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Biomedical subjects

J Mitra

Publications and source records attributed to J Mitra.

At least 55 records · Page 3Linked to original sources
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↗
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↗
PubMed1986

Medullary effects of nicotine and GABA on tracheal smooth muscle tone.

Airway tone can be modulated centrally by the brain as well as by peripheral receptors. In part these changes in airway caliber seem to be secondary to changes in respiratory activity. Since structures near the ventrolateral medullary surface (VMS) can produce profound effects on respiration, it seems reasonable to believe that they might also be capable of modifying tracheal tone. In this study we examined the effects of two agents with respect to their action on tracheal tone: nicotine, a respiratory stimulant when applied to the VMS, and gamma aminobutyric acid (GABA), a respiratory depressant when similarly administered. In chloralose anesthetized, paralyzed, artificially ventilated cats, tracheal tone was assessed by measuring pressure changes in a rostral bypassed segment of the trachea, while phrenic nerve activity was examined simultaneously. Nicotine administered on the intermediate area of the VMS both before and after carotid sinus denervation increased phrenic activity and induced constriction of the rostral tracheal segment. The response to nicotine could be blocked by application of a nicotine antagonist, hexamethonium, or prior local administration of lidocaine to the VMS. Activation of GABAergic receptors by application of GABA on the intermediate area of the VMS markedly reduced respiratory activity and nearly abolished the increased tracheal tone produced by inhalation of 7% CO2 in O2. The effects of GABA were eliminated by the prior administration to the VMS of bicuculline, a GABA receptor antagonist. These results indicate that structures located on the ventral surface of the medulla which affect breathing may also play a significant role in the regulation of airway smooth muscle tone.

Administration, Topical↗
PubMed1986

Comparison of the effects of hypercapnia on phrenic and hypoglossal activity in anesthetized decerebrate and decorticate animals.

To examine the effects of suprapontine structures on the activity of hypoglossal and phrenic nerves, 13 chloralose anesthetized, paralyzed (gallamine triethiodide) and artificially ventilated cats were studied. In all animals vagi and carotid sinus nerves were cut bilaterally. All animals were first hyperventilated to apnea and then made progressively hypercapnic by rebreathing under hyperoxic conditions. Following midcollicular decerebration, the peak phasic activity of the hypoglossal nerve was significantly depressed and the PCO2 at which apnea occurred (apneic point) increased. However, following high decerebration or decortication the activity of the hypoglossal nerve was increased at higher CO2 levels and there was no change in apneic point. By contrast, peak phrenic nerve activity was not altered by any of the above surgical procedures. Neither systemic blood pressure nor respiratory frequency were significantly altered by these procedures. The results indicate that suprapontine structures can appreciably modify hypoglossal activity.

Anesthesia, General↗
PubMed1986

Effect of focal cooling of central chemosensitive areas on cerebral ischemic response.

The ventrolateral medullary surface (VMS) has been shown to have chemosensitive areas that can alter blood pressure and respiration. It has also been shown that lesions near the VMS can affect the intensity of the cerebral ischemic response (CIR). To determine which regions of the central chemosensitive areas of the ventral medullary surface contribute to the pressor response caused by cerebral ischemia, we used focal cooling of the caudal Loescheke's (CL), intermediate Schlaefke's (IS), and rostral Mitchell's (RM) areas of VMS during ischemia of the brain. Experiments were performed on 17 pentobarbital sodium-anesthetized, paralyzed, and artificially ventilated cats after denervation of the vagi and sinoaortic nerves. Bilateral occlusion of the external carotid and vertebral arteries resulted in a significant increase of arterial pressure (from 129 +/- 4 to 174 +/- 8 mmHg, P less than 0.01) and an increase in splanchnic sympathetic activity. However, heart rate and cervical sympathetic activities were not appreciably affected by cerebral ischemia. Bilateral cooling of the IS area to as low as 10 degrees C led to a decrease or disappearance of phrenic activity but failed to affect the magnitude of the pressor response. Also cooling of the CL and RM areas and application of Gelfoam pledgets soaked in lidocaine (4%) to these areas did not affect the CIR. However, covering the whole VMS with 0.2 ml of 4% lidocaine or cold cerebrospinal fluid (10 degrees C) abolished the ischemic reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1986

Influence of ventrolateral surface of medulla on reflex tracheal constriction.

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.

Administration, Topical↗
PubMed1986

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

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.

Animals↗
PubMed1986

Analysis of postinspiratory activity of phrenic motoneurons with chemical and vagal reflexes.

