Influence of the ventral surface of the medulla on tracheal responses to CO2

1986 ◽  
Vol 61 (3) ◽  
pp. 1091-1097 ◽  
Author(s):  
E. C. Deal ◽  
M. A. Haxhiu ◽  
M. P. Norcia ◽  
J. Mitra ◽  
N. S. Cherniack
Keyword(s):  
Motor Activity ◽  
Phrenic Nerve ◽  
Ventral Surface ◽  
Intermediate Area ◽  
Tracheal Pressure ◽  
Cervical Trachea ◽  
Airway Responses ◽  
Airway Tone ◽  
Pressure Changes ◽  
Nerve Discharge

These studies investigated the role of the intermediate area of the ventral surface of the medulla (VMS) in the tracheal constriction produced by hypercapnia. Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. Airway responses were assessed from pressure changes in a bypassed segment of the rostral cervical trachea. Hyperoxic hypercapnia increased tracheal pressure and phrenic nerve activity. Intravenous atropine pretreatment or vagotomy abolished the changes in tracheal pressure without affecting phrenic nerve discharge. Rapid cooling of the intermediate area reversed the tracheal constriction produced by hypercapnia. Graded cooling produced a progressive reduction in the changes in maximal tracheal pressure and phrenic nerve discharge responses caused by hypercapnia. Cooling the intermediate area to 20 degrees C significantly elevated the CO2 thresholds of both responses. These findings demonstrate that structures near the intermediate area of the VMS play a role in the neural cholinergic responses of the tracheal segment to CO2. It is possible that neurons or fibers in intermediate area influence the motor nuclei innervating the trachea. Alternatively, airway tone may be linked to respiratory motor activity so that medullary interventions that influence respiratory motor activity also alter bronchomotor tone.

Respiration during hypothermia: effect of rewarming intermediate areas of ventral medulla

1985 ◽  
Vol 59 (5) ◽  
pp. 1423-1427 ◽  
Author(s):  
J. P. Kiley ◽  
F. L. Eldridge ◽  
D. E. Millhorn
Keyword(s):  
Phrenic Nerve ◽  
Respiratory Activity ◽  
Ventral Surface ◽  
Respiratory Frequency ◽  
Independent Effect ◽  
Neural Function ◽  
Nerve Activity ◽  
Intermediate Area ◽  
Phrenic Nerve Activity ◽  
Significant Reversal

We studied respiration (phrenic nerve activity) during progressive hypothermia to as low as 30.5 degrees C in five anesthetized, paralyzed, glomectomized, and vagotomized cats. PCO2 was maintained at a constant level throughout the experiments. We confirmed the results of a previous study (J. P. Kiley, F. L. Eldridge, and D. E. Millhorn, J. Appl. Physiol. 58: 295–312, 1985) in which respiratory minute output decreased progressively with cooling and respiratory frequency decreased markedly. In addition we show that focal rewarming to normal temperature (37.5 degrees C) of the structures in the intermediate areas on the ventral surface of the medulla resulted in a significant reversal of the depressed respiratory minute activity observed with hypothermia. Respiratory frequency, however, was unaffected by intermediate area rewarming. We conclude that the decreased respiratory activity during hypothermia is due to a generalized interference with neural function. A major portion of these effects is due to cooling of the intermediate areas, but the slowing of respiratory frequency appears to be an independent effect.

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

1987 ◽  
Vol 63 (3) ◽  
pp. 1268-1274 ◽  
Author(s):  
M. A. Haxhiu ◽  
E. C. Deal ◽  
M. P. Norcia ◽  
E. van Lunteren ◽  
N. S. Cherniack
Keyword(s):  
Respiratory Activity ◽  
Excitatory Amino Acid ◽  
Ventral Surface ◽  
Intermediate Area ◽  
Cholinergic Antagonist ◽  
Tracheal Pressure ◽  
Area Increase ◽  
Specific Antagonist ◽  
Methyl Nitrate ◽  
Atropine Methyl Nitrate

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.

