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Biomedical subjects

M S Dawid-Milner

Publications and source records attributed to M S Dawid-Milner.

At least 19 recordsLinked to original sources
PubMed2002

Laryngeal effects of stimulation of rostral and ventral pons in the anaesthetized rat.

In order to study the importance of two pontine regions modulating laryngeal resistance, electrical current or microinjections of glutamate (10-30 nl, 1-3 nmol) were made into the pontine parabrachial complex and the A5 region in spontaneously breathing anaesthetized rats. Two distinct patterns of laryngeal and respiratory responses were elicited. An increase of subglottal pressure was accompanied with an expiratory facilitatory response consisted of a decrease in both respiratory rate and phrenic nerve activity. A decrease of subglottal pressure was accompanied with an inspiratory facilitatory response consisted of an increase in both respiratory rate and phrenic nerve activity. The modification of laryngeal calibre occurred during both respiratory phases in most cases. The concomitant cardiovascular changes of these responses were also analyzed. Controls using guanethidine to block autonomic responses which might interact with respiratory control were also made. Histological analysis of stimulation sites showed a topographical organization of these responses: laryngeal constriction was evoked from Kölliker-Fuse, medial parabrachial nuclei and A5 region, whilst the laryngeal dilation was evoked from the lateral parabrachial nucleus.

Action Potentials↗
PubMed2001

Respiratory effects of stimulation of cell bodies of the A5 region in the anaesthetised rat.

To assess the importance of the pontine A5 region in modulating respiratory activity, electric current or microinjections of glutamate (10-30 nl, 1-3 nmol) were used to stimulate discrete zones within this region in the spontaneously breathing, anaesthetised rat. These stimuli evoked an expiratory facilitatory response, consisting of a decrease in respiratory rate (P < 0.01 electrical, P < 0.001 chemical) due to an increase of expiratory time (P < 0.01 in both cases) as measured from recordings of phrenic nerve activity. No changes were observed in inspiratory time. To avoid changes in PCO2, which could modulate the respiratory response, stimulation was also made during artificial ventilation. Under these conditions the expiratory facilitatory response elicited by glutamate was still present (P < 0.05), although its duration was reduced (P < 0.05), as was the magnitude of the phrenic burst (P < 0.05). At all the sites at which electrical stimulation and glutamate injection had evoked a respiratory response, electrical stimulation evoked a concomitant increase in both blood pressure and heart rate. Glutamate injection evoked a pressor response in 21 out of 30 animals. In eight animals the rise in blood pressure was followed by a fall in blood pressure and in one animal, a depressor response was observed. In all cases glutamate evoked an increase in heart rate. The expiratory facilitatory response was not evoked as a consequence of the increase of blood pressure since it was still present after the administration of guanethidine, which abolished the blood pressure changes. As glutamate is believed to excite perikarya rather than axons of passage these data indicate that expiratory facilitatory responses and the accompanying cardiovascular changes are the consequence of activating neurones located within the A5 region. The possible interactions between the A5 region and the medullary respiratory complex in eliciting these changes are discussed.

Anesthesia↗
PubMed1995

The pattern of excitatory inputs to the nucleus tractus solitarii evoked on stimulation in the hypothalamic defence area in the cat.

1. In anaesthetized, paralysed and artificially ventilated cats, recordings have been made in the nucleus tractus solitarii (NTS) to assess further the role of this nucleus in mediating the cardiorespiratory responses that are elicited on stimulation within the hypothalamic defence area (HDA). 2. The responses of NTS neurones to stimulation in the hypothalamus were assessed, as were their patterns of evoked response to electrical stimulation of the sinus (SN), aortic (AN), superior laryngeal (SLN) and vagus (VN) nerves. 3. Stimulation in the HDA affected the activity of 110 NTS neurones (85 studied in intracellular and 25 studied in extracellular recordings). The present study focused on those sixty-eight neurones that were excited by such stimulation (51 intracellular recordings and 17 extracellular recordings). 4. Of the sixty-eight neurones that were excited by HDA stimulation, seven revealed no changes in membrane potential or evoked discharge (2 neurones) but the stimulus facilitated the excitatory effects of stimulating either (or both) the SN and SLN. An additional group of neurones showed powerful excitatory responses to HDA stimulation (15 studied with extracellular and 35 with intracellular recording). Evoked EPSPs had onset latencies in the range of 1-30 ms. Of those thirty-five neurones displaying EPSPs, twenty-six were shown to receive convergent inputs on nerve stimulation. In nine neurones the early EPSP in response to HDA stimulation was followed by an IPSP. 5. In a further group of neurones HDA stimulation elicited a long-lasting IPSP, but this was not analysed further because its features have been described in detail in earlier studies from this laboratory. 6. The patterns of response of several neurones excited by stimulation in the HDA are consistent with them forming a group of NTS interneurones that mediate the hypothalamically evoked cardiovascular responses, including modulation of reflex function, which is a major feature of cardiorespiratory control. This possibility is discussed in the light of the present physiological observations and descriptions of an intrinsic NTS group of GABA-containing neurones that have been suggested to fulfil such a role.

