Excitatory Phenomena Research Articles

Influence of the glutamate antagonist riluzole on intracortical inhibitory and excitatory phenomena

Influence of the glutamate antagonist riluzole on intracortical inhibitory and excitatory phenomena

Increased neuronal excitability during depolarization‐induced suppression of inhibition in rat hippocampus.

1. Depolarization-induced suppression of inhibition (DSI) is a form of plasticity of gamma-amino-butyric acid (GABAA)-mediated (henceforth 'GABAergic') responses in the CNS. We made whole-cell recordings from CA1 pyramidal neurons to investigate the effects of DSI on excitatory synaptic transmission in the hippocampal slice preparation. 2. Significant enhancement of the voltage-clamped excitatory postsynaptic current (EPSC) occurs during DSI of the temporally overlapping inhibitory postsynaptic current. With high levels of calcium chelators in the pipette solution, or bath application of bicuculline, EPSC enhancement is blocked, suggesting that it results from DSI and that the DSI process selectively affects GABAergic, but not glutamatergic, transmission. 3. The probability of synaptically evoked action potential firing is increased during DSI under current clamp. DSI could influence other excitatory phenomena as well.

Propofol infusion technique for outpatient general anesthesia

Purpose: The purpose was to evaluate the suitability of a continuous propofol infusion in combination with alfentanil for outpatient general anesthesia in an oral and maxillofacial surgery practice. Materials and Methods: Twenty-seven ASA 1 patients were selected to undergo oral and maxillofacial surgery outpatient procedures of short duration. Induction of anesthesia was accomplished with 1 mg/kg intravenous (IV) propofol and 10 μg/kg IV alfentanil. Local anesthesia was administered. General anesthesia was maintained with a continuous infusion of 150 μg/kg/min of propofol. Various physical and psychomotor responses were recorded during induction, maintenance, emergence, and recovery. Results: Anesthesia was successfully induced in all patients with single, slowly titrated, bolus doses of 1 mg/kg of propofol and 10 μg/kg of alfentanil. Induction of general anesthesia occurred in less than 1 minute in all cases and no excitatory phenomena, tremor, or hypertonus were observed. Maintenance of anesthesia was adequately accomplished and cardiovascular parameters remained within acceptable limits throughout the procedure. The average length of surgery was 22 minutes. Movement to surgical stimulus was minimal and easily managed with additional local anesthetic and/or a 10-mg bolus of propofol. Time to eye opening was approximately 5 minutes from the discontinuation of the propofol infusion. No emergence phenomena were observed. All patients were ready for discharge with baseline psychomotor activity within 30 minutes following the end of the procedure. The average total dose of propofol was 350 mg and the average dose of alfentanil was 750 μg. Conclusion: This anesthetic technique has numerous advantages with minimal side effects, and should be considered for routine use for outpatient general anesthesia in oral and maxillofacial surgery.

Effects of acute sleep deprivation on control of the diaphragm during REM sleep in cats.

Recently, investigators demonstrated that acute sleep deprivation in healthy subjects results in significant periodic decrements in ventilation during recovery rapid-eye-movement (REM) sleep. The neural bases of such phenomena are unknown. The decrements in ventilation coincide with REM sleep-associated phasic activities, such as bursts of eye movements. The purpose of this study was to determine the effects of acute sleep deprivation on control of diaphragm activity during recovery REM sleep. In chronically implanted, naturally sleeping, unrestrained cats, we recorded the electroencephalogram, electrooculogram, pontogeniculooccipital waves, neck and diaphragmatic electromyograms, and the computed moving average of the diaphragm. Acute sleep deprivation resulted in an increase in REM sleep-associated phasic alterations in diaphragmatic control during recovery REM sleep. There was an increase in the percentage of bursts during recovery REM sleep with reduced inspiratory drive. Acute sleep deprivation resulted in a substantial increase in the number of brief pauses (fractionations) in diaphragmatic activity during recovery REM sleep. Respiratory timing was also affected by sleep deprivation, with a reduced expiratory time resulting in an increased duty cycle ratio. There was a significant increase in the percentage of bursts with decremented peak amplitude of the moving average of the diaphragm, a measure that correlates with tidal volume. Despite significant increases in respiratory-related phasic alterations, there were no parallel increases in excitatory phenomena, i.e., eye movements or pontogeniculooccipital waves. These results imply that respiratory control mechanisms in REM sleep are sensitive to the effects of prior sleep deprivation.

Methohexital dissolved in lipid emulsion for intravenous induction of anesthesia in infants and children.