We examined the effects of chemical and reflex drives on the postinspiratory inspiratory activity (PIIA) of phrenic motoneurons using a single-fiber technique. Action potentials from "single" fibers were recorded from the C5 phrenic root together with contralateral mass phrenic activity (also from C5) in anesthetized, paralyzed, and artificially ventilated cats with intact vagus and carotid sinus nerves. Nerve fibers were classified as "early" or "late" based on their onset of discharge in relation to mass phrenic activity during hyperoxic ventilation. Only the early fibers displayed PIIA but not the late fibers, even when their activity began earlier in inspiration with increased chemical drives. Isocapnic hypoxia increased, whereas hyperoxic hypercapnia shortened the duration of PIIA. Pulmonary stretch and "irritant" receptors inhibited PIIA. Hypercapnia and stimulation of peripheral chemoreceptors by lobeline excited both early and late units to the same extent, but hypoxic ventilation had a less marked excitatory effect on late fiber activity. Irritant receptor activation increased the activity of early more than late fibers. Hyperoxic hyperventilation eliminated late phrenic fiber activity, whereas early fibers became tonically active. Bilateral vagotomy abolished this sustained discharge in eight of nine early units, suggesting the importance of vagal afferents in producing tonic firing during hyperventilation. These results suggest that early and late phrenic fibers have different responses to chemical stimuli and to vagally mediated reflexes; late units do not discharge in postinspiratory period, whereas early fibers do; the PIIA is not affected in the same way by various chemical and vagal inputs; and early units that exhibit PIIA display tonic activity with hyperoxic hypocapnia.

Action Potentials↗
PubMed1986

Responses of hypoglossal and phrenic nerves to decreased respiratory drive in cats.

Agents which depress respiration, such as alcohol, seem to increase the occurrence of obstructive apneas during sleep. It has been proposed that upper airway obstruction can result from an imbalance in the activity (or forces) produced by the upper airway muscles versus the chest wall muscles so that upper airway passages might be blocked when a disproportionate decrease in upper airway muscle activity occurs. This study examines the hypothesis that depression of respiration affects the activity of the hypoglossal nerve (the motor nerve to the tongue) more than the activity of the phrenic nerve (the motor nerve to the diaphragm). In addition, we examined the role of the putative central chemoreceptor area on the ventrolateral medullary surface (VMS) in maintaining phrenic and hypoglossal discharge. In chloralose-anesthetized, artificially ventilated, paralyzed cats, three methods of reducing respiratory drive were studied: hyperoxic hypocapnia (produced by mechanical hyperventilation), the application to the intermediate area of the ventral medullary surface of the respiratory depressant GABA and its agonist muscimol, and cooling the same area of the VMS (using a water-cooled thermode). All these interventions decreased hypoglossal nerve activity more than phrenic nerve activity (range of p values: p less than 0.001 to p less than 0.01). Moreover, the reduction in hypoglossal activity was greater with GABA and muscimol than with the other two maneuvers; this was statistically significant for both GABA versus VMS cooling (p less than 0.02) and muscimol versus VMS cooling (p less than 0.01). These results show that respiratory depression can differentially affect hypoglossal and phrenic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The effects of hypercapnia and cooling the ventral medullary surface on capsaicin induced respiratory reflexes.

The effect of right atrial (RA) injection of 3 micrograms/kg capsaicin on phrenic, hypoglossal and recurrent laryngeal activities was studied in chloralose anesthetized, paralyzed and artificially ventilated cats. Within 2 sec following capsaicin injection, the phrenic and hypoglossal activities completely disappeared (apnea), while the recurrent laryngeal activity markedly increased. Similar responses were also obtained with RA injection of phenyldiguinide (PDG), suggesting that the respiratory responses of both drugs are essentially similar. Sino-aortic denervation did not affect the capsaicin induced respiratory responses. Bilateral vagotomy abolished the responses, suggesting that vagal sensory receptors are responsible for the reflex effects. Hyperoxic hypercapnia (3 and 7% CO2 in O2) reduced the apneic duration of phrenic and hypoglossal nerves. The magnitude of the recurrent laryngeal excitation was decreased during CO2 breathing. Graded focal cooling of the intermediate area (Is area) of the ventral medullary surface (to inhibit central chemoreceptor activity) significantly prolonged capsaicin induced apneic duration of hypoglossal nerves more than the phrenic. The recurrent laryngeal responses, however, were unaffected by cooling of the ventral medullary surface. The results show that capsaicin and PDG, presumably by stimulating C fibers, affect cranial nerves as well as the phrenic. The reflex responses to C fiber stimulation seem to be altered by intervention which stimulate (hypercapnia) or depress (Is cooling) 'central chemoreceptors.'

Animals↗
PubMed1985

Influence of central chemoreceptor afferent inputs on respiratory muscle activity.