Animals↗
PubMed1995

Hypothalamic modulation of laryngeal reflexes in the anaesthetized cat: role of the nucleus tractus solitarii.

1. This investigation was initiated because activation of laryngeal afferents, either by electrical stimulation of the superior laryngeal nerve (SLN) or by natural stimulation of receptors in the laryngeal mucosa, results in a cardiorespiratory response comprising bradycardia, hypotension and apnoea (phrenic nerve activity was suppressed). This pattern of response is qualitatively equivalent to the response that is evoked on activation of the arterial baroreceptors. 2. Preliminary studies indicated that the effects of activating the SLN were suppressed during stimulation in the hypothalamic defence area (HDA) at points that also blocked the effects of baroreceptor stimulation. 3. Recordings were taken from seventy-two neurones localized within the ipsilateral nucleus tractus solitarii (NTS) whose activity was modified by SLN stimulation. Sixty neurones responded with an EPSP on SLN stimulation; nine of these had an inspiratory firing pattern. Five neurones were seen to receive an IPSP on SLN stimulation. 4. Five respiratory SLN-activated neurones were unresponsive to stimulation of the other nerve inputs, whilst four received convergent EPSP inputs on sinus nerve (SN) stimulation. One cell of these four also received inputs from the aortic and the vagus nerves. Sixty-one non-respiratory SLN-activated neurones also received convergent inputs from the sinus nerve. Of these, fifty displayed an EPSP, four an IPSP and seven an EPSP-IPSP. Fifteen neurones also received inputs from the aortic nerve and seventeen from the vagus. 5. From the population of neurones affected by SLN stimulation, twenty-four of seventy were also influenced by HDA stimulation (3 were respiratory cells). Sixteen of these responses consisted of an EPSP (2 respiratory cells), five of an IPSP (1 respiratory cell) and three of an EPSP-IPSP. 6. In neurones receiving an IPSP on HDA stimulation, the SLN-evoked excitatory response was reduced throughout the period of HDA-evoked inhibition. These neurones were all shown to receive excitatory inputs from the arterial baroreceptors and laryngeal mechanoreceptors. 7. Additionally, in the thirty-seven neurones that were excited by SLN stimulation but received no direct synaptic input on HDA stimulation, a conditioning stimulus to the HDA evoked a block of SLN-evoked responses without an accompanying change in membrane potential. Several of these neurones were also affected by both baroreceptor and laryngeal mechanoreceptor stimulation. 8. These observations are discussed in the context of the role of the NTS in cardiorespiratory control. The potential importance of these interactions in respiratory distress are highlighted and the implications for the organization of central pathways for the control of autonomic and respiratory function are discussed.

Anesthesia↗
PubMed1995

Hypothalamic modulation of the arterial chemoreceptor reflex in the anaesthetized cat: role of the nucleus tractus solitarii.