The induction dose of thiopental and propofol has been shown previously to vary during childhood. The methohexital dose needed for satisfactory induction of anesthesia in 50% of patients (ED50) was determined in 75 infants and children, 1 month to 16 yr of age. An intravenous bolus of methohexital, dissolved in a lipid emulsion to decrease pain on injection, was given over 10 s. After 30 s the anesthesia mask was applied. The patient was considered to be asleep if there were no gross movements when the head was placed in the sniffing position and the anesthesia mask applied, and no response to verbal command (tested in children more than 4 yr of age) during the next 30 s while the patient breathed O2. ED50 (+/- SE) was 2.6 +/- 0.2 mg/kg in infants 1-6 months of age, 1.9 +/- 0.1 mg/kg in infants 7-11 months of age, 1.4 +/- 0.1 mg/kg in children 1-3 yr of age, 1.1 +/- 0.1 mg/kg in children 4-7 yr of age, and 1.3 +/- 0.1 mg/kg in children 8-16 yr of age. ED50 in each of the two groups of infants was significantly greater than ED50 in each of the three other groups (P less than 0.05). Pain or discomfort on injection was observed in 1 infant and 3 children (5%). Eight patients (11%) had apnea longer than 15 s, and excitatory phenomena occurred in 9 (12%). It is concluded that the dose of methohexital needed for induction of anesthesia varies with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Decrease of β-Endorphin in the Brain of Rats Following Nitrous Oxide Withdrawal

beta-Endorphin levels in the whole rat brain were not changed during acute (25 min) or chronic (48 h) exposure of rats to N2O. However, a significant decrease of beta-endorphin was found in the whole brain, brain stem and subcortex during the withdrawal from chronic exposure to N2O. It has been suggested that decrease of beta-endorphin levels during N2O withdrawal could be ascribed to unspecific stress accompanying drug withdrawal. Decrease of central beta-endorphin during N2O withdrawal might have a significant modulatory effect on transmitter balance, neuronal excitability and corresponding withdrawal behaviour. Furthermore, the decrease of beta-endorphin levels in the whole brain during N2O withdrawal might contribute to the postanaesthesia N2O-excitatory syndrome in humans. This might explain the known therapeutic effect of the opioid drug, meperidine on the excitatory N2O withdrawal phenomena during recovery from N2O anaesthesia in man.

The Electroencephalographs Effects of Desflurane in Humans

The electroencephalographic (EEG) effects of a new inhaled anesthetic are of interest because of the potential of such agents to produce excitatory (convulsant) activity and because of the potential usefulness of the EEG as an indicator of anesthetic depth and cerebral activity. Accordingly, we examined the EEG in 12 healthy, young male volunteers during desflurane anesthesia. Each subject had a baseline recording and then steady-state exposure to 6, 9, and 12% (0.83, 1.24, and 1.66 MAC) desflurane in O2 alone, and to 3, 6, and 9% desflurane in O2 with 60% N2O. The sequence of doses and the presence of N2O were randomized. We used mechanical ventilation to maintain normocapnia at each dose level. We also tested the effects of hypercapnia secondary to spontaneous ventilation. Additionally, at 1.24 MAC, subjects' lungs were hyperventilated to a PCO2 of 25.8 +/- 0.7 mmHg and exposed to rhythmic, loud clapping to attempt to provoke excitatory phenomena. Finally, after at least 6 h exposure to desflurane, we repeated measurements at 0.83 and 1.66 MAC to assess possible tolerance. Four channels of EEG were monitored visually, and at each dose, a quantitative EEG analysis was performed. Desflurane produced EEG changes comparable to those observed with equipotent levels of isoflurane. No epileptiform activity was seen. Desflurane significantly suppressed EEG activity; prominent burst suppression was seen at 1.24 MAC and higher. Substitution of N2O for 0.42 MAC desflurane reduced the degree of EEG suppression relative to the equipotent administration of desflurane and O2. Quantitative EEG measures for the early doses and for the later, repeated exposures did not differ.

Excitatory phenomena following the use of propofol in dogs

Over a two month period, 148 dogs presented for surgery had general anaesthesia induced and sometimes maintained with propofol. Excitatory phenomena were recorded on 12 occasions. Signs included muscle twitching, opisthotonus and limb hyperextension (nine cases), and panting with associated activity of the brachiocephalicus muscle and tongue retraction (three cases). The records for a similar two month period were examined for data and observations relating to thiopentone. During this period anaesthesia was induced with thiopentone in 71 dogs and no excitatory phenomena were recorded.

