Central respiratory chemosensitivity: cellular and network mechanisms.
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Animals↗
Biomedical subjects
D Ballantyne
Publications and source records attributed to D Ballantyne.
Central chemosensitivity of respiration: a brief overview.
In this introductory article we make use of the work reviewed in detail by a number of contributors to this Special Issue (Respir. Physiol., 2001) to provide an outline of current approaches to identifying brainstem CO(2)/pH-chemosensitive neurones. The section headings which we have adopted are intended to reflect particular issues rather than experimental techniques, though some of these issues arise out of the choice of preparation and the advantages and limitations which follow from such a choice. We have also considered whether, in spite of the diversity in the kinds of neurones usually considered to be chemosensitive, there are any indications for shared or uniform features. Again, this is based on the material published together in this volume. Finally, and more speculatively, we suggest that the dendritic organization of chemosensitive neurones may play an important role in chemoreception, not simply as a means of sampling the stimulus but also as a way of compartmentalizing the effects of pH in relation to other aspects of a neurone's activity.
Animals↗
Synchronized rhythms in chemosensitive neurons of the locus coeruleus in the absence of chemical synaptic transmission.
The activity of locus coeruleus (LC) neurons was examined in the en bloc isolated brainstem-spinal cord of the neonatal rat using paired whole cell or whole cell plus extracellular recording. In artificial cerebrospinal fluid (ACSF) LC neurons were synchronized by their respiratory innervation and in some neurons showing tonic or burst patterns of discharge these patterns of discharge could also be synchronized. Replacing ACSF with low Ca(2+)-high Mg(2+) generated synchronized rhythmic bursts which remained synchronized at high CO(2) (up to 20%). This rhythm was suppressed by TTX. Substitution of Ba(2+) for Ca(2+) in ACSF generated a synchronized rhythm which was TTX-insensitive. The frequency of this rhythm increased by 31+/-16% on raising CO(2) concentration from 2 to 10%. We conclude that the capacity of chemosensitive LC neurons to generate a synchronized rhythm depends on their electrical coupling, but not on chemical synaptic transmission.
Animals↗
Mammalian brainstem chemosensitive neurones: linking them to respiration in vitro.
Neurones which are excited by CO2 or H+ are present in a number of brainstem structures in addition to the ventrolateral region of the medulla, the site at which the respiratory response to hypercapnia is traditionally believed to originate. In this review we examine recent work concerned with establishing the relationship between these chemosensitive neurones and respiration, the emphasis being placed on the use for this purpose of in vitro preparations of the mammalian brainstem.
Animals↗
Influences of variables for communicative targets after cochlear implantation.
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Adolescent↗
Residual hearing after cochlear implantation.
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Adult↗
Locus coeruleus neurones in vitro: pH-sensitive oscillations of membrane potential in an electrically coupled network.
The response to hypercapnic acidosis (2-8% CO2, bath pH 7.8-7.2) was examined in whole cell recordings from neonatal (P1 to P5) rat Locus coeruleus (LC) neurones in the in vitro brainstem-spinal cord preparation exposed to low Ca2+ (0.2 mM)-high Mg2+ (5 mM). This medium suppressed chemical synaptic transmission and resulted in a pattern of subthreshold oscillations of membrane potential and rhythmic burst discharge which was synchronized throughout the network. The oscillation was suppressed, and the discharge of individual neurones desynchronized, by the gap junction uncoupler, carbenoxolone, indicating that in low Ca2+-high Mg2+ LC neurones form an electrically coupled network. Switching from 2 to 8% CO2 decreased the oscillation amplitude and increased its frequency. The oscillation was suppressed by external Cd2+ and by TTX. but persisted during injection into the cell soma of QX-314. We conclude that in LC neurones acidosis increases the frequency of a Ca2+- and Na+-dependent dendritic oscillator which is synchronized by gap junction coupling throughout the network. This coupling is retained during acidosis.
Acidosis↗
'Small group' rehabilitation in adolescent cochlear implant users: learning experiences.
The reasons for which a group approach has been chosen for the small group rehabilitation of adolescent cochlear implant users are discussed. The most significant learning experiences after 18 months of treatment were the socialization of experience, the socialization of individual learning processes, the direct relationship between adolescents, practice discussion of topics of common interest, emphasizing of personal opinions and beliefs, experiencing collective 'products', the reinforcement of interpersonal relationships and the emphasizing of individual initiatives both at home and at school.