1. There is evidence in the literature of a mutual facilitatory interaction between the arterial chemoreceptor reflex and the alerting stage of the defence reaction, particularly in relation to the patterning of cardiorespiratory activity. The present study has been designed to test the hypothesis that a portion of this interaction involves synaptic interactions within the nucleus tractus solitarii (NTS). 2. The study has involved an analysis of the effective interactions between the stimulation of the arterial chemoreceptors and the hypothalamic defence area (HDA) on the activity of NTS neurones recorded in anaesthetized, paralysed and artificially ventilated cats. 3. A group of eighteen NTS neurones was classified as chemosensitive, on the basis of displaying EPSPs on sinus nerve stimulation (SN) and their failure to show an excitatory response to baroreceptor stimulation. Thirteen of these neurones displayed pronounced excitatory responses to chemoreceptor stimulation. In sixteen of these neurones HDA stimulation elicited an EPSP; in four of these sixteen neurones this early EPSP was followed by an IPSP. In the remaining two (of 18) neurones HDA stimulation provoked no obvious synaptic response but facilitated the efficacy of both chemoreceptor inputs and SN stimulation. 4. Neurones shown to receive convergent inputs from the arterial chemoreceptors (and SN stimulation) and HDA, often displayed excitatory responses to stimulation of other peripheral inputs. Vagally evoked EPSPs were observed in nine neurones, SLN-evoked responses in seven neurones and aortic nerve-evoked EPSPs in three neurones. 5. The organization of these synaptic interactions is discussed and these data are used to explain the pattern of interaction between chemoreceptor, baroreceptor and HDA inputs within the NTS. Conclusions are drawn regarding the functional role of different classes of NTS neurone, based on the findings in this and the accompanying two papers.

Anesthesia↗
PubMed1994

Cardiovascular and respiratory effects of stimulation of cell bodies of the parabrachial nuclei in the anaesthetized rat.

1. In order to assess the importance of the parabrachial nuclei in modulating cardiorespiratory activity, electric current or microinjections of glutamate were used to stimulate discrete regions of the parabrachial nuclei in anaesthetized rats. 2. Stimulation of cell bodies in the medial region of the parabrachial nuclei and in the Kölliker-Fuse nuclei, caused an expiratory facilitatory response. This consisted mainly of a decrease in respiratory rate as measured by observing phrenic nerve activity. 3. Stimulation of cell bodies in the lateral region of the parabrachial nuclei caused an inspiratory facilitatory response. This consisted mainly of an increase in respiratory rate. 4. At the majority of sites (16 out of 20) where changes in respiratory rate were elicited by glutamate injection or electrical stimulation an increase in blood pressure was observed. The coexistence of increases in blood pressure and heart rate indicates the presence of inhibition of the heart rate component of the baroreflex and/or an increase in cardiac sympathetic drive. 5. The expiratory facilitatory response was not evoked reflexly by the rise in blood pressure since it was still present after administration of guanethidine, which abolished the rise in blood pressure. 6. The interactions between the parabrachial nuclei and the medullary respiratory complex in eliciting these changes are discussed.

Animals↗
PubMed1994

A potential role of central A1 adenosine receptors in the responses to hypothalamic stimulation in the anaesthetized cat.

In pentobarbitone anaesthetized and paralysed cats the effects of the A1 adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) have been observed on the pressor response to stimulation of the hypothalamic defence area (HDA) and on the effects of baroreceptor and chemoreceptor reflex activation on arterial blood pressure. The administration of DPCPX decreased the magnitude of the HDA pressor response and the chemoreceptor induced rise in blood pressure. The fall in blood pressure induced by baroreceptor activation was enhanced to a small yet significant extent. No changes were observed in the tachypnoea evoked by hypothalamic defence area (HDA) stimulation. These results suggest a possible role for central adenosine A1 receptors in mediating the cardiovascular changes evoked during HDA stimulation.

Adenosine↗
PubMed1994

Action of adenosine receptor antagonists on the cardiovascular response to defence area stimulation in the rat.

1. The action of adenosine in the mediation of the cardiovascular changes associated with the defence reaction has been investigated in the rat using two A1 receptor antagonists. 2. Cumulative doses of 1,3 dipropyl-cyclopentylxanthine (DPCPX) (0.3-3 mg kg-1) and ethanol (0.03-0.25 ml) and bolus doses of DPCPX (3 mg kg-1) and 8-sulphophenyltheophylline (8-SPT) (20 mg kg-1) were given into alpha-chloralose, paralysed and artificially ventilated rats. Recordings were made of arterial blood pressure and heart rate. 3. Ethanol, the vehicle for DPCPX, failed to modify the magnitude of the defence response; however, cumulative doses of DPCPX produced a dose-dependent decrease in the HDA (hypothalamic defence area)-evoked increase in arterial blood pressure, accompanied by a similar fall in the magnitude of the evoked heart rate response. 4. The evoked rise in arterial blood pressure was reduced significantly by intravenous injection of DPCPX (3 mg kg-1) but not 8-SPT (20 mg kg-1), a purely peripherally acting adenosine antagonist. 5. These results suggest that adenosine acting at A1 receptors located in the central nervous system, is involved in the HDA-evoked pressor response. Whilst the site of action of the A1 receptors is not known, possible locations are discussed.