Excitatory phenomena of artificial membrane impregnated with surfactant

Excitatory phenomena of artificial membrane impregnated with surfactant

Discharge patterns of laryngeal motoneurones in the cat: an intracellular study

In decerebrate cats, stable intracellular recordings were made from 37 laryngeal motoneurones, the membrane potentials of which varied in relation to respiration. These motoneurones were identified as laryngeal since all were antidromically activated by stimulation of the recurrent laryngeal nerve, but in two, the antidromic activity could only be elicited by vagal stimulation (vagotomized cats). The cell bodies were all located within the nucleus ambiguus. Sixteen cells were depolarized during the phrenic burst and were classified as inspiratory laryngeal motoneurones (ILM). Thet repolarized at end-inspiration and received two successive waves of postsynaptic inhibition during expiration: an early, strong one and a late (end-expiratory), weaker one. The decay of the first wave was related to the duration of postinspiratory phrenic activity. Twenty-one cells depolarized abruptly in early expiration followed by a more-or-less gradual repolarization. They were classified as expiratory laryngeal motoneurones (ELM). All ELM were strongly inhibited during inspiration. Some of them received weak inhibition during end expiratory phase. The rapid and large depolarization observed during early expiration (and consequent maximal discharge frequency) can be explained by two summating mechanisms: a postinhibitory rebound resulting from the removal of inhibition during inspiration, and an excitatory phenomenon of unknown origin. The amplitude of this excitatory phenomenon was largest in cats with the most residual (early expiratory) phrenic activity. To explain the hyperpolarizations occurring in ELM during late expiratory and inspiratory phases and those occurring in ILM during early expiration, we hypothesize that reciprocal inhibition exists between networks controlling ILM and ELM activities or between these motoneurones themselves. The cause of the relationship between residual phrenic nerve activity and the events in early expiration in both ILM (hyperpolarization) and ELM (depolarization) remains to be elucidated. Our observations are consistent with the braking effect on expiratory flow in postinspiration caused by the activation of the adductor muscles driven by the expiratory laryngeal motoneurones, and the release of the abductor muscles driven by the inspiratory laryngeal motoneurones.

Correlation between the distribution of 3H-labelled enkephalin in rat brain and the anatomical regions involved in enkephalin-induced seizures

The correlation between the distribution of the intraventricularly (i.v.t.) administered δ agonist [ 3H]( D-ala 2, D-leu 5)-enkephalin ([ 3H]DADL) and the anatomical regions involved in enkephalin-induced seizures has been studied in rat by using an autoradiographic method and recording of the electromyogram (EMG) and the electroencephalogram (EEG). The results indicate that within 10 min, the radioactivity of the intraventricularly administered drug reached all parts of the ventricular system, including the central canal of the spinal cord. However, within 2.5 min after the intraventricular administration of [ 3H]DADL, which corresponds to the onset of DADL-induced seizures, the substance appeared mainly in the left lateral ventricle and occasionally in the third ventricle. During the first 2.5 min the substance penetrated regularly into the surrounding periventricular tissue of the striatum, septum and hippocampus to a depth of about 100 μm. The most intensive and long-lasting epileptic discharges, exceeding 30 min were observed in the hippocampus, in contrast to the mild and short-lasting electrophysiological responses of the septum and corpus striatum. The experiments suggest that the short onset of enkephalin-induced excitatory phenomena is due to the rapid distribution and penetration of the substance in the surrounding periventricular tissue. According to these data, it is proposed that activation of δ opiate receptors, localized within the first 100 μm of the periventricular tissue, mainly in the hippocampus, is essential for the triggering of endorphin-induced seizure activity.

MAO-B inhibitor deprenyl and beta-phenylethylamine potentiate [D-ALA2]-Met-enkephalinamide-induced seizures.

The relationship between deprenyl (MAO-B inhibitor), beta-phenylethylamine (PEA, MAO-B substrate) and [D-Ala2]-Met-enkephalinamide (DALA)-induced seizure was studied in the urethane-anaesthetized rats. A combined electromyographic (EMG) and electrocorticographic (ECoG) method was used. PEA (20-100 micrograms ivt) or DALA (10 micrograms ivt) induced myoclonic contractions (MC) in the submandibular muscle and epileptiform pattern with spike activity in the ECoG. Administration of subconvulsant doses of PEA (5-10 micrograms ivt 0.5-1 min before DALA) significantly increased DALA-induced seizure activity. Similarly, blockade of MAO-B with deprenyl (3-48 mg/kg ip) also enhanced DALA-induced epileptiform pattern. It is evident from this study that MAO-B system significantly modulates the excitatory phenomena induced by DALA. These findings of interactions between MAO-B system and enkephalinergic one, might be of relevance in the clinical situations such as psychosis, stress, a use of tricyclic antidepressants and all other cases, where the alteration of MAO-B system is a part of disease or induced during drug therapy.