Respiratory activity can be substantially affected by perturbations confined to the superficial areas of the ventrolateral surface of the medulla, the putative site of central chemoreceptors. In this study we compared the effect of thermal and pharmacological interventions that are known to alter respiration on the electrical activity of the rib cage muscles, diaphragm, and abdominal muscles. With cooling of the intermediate areas to 20 degrees C, tidal volume decreased 50%. The electrical activity of the diaphragm decreased less than the other muscles (diaphragm less than inspiratory intercostal less than expiratory intercostal). Abdominal muscle activity was depressed as much as expiratory intercostal activity but reappeared with further cooling to 10 degrees C if cooling was prolonged and the vagi were intact. gamma-Aminobutyric acid (GABA) and its agonist muscimol, like cooling, reduced expiratory and inspiratory intercostal activity more than diaphragm activity. Nicotine, a respiratory stimulant, applied to the intermediate areas increased inspiratory intercostal activity more than the diaphragm. The results suggest that under the conditions of the experiments the rib cage musculature, and probably the abdominal muscles as well, are more responsive than the diaphragm to depression or excitation of chemosensitive elements in the superficial regions of the medulla.

Animals↗
PubMed1984

Comparison of the responses of the diaphragm and upper airway muscles to central stimulation of the sciatic nerve.

Electrical stimulation of the central end of the sciatic nerve was used to assess the effect of increased somatic sensory input on respiratory muscle electrical activity in anesthetized, spontaneously breathing dogs. Graded electrical stimulation of the sciatic nerve was associated with progressively greater activity of the upper airway dilating muscles (alae nasi, genioglossus, and posterior cricoarytenoid) as well as the diaphragm. Breathing frequency also increased because of a reduction in inspiratory and expiratory time. After cessation of stimulation of the sciatic nerve, increased activity of all the muscles studied persisted and only gradually returned to control levels. The responses to sciatic nerve stimulation were independent of the CO2 concentration of the inspired gas mixture. At any level of chemical drive electrical stimulation caused greater increases in the electrical activity of upper airway dilating muscles than that of diaphragm. Based on these results, it is concluded that stimulation of sciatic nerve activates upper airway muscles as well as the diaphragm, and the upper airway muscle activity is augmented to a greater degree than diaphragm activity. It seems possible that somatosensory afferent input produces unequal effects on different respiratory motoneurons.

Animals↗
PubMed1984

Action of nicotine on the respiratory activity of the diaphragm and genioglossus muscles and the nerves that innervate them.

Nicotine is known to alter respiration by stimulating peripheral chemoreceptors and receptors within the brain. In this study the sites of action and the effects of nicotine on hypoglossal nerve activity were compared to its effects on phrenic activity in paralyzed, vagotomized and chloralose-anesthetized cats. Since anesthesia is known to affect respiratory responses, we also compared the effects of intravenous nicotine given to conscious unsedated cats on genioglossus and diaphragm electrical activity. In eight conscious animals intravenous doses of nicotine ranging between 10 ng and 200 micrograms increased genioglossus activity significantly more than diaphragm activity. Studies in 26 anesthetized animals included injection of nicotine, intravenously, in the lateral ventricles, and application of nicotine to the ventrolateral surface of the medulla (the putative site of the central chemoreceptors) before and after section of the carotid sinus nerves. With all these interventions, changes in hypoglossal nerve activity were significantly greater than changes in phrenic nerve activity. The responses to nicotine could be blocked by application of hexamethonium to the ventrolateral medullary surface or by cooling the same area. The results indicate that: nicotine increases hypoglossal nerve activity by both its peripheral and central effects; nicotine has differential effects on different respiratory muscles and nerves; and the central action of nicotine may be mediated largely through receptors located near the ventral medullary surface.

Anesthesia↗
PubMed1984

Responses of upper airway, intercostal and diaphragm muscle activity to stimulation of oesophageal afferents in dogs.

The effects of oesophageal distension on respiratory patterns and the moving average electromyogram (e.m.g.) activity of three upper airway muscles--the alae nasi, the genioglossus, and the posterior cricoarytenoid--and four chest wall muscles--the costal and crural diaphragm and the inspiratory and expiratory intercostals--were examined in ten anaesthetized, tracheostomized, spontaneously breathing dogs. Distension was produced by inflations of a balloon placed in the middle part of the thoracic oesophagus with volumes of air ranging from 50 to 200 ml. Oesophageal distension increased respiratory frequency, mainly due to a significant shortening of the expiratory time. Activity of both the costal and crural parts of the diaphragm was inhibited with oesophageal distension, whereas that of the inspiratory intercostal muscles increased, tending to maintain a near-normal tidal volume and end-tidal CO2. Phasic inspiratory activity of all three upper airway muscles increased in response to oesophageal distension, as did the activity of the expiratory intercostal muscles. The changes in the breathing pattern and the electrical activity of all muscles in response to oesophageal distension were immediate, occurring during the first breath after the balloon was inflated. The responses were graded, so that increases in the volume of the oesophageal balloon progressively increased the activity of the upper airway and intercostal muscles, and decreased diaphragm activity. Bilateral vagotomy abolished the effects of oesophageal distension on upper airway and chest wall muscle activity, suggesting that vagal afferents constitute the major pathway for the reflex.