Adenosine↗
PubMed1993

Hypothalamic-evoked effects in cat nucleus tractus solitarius facilitating chemoreceptor reflexes.

In anaesthetized cats intracellular recordings in the nucleus tractus solitarius (NTS) have been used to identify neurones receiving inputs from the carotid sinus nerve (SN), the aortic nerve and hypothalamic defence area (HDA). In forty-four neurones activated by SN stimulation HDA activation evoked an IPSP in fourteen (32%) and an EPSP in eight (11%). Those neurones receiving an HDA-evoked IPSP, and tested for reflex inputs, responded only to baroreceptor activation. Neurones receiving HDA-evoked EPSPs responded only to chemoreceptor activation. In three neurones unaffected by SN stimulation, short latency inputs from HDA were observed, suggesting direct monosynaptic inputs.

Action Potentials↗
PubMed1993

Activity of inspiratory neurones of the ambiguus complex during cough in the spontaneously breathing decerebrate cat.

In spontaneously breathing, decerebrate cats, extracellular recordings in the intermediate region of the ambiguus complex have been used to characterize the activity of inspiratory laryngeal motoneurones (ILMNs) during mechanical stimulation of tracheal irritant receptors. Laryngeal resistance was measured using an isolated larynx in situ. The effect of tracheal stimulation was analysed successfully in twenty-seven neurones. Eleven were ILMNs and sixteen inspiration-related neurones. Inspiration-related neurones increased their phasic discharge frequency during tracheal stimulation while ILMNs fired tonically, during both the inspiratory and the expiratory efforts of the cough. The tonic discharge of ILMNs coincided with a decrease of laryngeal resistance.

Afferent Pathways↗
PubMed1993

Effects of bronchoconstriction on the cough reflex in the cat.

The present study was aimed to analyse the influence of bronchoconstriction (Carbachol, 10 micrograms/kg, i.v.) on the cough response to mechanical stimulation of the tracheal mucosa. Experiments were performed in anaesthetised and spontaneously breathing cats, using the isolated glottis technique. Airflow, pleural pressure, subglottic pressure, blood pressure and total lung resistance were recorded. During bronchoconstriction, the cough response was inhibited significantly as shown by the decrease in the number of cough efforts (p < 0.001), in maximum flow during inspiratory (p < 0.001) and expiratory (p < 0.001) movements and in the change of the expiratory (p < 0.01) and inspiratory (p < 0.01) pleural pressures. The mechanical stimulation of the tracheal mucosa evoked always a prolonged decrease of the larynx resistance, including those cases with inhibition of the cough. This study shows that the activation of some type of receptors during bronchoconstriction can modify the cough response to mechanical stimulation of the tracheal mucosa. On the other hand, the widening of the glottis, an associated component of the cough response, can be obtained separately, suggesting that the laryngeal response is centrally integrated via different mechanisms.

Airway Resistance↗
PubMed1992

Acute alcoholic intoxication and naloxone. Effects on visual evoked potential.

Experimental assays analyzing visual evoked potential (VEP) changes during an acute alcoholic intoxication were carried out in two groups of cats: One with continuous ethanol (0.06 g/kg.min) i.v. perfusion. Another one with a naloxone (400 micrograms/kg) i.v. injection 10 min before ethylic perfusion. Naloxone potentiates alcohol effects on VEP parameters, and on the appearance of isoelectric postpotential and flat VEP.

Acute Disease↗
PubMed1989

Neuropeptide Y-like immunoreactivity in the brain stem respiratory nuclei of the cat.