Ionic events responsible for the cardiac resting and action potential

The cardiac action potential is distinguished from other excitatory phenomena by a prominent plateau and by the latent pacemaking capability of cardiac muscle. A review of experimental data suggests that ionic fluxes through gated membrane channels are the primary determinants of the shape of the cardiac action potential. The rapid depolarization phase of the action potential is mediated in part by an ionic channel that resembles the sodium ion (Na+) channel of nerve. A slower channel capable of carrying both calcium ion (Ca2+) and Na+ currents (Isi) also contributes to the upstroke of the action potential. The Ca2+ current through this channel is partly responsible for maintaining the plateau phase of the action potential. Moreover, because this slower channel activates at more positive potentials in partly depolarized myocardium or in specialized conduction tissue such as the sinoatrial and atrioventricular nodes. Two distinct transport systems appear to be the principal regulators of potassium ion (K+) in myocardium. An inwardly rectifying, voltage-dependent K+ channel apparently maintains all K+ conductance at rest and at all potentials negative to --20 mV. A second channel, which is both voltage- and time-dependent, evidently mediates K+ flux during the plateau phase of the action potential. This K+ current activates at potentials positive to --20 mV. The role of coupled transport mechanisms is now well established. The low intracellular concentrations of Na+ and Ca2+ prevailing in the myocardium are maintained by an electrogenic Na+ pump and a Na+-Ca2+ counter-transport system. Current data on carrier-mediated transport systems are insufficient to delineate the role of such mechanisms in the control of cardiac action potential. Further studies are required to provide details of the voltage, temporal and ionic dependence of gated channels, as well as of ionic counter-transport carriers, so that a quantitative reconstruction of cardiac action potential may be attempted.

EFFECT OF PREANAESTHETIC MEDICATION ON ETOMIDATE

The effects of diazepam and pethidine, when given as preanaesthetic medication, on the induction of anaesthesia and the postanaesthetic sequelae following etomidate were studied in women undergoing minor gynaecological procedures. Pain on injection was present in all the groups. However, the frequency was significantly less with the polyethylene glycol and propylene glycol formulations of the drug compared with the aqueous solution. A fast injection and pethidine premedication decreased the frequency also. The high frequency of excitatory phenomena in unpremedicated patients was decreased significantly by premedication with diazepam and pethidine, especially the latter. Respiratory and cardiovascular effects of the drug were not major problems. The frequency of emetic sequelae was high. Recovery was rapid even in the groups receiving sedative premedication.

EVALUATION OF THREE PREPARATIONS OF ETOMIDATE

Three formulations of etomidate were evaluated in unpremedicated patients undergoing minor gynaecological procedures. There was a high frequency of pain on injection (up to 50%) and excitatory phenomena (up to 95%) with all formulations. The frequency of excitatory phenomena was significantly greater than that after methohexitone. Recovery was rapid, but emetic sequelae were frequent and significantly more marked than after methohexitone.

EFFECT OF DOSE AND PREMEDICATION ON INDUCTION COMPLICATIONS WITH ETOMIDATE

The induction characteristics of etomidate, a new i.v. hypnotic agent, were studied in 400 patients. Two hundred were premedicated with atropine and anaesthesia was induced with 0.2, 0.25, 0.3 or 0.35 mg/kg of etomidate. The remainder received one of four standard premedications and anaesthesia was induced with etomidate 0.3 mg/kg. Involuntary muscle movements occurred in more than 60% of patients receiving atropine alone. The frequency was reduced in the second group, but remained unacceptable in over 8% of patients. The incidence of other excitatory phenomena, such as cough and hiccup, was 10% approximately. Cardiovascular changes were minimal and no serious allergic phenomena were observed. Nausea and vomiting occurred after surgery in up to 30% of patients and was unrelated to the dose of etomidate or to premedication. Pain on injection occurred in up to 80% of patients when the drug was injected into small peripheral veins and occurred in more than 7% when using more normal veins.

ANAESTHESIA FOR CARDIOVERSION: A comparison of diazepam, thiopentone and propanidid

Three groups of 50 patients were anaesthetized with diazepam 0.32 mg/kg or thiopentone 3.7 mg/kg or propanidid 4.6 mg/kg for elective carfioversion. Propanidid caused more hypotension than diazepam or thiopentone. Apnoea was most frequent following thipentone and excitatory side-effects were most prominent following propanidid; the electric countershock worsened the excitatory phenomena. The success rate of conversion was higher in the diazepam group than in the other groups, but the difference was not statistically significant. Diazepam failed to produce amnesia in about 33% of the patients. Thiopentone is suitable and pleasant for cardioversion. Diazepam is recommended in poor-risk patients and in emergency situations.