Spontaneous phrenic nerve activity in the exteriorized fetal lamb

1975 ◽  
Vol 39 (1) ◽  
pp. 124-128 ◽  
Author(s):  
I. Wyszogrodski ◽  
H. W. Taeusch ◽  
R. L. Williams
Keyword(s):  
Neural Activity ◽  
Phrenic Nerve ◽  
High Frequency ◽  
Single Unit ◽  
Nervous Activity ◽  
Nerve Activity ◽  
Phrenic Nerve Activity ◽  
Tracheal Pressure ◽  
Fetal Lamb ◽  
Pressure Changes

Phrenic nerve activity and tracheal pressure changes were recorded in four exteriorized fetal lambs (120–135 days gestation) from lightly anesthetized ewes to study possible mechanisms involved in the establishment of rhythmical breathing patterns. Two types of spontaneous neural activity were found. The first consisted of high-frequency multiunit bursts (mean duration 820 ms; range 450–2,500 ms) that preceded a gasp. Individual units within these bursts reached peak discharge frequencies as high as 40 impulses/s. The second type of neural activity consisted of single-unit, low-frequency (1–14 impulses/s), irregular background discharges lasting up to several seconds without changes in tracheal pressure. Occasionally, higher frequency bursts of single-unit activity were detected that were also unassociated with tracheal pressure changes. The data indicate that the neural correlate of a fetal gasp includes high-frequency synchronized bursting activity in the phrenic nerve. In addition, background phrenic activity can be detected in the exteriorized fetal lamb that reflects central nervous activity in the absence of tracheal pressure changes.

Electrical activity of phrenic nerve and diaphragm in utero

1975 ◽  
Vol 39 (4) ◽  
pp. 513-518 ◽  
Author(s):  
A. Bahoric ◽  
V. Chernick
Keyword(s):  
Phrenic Nerve ◽  
Total Duration ◽  
In Utero ◽  
Respiratory Center ◽  
Nerve Activity ◽  
Recording Time ◽  
Fetal Sheep ◽  
Phrenic Nerve Activity ◽  
Tracheal Pressure ◽  
Pressure Changes

Phrenic nerve activity, diaphragmatic EMG, and tracheal or pleural pressure changes were recorded in a chronic fetal sheep preparation. Three patterns of fetal phrenic nerve activity were observed: 1) a single burst; 2) irregular nonrhythmic bursts; and 3) prolonged rhythmic activity, seen only prior to fetal death. The total recording time was 54.53 h and the total duration of phrenic nerve activity was 65.34 min (2.16%). When an inactive period was defined as the absence of phrenic nerve activity for 60 s or more, active periods occupied 44.7% of the total time. Phrenic nerve activity was present in all fetuses and 97.5% of the time was coupled with diaphragmatic EMG. Both diaphragmatic EMG and intrapulmonary pressure changes occurred in the absence of phrenic nerve activity. In three fetal animals both phrenic nerves were transected. Tracheal pressure changes were seen which were not coupled with corresponding intrauterine pressure changes. Thus, changes in fetal tracheal pressure or diaphragmatic EMG do not necessarily represent the output of the fetal respiratory center. This study suggests that the fetal respiratory center is active in utero, but this activity is minimal and has a different pattern that that present after birth.

Influence of ventrolateral surface of medulla on reflex tracheal constriction

1986 ◽  
Vol 61 (2) ◽  
pp. 791-796 ◽  
Author(s):  
M. A. Haxhiu ◽  
E. C. Deal ◽  
M. P. Norcia ◽  
E. van Lunteren ◽  
J. Mitra ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Tone ◽  
Ventral Surface ◽  
Intermediate Area ◽  
Previous Level ◽  
Focal Cooling ◽  
Alpha Chloralose ◽  
Pressure Changes ◽  
Stimulation Of

To assess the role of structures located superficially near the ventrolateral surface of the medulla on the reflex constriction of tracheal smooth muscle that occurs when airway and pulmonary receptors are stimulated mechanically or chemically, experiments were conducted in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats. Pressure changes within a bypassed segment of the trachea were used as an index of alterations smooth muscle tone. The effects of focal cooling of the intermediate areas or topically applied lidocaine on the ventral surface of the medulla on the response of the trachea to mechanical and chemical stimulation of airway receptors were examined. Atropine abolished tracheal constriction induced by mechanical stimulation of the carina or aerosolized histamine, showing that the responses were mediated over vagal pathways. Moderate cooling of the intermediate area (20 degrees C) or local application of lidocaine significantly decreased the tracheal constrictive response to mechanical activation of airway receptors. Furthermore, when the trachea was constricted by histamine, cooling of the intermediate area significantly diminished the increased tracheal tone, whereas rewarming restored tracheal tone to the previous level. These findings suggest that under the conditions of the experiments the ventral surface of the medulla plays an important role in constriction of the trachea by inputs from intrapulmonary receptors and in the modulation of parasympathetic outflow to airway smooth muscle.