The distribution of fibres and cell bodies containing neuropeptide Y-like immunoreactivity in respiratory nuclei of the brain stem was studied using an indirect immunoperoxidase technique. In order to visualize immunoreactive perikarya, intraventricular or intratissue injections of colchicine were carried out. The richest cluster of immunoreactive perikarya was localized in the Bötzinger complex, whereas in the nuclei ambiguus, retroambiguus, parabrachialis medialis and Kölliker-Fuse area, a moderate density of cell bodies was observed. The ventrolateral subnucleus of the nucleus tractus solitarii had the lowest number of immunoreactive neurons. Neuropeptide Y-like immunoreactive fibres were abundant in the Kölliker-Fuse area, and scarce in the nuclei ambiguus, parabrachialis medialis and Kölliker-Fuse area. A moderate network of immunoreactive fibres was observed in the nuclei retroambiguus and the ventrolateral subnucleus of the nucleus tractus solitarii. The presence of neuropeptide Y-like immunoreactive areas suggests a role for this peptide in the control of respiratory mechanisms. Alternatively such a cluster of cell bodies and fibre networks might be also related with neighbouring cardiovascular control areas.

Animals↗
PubMed1989

Effect of naloxone on acute ethylic intoxication. An EEG study.

EEG recording has been used to evaluate in cats the effect of naloxone on acute ethylic intoxication (AEI). Naloxone was administered both before and during the course of AEI. Results of the experiment showed that administration of naloxone before the AEI potentiates the toxic effect of alcohol. However, the administration of naloxone in a continuous way along the course of AEI significantly diminished the toxic effect of alcohol.

Animals↗
PubMed1989

Electroencephalographic study of naloxone effects in the recovery of an acute alcoholic intoxication.

Experimental assays analysing EEG changes during the recovery of an acute alcoholic intoxication were carried out in three groups of cats: 1) Recovery of acute alcoholic intoxication produced by continuous intravenous perfusion of ethanol, 0.06 g/kg/min, during 20 minutes. 2) Recovery of acute alcoholic intoxication by injecting naloxone (400 micrograms/kg), just after finishing alcohol perfusion. 3) Recovery of acute alcoholic intoxication by injecting naloxone (400 micrograms/kg), 15 min after finishing perfusion. Naloxone administered after an acute alcoholic intoxication worsens the recovery of EEG parameters; 1-2 (p less than 0.05), 1-3 (p less than 0.05).

Alcoholic Intoxication↗
PubMed1989

[Changes in laryngeal resistance and bronchial tonus].

The modifications of larynx resistance changing bronchial tone were studied in cats. Changes on bronchial tone were evoked by intravenous administration of Carbachol (10 micrograms/kg) as bronchoconstrictor, and by Fenoterol (10 micrograms/kg) and Isoprenaline (0.1 mg/kg) as bronchodilators. The effects of Carbachol administration after these drugs were also studied. Larynx resistance was measured by the subglottic pressure value using the in situ isolated glottis technique. Subglottic pressure increases after Carbachol administration (p less than 0.001) and decreases after Fenoterol (p less than 0.02) and Isoprenaline (p less than 0.01). When Carbachol was administered after the bronchodilators subglottic pressure values were similar to those observed in control situations. A high positive correlation between changes of subglottic pressure and total lung resistance (p less than 0.01) was also observed. These results could suggest that glottis contraction was reflexively modified by bronchial tone.

Airway Resistance↗
PubMed1989

[Effects of tobacco smoke applied on various levels of the respiratory tract].

The respiratory and cardiovascular reflex responses of tobacco smoke inhaled through an isolated larynx and directly into the lungs were studied in cats. The inhalation of tobacco smoke directly into the lungs showed the following: tachypnea (p less than 0.01), an increase in inspiratory and expiratory pleural pressure (p less than 0.01, p less than 0.001) with an increase in total lung resistance (p less than 0.01), a decrease in inspiratory and expiratory subglottic pressure (p less than 0.001, p less than 0.02) and an increase in mean arterial pressure (p less than 0.001) with a non significant slight increase of cardiac rate. The inhalation through an isolated larynx showed: bradypnea (p less than 0.01), a non significative decrease in inspiratory and expiratory pleural pressure with no changes in total lung resistance, and an increase in expiratory subglottic pressure (p less than 0.01) with no changes in inspiratory pressure accompanied by several glottic closures. No changes in arterial pressure and cardiac rate were observed. This study shows the existence of two respiratory reflex responses induced by tobacco smoke depending on the respiratory airway level application.

Animals↗