Postsynaptic phenomena in optic tectum neurons following optic nerve stimulation in fish

In the field potential evoked in optic tectum by electrical stimulation of the optic nerve, the first postsynaptic deflection (wave 4) is shown to represent (a) a graded excitatory phenomenon which gives rise to (b) a spike followed by refractory period. The second postsynaptic deflection (wave 5) probably also represents 2 such phenomena. Both the graded and spike potentials, sustained by vertically elongated neurons, originate in the tectal strata where the bulk of retino-tectal afferents terminate, i.e., the stratum fibrosum et griseum superficiale. The positive-negative (or purely positive) configuration of unitary spikes recorded at deep tectal strata, presumably from the neuronal perisomatic region, suggests that the monosynaptic excitatory phenomena are sustained by the fusiform and large pyriform neurons, whose somata are deeply located. Also neurons whose somata lie in superficial tectal strata are excited monosynaptically, and they most likely also contribute to the field potential. Among these are large neurons which always fire in association with wave 5. Inhibitory phenomena, evidenced by depression of neuronal excitability, set in some 10 msec after the stimulus and lasted for 40–200 msec. For the first 40 msec or so, a slight facilitatory state can be shown to overlap with this depression.

Effect of pentylenetetrazol on the leech Retzius cell

Pentylenetetrazol, 1–10 m m, caused reversible hyperpolarization, cessation of spontaneous firing and fall in input resistance of the Retzius cells of leech segmental ganglia. Transient depolarization and increased firing also occurred in the early portion of the response in some cells. The hyperpolarization and input resistance changes occurred in the presence of 20-m m magnesium sulfate, but the early excitatory phenomena never did. Substitution of propionate for chloride in the bathing fluid reduced the hyperpolarization and input resistance change in proportion to the reduction of chloride. In the absence of all external chloride, and with a potassium chloride rather than a potassium acetate electrode in the cell, the drug caused depolarization and increased firing. The typical drug response occurred in the absence of external potassium and the presence of ouabain, 0.1 m m. These data demonstrate that the principal effect of pentylenetetrazol on this particular neuron is a direct, selective, and reversible increase in the chloride permeability of some substantial portion of its membrane. Increased electrogenic ion pumping does not appear to be a significant factor in the response. It is noted that the overall effect of increased chloride permeability in a population of neurons is theoretically quite complex, owing to the fact that the chloride equilibrium potential is negative to the firing level in some cells and positive to it in others.

Effect of LSD-25 (lysergic acid — diethyl amide) on the Energetic Metabolism of the Brain of Rats

Authors investigated the effect of LSD-25, of chlorpromazine, and of a combination of both on three parts of the brain of white rats (I: cortex and white substance extending to the subcortex; II: subcortical ganglia and medulla oblongata; III: cerebellum) upon the level of total reducing substance, glycogen, lactic, and pyruvic acid, ATP, and anorganic P. Twenty minutes after injecting 2ɣ per 100 g of LSD-25, subcutaneously, in I the glycogen level increased significantly, that of total reducing substance significantly decreasing. In II: concentration of both metabolites showed significant decrease. In III: that of pyruvic acid decreased nearly significantly. The so-called ‘Whole Brain Value’ computed from the average of total reducing substance, and pyruvic acid contents as found in the three brain parts showed a significant decrease. Twenty minutes after injecting, subcutaneously, 0.30 mg per 100 g of chlorpromazine the content of total reducing substance increased significantly in II and III, the glycogen level increased nearly significantly in II where lactic acid showed a significant decrease while pyruvic acid concentration decreased significantly in all three parts. The ‘Whole Brain Value’ of the latter showed a significant decrease, total reducing substance and glycogen content increased nearly significantly. Twenty minutes after injecting, subcutaneously, 2ɣ per 100 g of LSD-25 and 0.30 mg per 100 g of chlorpromazine the ATP level in III decreased significantly, that of anorganic P showing a significant increase. The ‘Whole Brain Value’ of pyruvic acid decreased significantly, that of anorganic P increased, also significantly. Authors consider the metabolic change caused by LSD-25 to be of a dissimilatory type, that upon chlorpromazine of assimilatory type relating them to the excitatory phenomena of the central nervous system as caused by LSD-25, and the inhibitive phenomena as caused by chlorpromazine. They found a partial antagonism between the effect of both drugs upon the carbohydrate metabolism of the brain tissue. On the grounds of literary data they discuss to what degree their results might be utilized for explaining the biochemical basic processes of LSD psychosis.