquid (microliter) in the L and Ph. Mechanical stimulation of the carina increased both the number of hillocks and the volume of secreted liquid in the L. Excitation of pulmonary C-fiber receptors also increased the number of hillocks, and total volume of secreted liquid was elevated from 1.9 +/- 0.5 to 8.3 +/- 1.4 microliters (P less than 0.01). These responses were significantly reduced by prior cervical vagotomy and intravenous administration of atropine. Neither stimulation of irritant receptors nor stimulation of pulmonary C-fiber receptors caused discernible effects on Ph submucosal gland secretion. However, intravenous SP increased the number of Ph hillocks and elevated the volume of secreted Ph liquid from 1.0 +/- 0.6 to 10.2 +/- 1 microliters (P less than 0.01); similar responses to intravenous SP were observed in the L. Prior intravenous administration of atropine methylnitrate or bilateral vagotomy did not alter Ph or L secretory responses to intravenous SP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Occurrence of neutral endopeptidase activity in the cat carotid body and its significance in chemoreception.

The carotid body contains both tachykinins and enkephalins. Neutral endopeptidase (NEP, E.C. 3.4.24.11), has been suggested to involve in the metabolism of these neuropeptides in several organs. In the present study we determined neutral endopeptidase activity of the cat carotid body and assessed its significance in chemoreception. The cytosolic and membrane fractions of the carotid body contained NEP-like activity whereas it occurred only in the membrane fractions of the superior cervical and the nodose ganglia. Phosphoramidon, thiorphan and metal ion chelators inhibited NEP-like activity of all the 3 tissues studied; other protease inhibitors, however, were ineffective. Close carotid body administration of phosphoramidon significantly potentiated the carotid body response to low PO2 but not to hypercapnia. The enhanced response to hypoxia following phosphoramidon was further augmented by naloxone, an enkephalin antagonist. These results demonstrate that the glomus tissue contains detectable amounts of NEP-like activity and its inhibition selectively affects the hypoxic response of the carotid body.

Animals↗
PubMed1990

Effect of adenosine on isolated and superfused cat carotid body activity.

Adenosine is known to increase carotid chemoreceptor discharge in vivo. Since adenosine has powerful vascular effects it is possible that this chemoexcitation is indirectly caused by changes in carotid body blood flow. To evaluate this possibility the effect of adenosine (0.02-2.0 mumol) was assessed on the chemoreceptor activity of the cat carotid bodies in vitro. All three doses of adenosine produced an increase in chemoreceptor discharge which reached its maximum within 10-20 s and subsequently returned to preinjection controls within 1 min. The chemoreceptor excitation caused by adenosine was dose-dependent. These results suggest that adenosine induces chemoexcitation without changes in blood pressure and blood flow.

Action Potentials↗
PubMed1990

Effects of focal cooling in the ventrolateral medulla on chemoresponsiveness in dogs.

Studies in cats and dogs have shown that the ventrolateral region of the medulla participates significantly in the shaping of the respiratory rhythm. The purpose of this study was to examine the effects of unilateral focal cooling (15-20 degrees C) in the ventrolateral medullary region on respiratory responses to hypercapnia and hypoxia in dogs. A cryoprobe was used to cool selected locations in the ventrolateral medulla in 9 anesthetized and vagotomized dogs. Diaphragmatic electromyogram (EMG) was measured with implanted electrodes. The animals were ventilated artificially at a constant rate with 100% O2 and the inspired gas was switched to 7% CO2 in O2 or 10% O2 in N2 to determine the response to hypercapnia or hypoxia. The sites cooled ranged 4.0-8.0 mm rostral to obex, 3.0-5.5 mm lateral to midline, and within 1.5 mm deep from the ventral surface of the medulla. Unilateral focal cooling in this region significantly decreased the responses of both the amplitude and the rate of rise of diaphragmatic EMG to hypercapnia and hypoxia. These results support the hypothesis that neural structures in the ventrolateral medulla are important in the respiratory responses to hypoxia and hypercapnia as well as for the setting of respiratory drive and timing.

Animals↗
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↗