Dependence of explicit and implicit memory on hypnotic state in trauma patients.
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BACKGROUND: It is still unclear whether memory of intraoperative events results entirely from moments of inadequate anesthesia. The current study was designed to determine whether the probability of memory declines with increasing depth of the hypnotic state. METHOD: A list of words was played via headphones during surgery to patients who had suffered acute trauma. Several commonly used indicators of anesthetic effect, including the bispectral index, were recorded during word presentation. First, these indicators served as predictors of the memory performance in a postoperative word stem completion test. Second, general memory performance observed in the first part was separated into explicit and implicit memory using the process dissociation procedure, and then two models of memory were compared: One model assumed that the probability of explicit and implicit memory decreases with increasing depth of hypnotic state (individual differences model), whereas the other assumed equal memory performance for all patients regardless of their level of hypnotic state. RESULTS: General memory performance declined with decreasing bispectral index values. None of the other indicators of hypnotic state were related to general memory performance. Memory was still significant at bispectral index levels between 60 and 40. A comparison of the two models of memory resulted in a better fit of the individual differences model, thus providing evidence of a dependence of explicit and implicit memory on the hypnotic state. Quantification of explicit and implicit memory revealed a significant implicit but no reliable explicit memory performance. CONCLUSIONS: This study clearly indicates that memory is related to the depth of hypnosis. The observed memory performance should be interpreted in terms of implicit memory. Auditory information processing occurred at bispectral index levels between 60 and 40. (+info)
Changes in core temperature compartment size on induction of general anaesthesia.
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A two-compartment model of temperature distribution estimates the core compartment to occupy 66% of body mass at rest, while the peripheral compartment comprises the remainder. General anaesthesia impairs thermoregulation by central and peripheral actions. Peripheral vasodilatation accelerates heat transfer from the core to peripheral compartment causing the core compartment to cool and expand in size. Core hypothermia may be a significant cause of postoperative morbidity. This undocumented change in the size of the core compartment on induction of anaesthesia can be calculated. Core size increased from the established value of 66% before induction of general anaesthesia to 71.2 (SD 6)% of body mass, 20 min after induction of anaesthesia (P = 0.0001). On induction of general anaesthesia, the core compartment cools and expands while the peripheral compartment warms and contracts by a corresponding amount. Measurement of the magnitude of changes in core:periphery heat distribution on induction of anaesthesia contribute to a clearer understanding of the pathophysiology of perioperative hypothermia. (+info)
Structural consequences of anesthetic and nonimmobilizer interaction with gramicidin A channels.
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Although interactions of general anesthetics with soluble proteins have been studied, the specific interactions with membrane bound-proteins that characterize general anesthesia are largely unknown. The structural modulations of anesthetic interactions with synaptic ion channels have not been elucidated. Using gramicidin A as a simplified model for transmembrane ion channels, we have recently demonstrated that a pair of structurally similar volatile anesthetic and nonimmobilizer, 1-chloro-1,2,2-trifluorocyclobutane (F3) and 1,2-dichlorohexafluorocyclobutane (F6), respectively, have distinctly different effects on the channel function. Using high-resolution NMR structural analysis, we show here that neither F3 nor F6 at pharmacologically relevant concentrations can significantly affect the secondary structure of the gramicidin A channel. Although both the anesthetic F3 and the nonimmobilizer F6 can perturb residues at the middle section of the channel deep inside the hydrophobic region in the sodium dodecyl sulfate micelles, only F3, but not F6, can significantly alter the chemical shifts of the tryptophan indole N-H protons near the channel entrances. The results are consistent with the notion that anesthetics cause functional change of the channel by interacting with the amphipathic domains at the peptide-lipid-water interface. (+info)
Multisecond oscillations in firing rate in the basal ganglia: robust modulation by dopamine receptor activation and anesthesia.
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Multisecond oscillations in firing rate in the basal ganglia: robust modulation by dopamine receptor activation and anesthesia. Studies of CNS electrophysiology have suggested an important role for oscillatory neuronal activity in sensory perception, sensorimotor integration, and movement timing. In extracellular single-unit recording studies in awake, immobilized rats, we have found that many tonically active neurons in the entopeduncular nucleus (n = 15), globus pallidus (n = 31), and substantia nigra pars reticulata (n = 31) have slow oscillations in firing rate in the seconds-to-minutes range. Basal oscillation amplitude ranged up to +/-50% of the mean firing rate. Spectral analysis was performed on spike trains to determine whether these multisecond oscillations were significantly periodic. Significant activity in power spectra (in the 2- to 60-s range of periods) from basal spike trains was found for 56% of neurons in these three nuclei. Spectral peaks corresponded to oscillations with mean periods of approximately 30 s in each nucleus. Multisecond baseline oscillations were also found in 21% of substantia nigra dopaminergic neurons. The dopamine agonist apomorphine (0.32 mg/kg iv, n = 10-15) profoundly affected multisecond oscillations, increasing oscillatory frequency (means of spectral peak periods were reduced to approximately 15 s) and increasing the regularity of the oscillations. Apomorphine effects on oscillations in firing rate were more consistent from unit to unit than were its effects on mean firing rates in the entopeduncular nucleus and substantia nigra. Apomorphine modulation of multisecond periodic oscillations was reversed by either D1 or D2 antagonists and was mimicked by the combination of selective D1 (SKF 81297) and D2 (quinpirole) agonists. Seventeen percent of neurons had additional baseline periodic activity in a faster range (0.4-2.0 s) related to ventilation. Multisecond periodicities were rarely found in neurons in anesthetized rats (n = 29), suggesting that this phenomenon is sensitive to overall reductions in central activity. The data demonstrate significant structure in basal ganglia neuron spiking activity at unexpectedly long time scales, as well as a novel effect of dopamine on firing pattern in this slow temporal domain. The modulation of multisecond periodicities in firing rate by dopaminergic agonists suggests the involvement of these patterns in behaviors and cognitive processes that are affected by dopamine. Periodic firing rate oscillations in basal ganglia output nuclei should strongly affect the firing patterns of target neurons and are likely involved in coordinating neural activity responsible for motor sequences. Modulation of slow, periodic oscillations in firing rate may be an important mechanism by which dopamine influences motor and cognitive processes in normal and dysfunctional states. (+info)
A single amino acid confers barbiturate sensitivity upon the GABA rho 1 receptor.