Benzodiazepines acting on ventral surface of medulla cause airway dilation

1989 ◽  
Vol 257 (4) ◽  
pp. R810-R815 ◽  
Author(s):  
M. A. Haxhiu ◽  
E. van Lunteren ◽  
N. S. Cherniack ◽  
E. C. Deal
Keyword(s):  
Smooth Muscle ◽  
Muscle Tone ◽  
Muscle Tension ◽  
Ventral Surface ◽  
Gamma Aminobutyric Acid ◽  
Tracheal Pressure ◽  
Parasympathetic Neurons ◽  
Lung Deflation ◽  
Airway Tone ◽  
Alpha Chloralose

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.

Respiratory Activity of the Rat Posterior Cricoarytenoid Muscle

1997 ◽  
Vol 106 (11) ◽  
pp. 897-901 ◽  
Author(s):  
Robert G. Berkowitz ◽  
John Chalmers ◽  
Qi-Jian Sun ◽  
Paul M. Pilowsky
Keyword(s):  
Phrenic Nerve ◽  
Muscle Activity ◽  
Electrophysiological Study ◽  
Emg Activity ◽  
Diaphragmatic Muscle ◽  
Posterior Cricoarytenoid Muscle ◽  
Inspiratory Activity ◽  
Intramuscular Nerve ◽  
Posterior Cricoarytenoid ◽  
Nerve Discharge

An anatomic and electrophysiological study of the rat posterior cricoarytenoid (PCA) muscle is described. The intramuscular nerve distribution of the PCA branch of the recurrent laryngeal nerve was demonstrated by a modified Sihler's stain. The nerve to the PCA was found to terminate in superior and inferior branches with a distribution that appeared to be confined to the PCA muscle. Electromyography (EMG) recordings of PCA muscle activity in anesthetized rats were obtained under stereotaxic control together with measurement of phrenic nerve discharge. A total of 151 recordings were made in 7 PCA muscles from 4 rats. Phasic inspiratory activity with a waveform similar to that of phrenic nerve discharge was found in 134 recordings, while a biphasic pattern with both inspiratory and post-inspiratory peaks was recorded from random sites within the PCA muscle on 17 occasions. The PCA EMG activity commenced 24.6 ± 2.2 milliseconds (p < .0001) before phrenic nerve discharge. The results are in accord with findings of earlier studies that show that PCA muscle activity commences prior to inspiratory airflow and diaphragmatic muscle activity. The data suggest that PCA and diaphragm motoneurons share common or similar medullary pre-motoneurons. The earlier onset of PCA muscle activity may indicate a role for medullary pre-inspiratory neurons in initiating PCA activity.

Glutamate Neurotransmission Is Not Required for, But May Modulate, Hypoxic Sensitivity of Pre-Bötzinger Complex In Vivo

2005 ◽  
Vol 93 (3) ◽  
pp. 1278-1284 ◽  
Author(s):  
Irene C. Solomon
Keyword(s):  
Phrenic Nerve ◽  
Excitatory Amino Acid ◽  
Glutamate Release ◽  
Receptor Activation ◽  
Motor Output ◽  
Induced Response ◽  
Homocysteic Acid ◽  
Bötzinger Complex ◽  
Nerve Discharge

Focal hypoxia in the pre-Bötzinger complex (pre-BötC) in vivo elicits excitation of inspiratory motor output by modifying the patterning and timing of phrenic bursts. Hypoxia, however, has been reported to enhance glutamate release in some regions of the brain, including the medullary ventral respiratory column; thus the pre-BötC–mediated hypoxic respiratory excitation may result from, or be influenced by, hypoxia-induced activation of ionotropic glutamate [i.e., excitatory amino acid (EAA)] receptors. To test this possibility, the effects of focal pre-BötC hypoxia [induced by sodium cyanide (NaCN)] were examined before and after blockade of ionotropic EAA receptors [using kynurenic acid (KYN)] in this region in chloralose-anesthetized, vagotomized, mechanically ventilated cats. Before blockade of ionotropic EAA receptors, unilateral microinjection of NaCN (1 mM; 10–20 nl) into the pre-BötC produced either phasic or tonic excitation of phrenic nerve discharge. Unilateral microinjection of KYN (50–100 mM; 40 nl) decreased the amplitude and frequency of basal phrenic nerve discharge; however, subsequent microinjection of NaCN, but not dl-homocysteic acid (DLH, a glutamate analog), still produced excitation of phrenic motor output. Under these conditions, the NaCN-induced excitation included frequency modulation (FM) of phasic phrenic bursts, and in many cases, augmented and/or fractionated phrenic bursts. These findings show that the hypoxia-sensing function of the in vivo pre-BötC, which produces excitation of phrenic nerve discharge, is not dependent on activation of ionotropic glutamate receptors, but ionotropic glutamate receptor activation may modify the expression of the focal hypoxia-induced response. Thus these findings provide additional support to the concept of intrinsic hypoxic sensitivity of the pre-BötC.