Adolescent↗
Respiration-modulated membrane potential and chemosensitivity of locus coeruleus neurones in the in vitro brainstem-spinal cord of the neonatal rat.
1. The activity of locus coeruleus (LC) neurones (n = 126) was examined in whole-cell (conventional and amphotericin B-perforated patch) recordings, and the relationship of this activity to the respiratory discharge recorded on the C4 or C5 phrenic nerve roots was determined at different CO2 concentrations (2 and 8 %; bath pH 7. 8 and 7.2) in the in vitro brainstem-spinal cord preparation of the neonatal rat (1-5 days old). 2. In most neurones (n = 105) ongoing activity was modulated at respiratory frequency. Typically, this consisted of a phase of depolarization and increased discharge frequency synchronous with the phrenic burst, followed by a phase of hyperpolarization and inhibition of discharge (n = 94 of 105). The incidence of respiratory modulation decreased from 91 % on P1 to 57 % on P5. 3. Bath application of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) or the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV; 100 microM) abolished both phases of respiratory modulation. The hyperpolarizing phase alone was abolished by the adrenoceptor antagonists idazoxan (5 microM) or phentolamine (0.8 microM). These results indicate that excitatory amino acid pathways are involved in the transmission of both the excitatory and inhibitory components and that the latter involves in addition an alpha2-adrenoceptor-mediated pathway. 4. Increasing the CO2 concentration from 2 to 8 % resulted in a shortening of expiratory duration and weakening or loss of respiratory-phased inhibition; this was accompanied by depolarization, increased discharge frequency and, in those neurones where they were initially present (60 %), an increase in the frequency of subthreshold membrane potential oscillations. The depolarizing response was retained in the presence of tetrodotoxin (TTX, 0.2-1.0 microM). 5. These results indicate that in this neonatal preparation LC neurones form part of the synaptically connected brainstem respiratory network, and that the LC constitutes a site of CO2- or pH-dependent chemoreception.
Acidosis↗
Chemosensitive medullary neurones in the brainstem--spinal cord preparation of the neonatal rat.
1. Using the isolated medulla and spinal cord of the neonatal rat, the response to CO2-induced changes in superfusate pH was examined in whole cell and perforated patch recordings from ventral medullary neurones which were identified by injection of Lucifer Yellow. The respiratory response to changing the CO2 concentration (from 2 to 8%) consisted of an increase in phrenic burst frequency, which could be accompanied by an increase, decrease or no change in burst amplitude. 2. Five classes of neurone - inspiratory, post-inspiratory, expiratory, respiration-modulated and ionic - were distinguished on the basis of their membrane potential and discharge patterns. Almost all (112 of 123) responded rapidly to 8% CO2 with a sustained change in membrane potential. Depolarizing responses (3-18 mV) occurred in inspiratory, respiration-modulated and 45% of tonic neurones. Hyperpolarizing responses (2-19 mV) occurred in expiratory and post-inspiratory neurones. The remaining tonic neurones were inhibited or showed no response. 3. In representatives of each class of neurone, membrane potential responses to 8% CO2 were retained when tested in the presence of tetrodotoxin (n = 7), low (0.2 mM) Ca(2+)-high (5 mM) Mg2+ (n = 23) or Cd2+ (0.2 mM) (n = 3)-containing superfusate, implying that they are mediated by intrinsic membrane or cellular mechanisms. 4. Neurones were distributed between 1200 microns rostral and 400 microns caudal to obex, and their cell bodies were located between 50 and 700 microns below the ventral surface (n = 104). Almost all responsive neurones (n = 78) showed dendritic projections to within 50 microns of the surface. 6. These experiments indicate that significant numbers of ventral medullary neurones, including respiratory neurones, are intrinsically chemosensitive. The consistency with which these neurones show surface dendritic projections suggests that this sensitivity may arise in part at this level.
Animals↗
A comparison of the effects of strength and aerobic exercise training on exercise capacity and lipids after coronary artery bypass surgery.