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Many structurally diverse general anaesthetics enhance inhibitory neurotransmission in the central nervous system by interacting with the GABAA receptor. By contrast, GABA receptors composed of the rho 1 subunit are anaesthetic-insensitive. Here, we demonstrate that both delta-hexachlorocyclohexane (delta-HCH; 1-100 microM), a positive allosteric modulator of the GABAA receptor, and the anaesthetic pentobarbitone (10-600 microM) have no effect on GABA-evoked currents mediated by wild-type rho 1 recombinant receptors (expressed in Xenopus laevis oocytes). By contrast, these agents produce up to a 10 fold enhancement of GABA responses transduced by a rho 1 receptor in which a transmembrane located isoleucine residue is replaced by serine. However, not all general anaesthetics were similarly influenced by this mutation, because propofol and 5 beta-pregnan-3 alpha-ol-20-one (5 beta 3 alpha) remained ineffective. These data are discussed in relation to the specificity of general anaesthetic action. (+info)
Distinctly different interactions of anesthetic and nonimmobilizer with transmembrane channel peptides.
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Although it plays no clinical role in general anesthesia, gramicidin A, a transmembrane channel peptide, provides an excellent model for studying the specific interaction between volatile anesthetics and membrane proteins at the molecular level. We show here that a pair of structurally similar volatile anesthetic and nonimmobilizer (nonanesthetic), 1-chloro-1,2,2-trifluorocyclobutane (F3) and 1, 2-dichlorohexafluorocyclobutane (F6), respectively, interacts differently with the transmembrane peptide. With 400 microM gramicidin A in a vesicle suspension of 60 mM phosphatidylcholine-phosphatidylglycerol (PC/PG), the intermolecular cross-relaxation rate constants between (19)F of F3 and (1)H in the chemical shift regions for the indole and backbone amide protons were 0.0106 +/- 0.0007 (n = 12) and 0.0105 +/- 0.0014 (n = 8) s(-1), respectively. No cross-relaxation was measurable between (19)F of F6 and protons in these regions. Sodium transport study showed that with 75 microM gramicidin A in a vesicle suspension of 66 mM PC/PG, F3 increased the (23)Na apparent efflux rate constant from 149.7 +/- 7.2 of control (n = 3) to 191.7 +/- 12.2 s(-1) (n = 3), and the apparent influx rate constant from 182.1 +/- 15.4 to 222.8 +/- 21.7 s(-1) (n = 3). In contrast, F6 had no effects on either influx or efflux rate. It is concluded that the ability of general anesthetics to interact with amphipathic residues near the peptide-lipid-water interface and the inability of nonimmobilizer to do the same may represent some characteristics of anesthetic-protein interaction that are of importance to general anesthesia. (+info)
General anaesthetic actions on ligand-gated ion channels.
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The molecular mechanisms of general anaesthetics have remained largely obscure since their introduction into clinical practice just over 150 years ago. This review describes the actions of general anaesthetics on mammalian neurotransmitter-gated ion channels. As a result of research during the last several decades, ligand-gated ion channels have emerged as promising molecular targets for the central nervous system effects of general anaesthetics. The last 10 years have witnessed an explosion of studies of anaesthetic modulation of recombinant ligand-gated ion channels, including recent studies which utilize chimeric and mutated receptors to identify regions of ligand-gated ion channels important for the actions of general anaesthetics. Exciting future directions include structural biology and gene-targeting approaches to further the understanding of general anaesthetic molecular mechanisms. (+info)
Comparison of bispectral index, 95% spectral edge frequency and approximate entropy of the EEG, with changes in heart rate variability during induction of general anaesthesia.
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We have compared bispectral index (BIS), 95% spectral edge frequency (SEF) and approximate entropy (ApEn) in 37 patients during induction and recovery from a short general anaesthetic. Heart rate variability (HRV) was also compared during induction only. These indices were noted at the start of induction, when a syringe held between the thumb and fingertips was dropped, at insertion of a laryngeal mask or tracheal tube (tube insertion), at incision, at the end of surgery, on return of the gag reflex and when the patient could follow a verbal command. When indices at the start of induction were compared with those at tube insertion, all four decreased significantly. BIS decreased from a mean of 95.38 (SEM 1.02) to 44.22 (1.05), mean SEF from 20.91 (1.19) to 14.14 (0.70) Hz, mean HRV from 37.1 (7.75) to 17.9 (3.6) bpm2 and ApEn from 0.90 (0.06) to 0.65 (0.04). Using logistic regression, the indices were compared both individually and in combination as to the power of distinguishing awake (at pre-induction) from asleep (at tube insertion) states. BIS had the best predictive power, with a sensitivity of 97.3%, specificity 94.4%, positive predictive value 94.7% and negative predictive value 97.1%. A combination of the indices conferred no additional predictive advantage. (+info)