Pre-Bötzinger Complex Functions as a Central Hypoxia Chemosensor for Respiration In Vivo

2000 ◽  
Vol 83 (5) ◽  
pp. 2854-2868 ◽  
Author(s):  
Irene C. Solomon ◽  
Norman H. Edelman ◽  
Judith A. Neubauer
Keyword(s):  
Short Duration ◽  
Phrenic Nerve ◽  
Excitatory Amino Acid ◽  
Respiratory Rhythm ◽  
High Amplitude ◽  
Unique Region ◽  
Homocysteic Acid ◽  
Bötzinger Complex ◽  
Nerve Discharge

Recently, we identified a region located in the pre-Bötzinger complex (pre-BötC; the proposed locus of respiratory rhythm generation) in which activation of ionotropic excitatory amino acid receptors usingdl-homocysteic acid (DLH) elicits a variety of excitatory responses in the phrenic neurogram, ranging from tonic firing to a rapid series of high-amplitude, rapid rate of rise, short-duration inspiratory bursts that are indistinguishable from gasps produced by severe systemic hypoxia. Therefore we hypothesized that this unique region is chemosensitive to hypoxia. To test this hypothesis, we examined the response to unilateral microinjection of sodium cyanide (NaCN) into the pre-BötC in chloralose- or chloralose/urethan-anesthetized vagotomized, paralyzed, mechanically ventilated cats. In all experiments, sites in the pre-BötC were functionally identified using DLH (10 mM, 21 nl) as we have previously described. All sites were histologically confirmed to be in the pre-BötC after completion of the experiment. Unilateral microinjection of NaCN (1 mM, 21 nl) into the pre-BötC produced excitation of phrenic nerve discharge in 49 of the 81 sites examined. This augmentation of inspiratory output exhibited one of the following changes in cycle timing and/or pattern: 1) a series of high-amplitude, short-duration bursts in the phrenic neurogram (a discharge similar to a gasp), 2) a tonic excitation of phrenic neurogram output, 3) augmented bursts in the phrenic neurogram (i.e., eupneic breath ending with a gasplike burst), or 4) an increase in frequency of phrenic bursts accompanied by small increases or decreases in the amplitude of integrated phrenic nerve discharge. Our findings identify a locus in the brain stem in which focal hypoxia augments respiratory output. We propose that the respiratory rhythm generator in the pre-BötC has intrinsic hypoxic chemosensitivity that may play a role in hypoxia-induced gasping.

Protective role of epithelium in the guinea pig airway

1989 ◽  
Vol 66 (4) ◽  
pp. 1547-1552 ◽  
Author(s):  
M. Munakata ◽  
I. Huang ◽  
W. Mitzner ◽  
H. Menkes
Keyword(s):  
Guinea Pig ◽  
Protective Role ◽  
Airway Epithelial ◽  
Serosal Side ◽  
Epithelial Surface ◽  
Airway Responses ◽  
Airway Tone ◽  
Stimulation Of

We developed an in vitro system to assess the role of the epithelium in regulating airway tone using the intact guinea pig trachea (J. Appl. Physiol. 64: 466–471, 1988). This method allows us to study the response of the airway when its inner epithelial surface or its outer serosal surface is stimulated independently. Using this system we evaluated how the presence of intact epithelium can affect pharmacological responsiveness. We first examined responses of tracheae with intact epithelium to histamine, acetylcholine, and hypertonic KCl when stimulated from the epithelial or serosal side. We then examined the effect of epithelial denudation on the responses to these agonists. With an intact epithelium, stimulation of the inner epithelial side always caused significantly smaller changes in diameter than stimulation of the outer serosal side. After mechanical denudation of the epithelium, these differences were almost completely abolished. In the absence of intact epithelium, the trachea was 35-fold more sensitive to histamine and 115-fold more sensitive to acetylcholine when these agents were applied to the inner epithelial side. In addition, the presence of an intact epithelium almost completely inhibited any response to epithelial side challenge with hypertonic KCl. These results indicate that the airway epithelial layer has a potent protective role in airway responses to luminal side stimuli, leading us to speculate that changes in airway reactivity measured in various conditions including asthma may result in part from changes in epithelial function.

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