BACKGROUND: Coronary artery surgery improves symptoms and prognosis in patients with angina. Aerobic exercise rehabilitation improves exercise capacity and prognosis in cardiac patients. Strength exercise training has not been extensively studied. DESIGN: We studied the effects of 6 months aerobic and strength exercise training after coronary artery surgery in 81 men, mean age 57 years. RESULTS: Treadmill time(s) increased by 130.3 (95% confidence interval 46.4 to 214.2) in the aerobic group; by 83.1 (0.9 to 165.3) in the strength group, and by 34.3 (-1 to 69.6) in the control group (P = 0.04, control versus aerobic) after 3 months; and by 196.4 (112.2 to 280.7) in the aerobic group, by 122.7 (37.7 to 207.6) in the strength group and by 27 (-40.4 to 94.4) in the control group (P = 0.002, control versus aerobic, and P = 0.03 control versus strength) after 6 months. The level of fitness improved more in the strength-trained group, and there was a minor reduction in body weight and degree of fatness. There were no changes in lipoprotein levels. Aerobic exercise training causes early and sustained benefit in treadmill exercise capacity, while the effects of strength exercise training are later in onset. Exercise training alone did not influence lipid levels. CONCLUSION: Cardiac rehabilitation programmes should be comprehensive, including advice on diet and other risk factor modifications in addition to exercise sessions involving aerobic and strength training elements.
Aged↗
Relationship between ENT specialists and deaf community.
The relationship between the ENT specialist and the Deaf Community is discussed along with the relative role of the non-medical consultants who come into contact with this group of people. Suggestions are made to the clinician for a correct approach to deaf persons: acquisition of adeguate tools for communication and clear and understandable information. In this communication and clear and understandable information. In this context, the advent of Cochlear Implants and their impact on the Deaf Community are taken into consideration.
Cochlear Implants↗
Suppression of rhythmic discharges of medullary neurones in organotypic cultures of new-born rats by calcium antagonists.
The contribution of transmembrane calcium flux to the generation of periodic bioelectric activity in cultured organotypic medullary tissue of 6 day old rats was determined by adding calcium antagonists (CA) to the recording saline and by lowering the calcium concentration of this saline. Organic CA flunarizine and verapamil (50-100 mumol/l) reversibly suppressed rhythmic discharge and diminished the CO2 response of medullary neurones within 30-60 min. Inorganic CA cobalt and magnesium exerted the same effects within a few minutes. After lowering the calcium concentration rhythmic activity became unstable, but recovered on exposure to increased CO2 concentration, the excitatory effect of which was strongly reduced. These findings point to a significant role for transmembrane calcium flux and intracellular calcium concentration in sustaining both periodic activity and the CO2 response of medullary neurones.
Animals↗
Rhythm generation in organotypic medullary cultures of newborn rats.
Organotypic transverse medullary slices (obex level) from six-day-old rats, cultured for two to four weeks in chemically defined medium contained rhythmically discharging neurones which were activated by CO2 and H+. The mechanisms underlying this rhythmicity and the spread of excitation and synaptic transmission within this organotypic tissue were examined by modifying the composition of the external solution. Our findings showed that (1) Exposure to tetrodotoxin (0.2 microM) or to high magnesium (6 mM) and low calcium (0.2 mM) concentrations abolished periodic activity. (2) Neither the blockade of GABAergic potentials with bicuculline methiodide (200 microM) and/or hydroxysaclofen (200 microM) nor the blockade of glycinergic potentials with strychnine hydrochloride (100 microM) abolished rhythmicity. (3) While atropine sulphate (5 microM) was ineffective in modulating periodic discharges nicotine (100 microM) - like CO2-shortened the intervals between the periodic events; hexamethonium (50-100 microM) reduced both periodic and aperiodic activity. (4) Exposure to the NMDA antagonist 2-aminophosphonovaleric acid (50 microM) suppressed periodic events only transiently. In the presence of 2-aminophosphonovaleric acid rhythmicity recovered. However, the AMPA-antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10-50 microM), abolished periodic activity reversibly within less than 5 min. When 6-cyano-7-nitroquinoxaline-2,3-dione and nicotine were administered simultaneously periodic events persisted for up to 10 min. These findings indicate that synaptic excitatory drive is a prerequisite for the generation of rhythmic discharges of medullary neurones in this preparation. This drive may activate voltage-dependent channels or it may facilitate endogenous cellular mechanisms which initiate oscillations of intracellular calcium concentration. To test the latter possibility (5) calcium antagonists were added to the bath saline. The organic calcium antagonists verapamil and flunarizine (50-100 microM each) and the inorganic calcium antagonists cobalt (2 mM) and magnesium (6 mM) suppressed periodic activity and abolished or weakened the chemosensitivity towards CO2/acidosis. (6) Dantrolene (10 microM). an inhibitor of intracellular calcium release decreased the periodicity, while thapsigargin (2 microM) which blocks endoplasmic Ca(2+)-ATPase, transiently accelerated the occurrence of periodic events. (7) Oscillations of intracellular free calcium concentrations in Fura-2 AM-loaded cells were weakened or abolished by cobalt (2 mM). The results of (5)-(7) indicate that transmembrane calcium fluxes as well as intracellular Ca(2+)-release and -clearance mechanisms are a prerequisite for intracellular free calcium oscillations which may be important in the generation of rhythmic discharges in medullary neurones.