Animals↗
PubMed1984

Hypoglossal and phrenic responses to cholinergic agents applied to ventral medullary surface.

Application of cholinergic agents on the ventrolateral surface of the medulla in areas in which the "central chemoreceptors" are believed to be located stimulates breathing. It is also known that cranial nerves, such as the hypoglossal, have respiratory modulated activity (greater in inspiration than expiration) that responds to many of the same stimuli which affect breathing. In the present study we compared effects of cholinergic agents (acetylcholine, carbachol, methacholine, eserine) directly applied to chemoreceptive areas on the ventral medullary surface on phrenic and hypoglossal nerve activity. Studies were performed in paralyzed, anesthetized, and artificially ventilated cats after vagotomy. All cholinergic agents increased hypoglossal activity significantly more than phrenic activity in animals ventilated with O2 or 7% CO2 in O2 whether or not the carotid sinus nerves were intact. Atropine applied topically to the same medullary area blocked the respiratory effects of locally administered acetylcholine. The results suggest that cholinergic agents applied centrally can increase both phrenic and hypoglossal activity. Moreover the effects of the drugs are relatively greater on XII nerve activity than on phrenic discharge, suggesting that the drive from medullary cholinergic structures is distributed with unequal weight to different respiratory motoneurons.

Acetylcholine↗
PubMed1984

Responses to chemical stimulation of upper airway muscles diaphragm in awake cats.

The steady-state and transient effects of hyperoxic hypercapnia on the electromyographic activities of the genioglossus (GG), posterior cricoarytenoid (PCA), and diaphragm (D) were studied in conscious unsedated cats with chronically implanted electrodes. Hypercapnia (inhalation of 3.4 and 7.4% CO2 in O2) increased the phasic electrical activity occurring during inspiration in all three muscles and also increased tonic activity of the GG. The GG responded to steady-state CO2 inhalation alinearly and with larger increases in activity than the PCA and D. Phasic GG activity was present in only 4 of 10 cats breathing 100% O2, whereas phasic PCA and D activity could be observed in all animals studied. When gas mixtures containing CO2 were given, the GG reached its new steady-state level more slowly than the D or PCA, and when CO2 was rapidly removed from the inspired gas mixture, the GG attained its steady state sooner than either the PCA or D. These results suggest that in awake unsedated animals, chemical stimuli do not affect either transient or steady-state responses of the GG in the same way as the D. These differences seem to be explained mainly by different threshold characteristics of hypoglossal and phrenic neurons but also in part by dissimilarities in their steady-state responses.

Animals↗
PubMed1984

Effects of dopamine, isoproterenol, and lobeline on cranial and phrenic motoneurons.

Recent studies have suggested that the upper airway muscles receive a substantial portion of their excitatory input from the peripheral chemoreceptors. We examined the responses of the phrenic, hypoglossal, and recurrent laryngeal nerves to agents that are known to modify carotid body activity. Dopamine, an inhibitor, and isoproterenol and lobeline, two stimulators of carotid body activity, were administered into the lingual arteries of 14 anesthetized, paralyzed cats artificially ventilated with 100% O2. Dopamine decreased the activity of all three nerves (P less than 0.001) but inhibited the hypoglossal nerve more than the phrenic and recurrent laryngeal nerves (P less than 0.001). Isoproterenol and lobeline increased the activity of all three nerves (P less than 0.001) but stimulated the hypoglossal nerve more than the phrenic and recurrent laryngeal nerves (P less than 0.001). These relatively greater effects of all three agents on the hypoglossal nerve compared with the phrenic and the recurrent laryngeal nerves persisted under both hypoxic and hypercapnic conditions. After midcervical vagotomy, the responses of the hypoglossal to all three drugs remained larger than those of the phrenic nerve. After combined vagotomy and carotid sinus nerve section, the stimulatory effects of lobeline and the inhibitory effects of dopamine were no longer apparent. We conclude that it is possible to preferentially alter respiratory-related activity of the hypoglossal nerve compared with that of the phrenic nerve using agents that modify peripheral chemoreceptor activity.

Animals↗