Animals↗
Experience with the Clarion device in children: surgical aspects, choice of strategy for stimulation and rehabilitation and preliminary results.
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Audiometry, Speech↗
Effect of exercise training on the total ischaemic burden: an assessment by 24 hour ambulatory electrocardiographic monitoring.
OBJECTIVE: To examine the effect of prolonged high intensity exercise training on total ischaemic burden in men with chronic stable angina pectoris. DESIGN: A randomised controlled trial based on 24 hour ambulatory electrocardiographic monitoring of patients on two occasions a year apart. SETTING: Cardiology department of a large general hospital. SUBJECTS: 40 men under 60 years of age with chronic stable angina pectoris and no previous myocardial infarction. RESULTS: After training the exercise group showed a 30% reduction in frequency of ST segment depression. There were significant reductions in painful episodes of ischaemia and those triggered by changes in heart rate. There was also a trend towards a reduction in silent ischaemia and episodes not triggered by changes in heart rate. The duration of ischaemic episodes was also reduced. No significant change in frequency or severity of dysrhythmia was shown. CONCLUSIONS: Exercise training reduces total ischaemic burden in patients with angina pectoris by reducing the frequency and duration of all types of ischaemic episode.
Adult↗
Influence of power and aerobic exercise training on haemostatic factors after coronary artery surgery.
OBJECTIVES: To determine the effects of aerobic and power exercise training on haemostatic factors after coronary artery surgery and to compare the effect of the two exercise programmes. DESIGN: A prospective randomised controlled study of six months aerobic and power exercise training in men after coronary artery surgery. SETTING: Exercise rehabilitation classes in a teaching hospital in Glasgow. PATIENTS: 55 men within 12 months of coronary artery surgery recruited from surgical centres and medical clinics and asked to participate in the study. INTERVENTIONS: Assessments, including a treadmill test, measurements of haemoglobin, platelet, fibrinogen, factor VIIc, and fibrinopeptide A concentrations, and packed cell volume, done at baseline, three months, and six months. Patients in the two exercise groups attended training sessions three times weekly for six months. Control patients had no formal exercise training but continued with their leisure time activities. MAIN OUTCOME MEASURES: Exercise performance on a treadmill, haematology, and haemostatic factor assays at baseline, three months, and six months. RESULTS: In the aerobic trained group exercise performance increased significantly over baseline at three months (interval change 146.7, 95% confidence interval (95% CI) 52.5 to 240.9 s, p = 0.003) and was maintained at six months (interval change 172.1, 95% CI 63.3 to 280.9 s, p = 0.002). In the power trained groups significant improvement in exercise performance was delayed until six months (interval change 99.9 s, 95% CI 20.3 to 170.5 s, p = 0.01). Exercise performance in the control did not change significantly. Haemoglobin, concentration, packed cell volume, and platelet counts did not change significantly at any time. Fibrinogen concentration was significantly lower in the aerobic group than the other two groups at three months (2.96 g/dl compared with 3.3 g/dl and 3.87 g/dl in the power and control groups, p = 0.01). The power group had a lower fibrinogen concentration than the control group (p = 0.04). The lower fibrinogen concentration in the aerobic group was maintained at six months. There was a gradual rise in factor VIIc concentrations in the aerobic and control groups compared with a small fall in the power group. Fibrinopeptide A concentrations showed no consistent changes. CONCLUSIONS: Aerobic exercise training after coronary artery surgery causes an early favourable change in treadmill performance and in fibrinogen concentrations, that is maintained with further training. Power exercise training causes delayed benefit in treadmill performance. It also causes a small fall in fibrinogen concentrations. These changes may be relevant in reducing cardiovascular morbidity from graft failure and occurrence of myocardial infarction after coronary artery surgery.
Adult↗