bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contrasting Synaptic Actions of the Inhalational General Anesthetics Isoflurane and Xenon
Authors: de Sousa Sara L. M. , Dickinson Robert , Lieb William R. , Franks Nicholas P. 
Published: August 2004

Background
The mechanisms by which the inhalational general anesthetics isoflurane and xenon exert their effects are unknown. Moreover, there have been surprisingly few quantitative studies of the effects of these agents on central synapses, with virtually no information available regarding the actions of xenon.

Methods
The actions of isoflurane and xenon on gamma-aminobutyric acid-mediated (GABAergic) and glutamatergic synapses were investigated using voltage-clamp techniques on autaptic cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks.

Results
Isoflurane exerts its greatest effects on GABAergic synapses, causing a marked increase in total charge transfer (by approximately 70% at minimum alveolar concentration) through the inhibitory postsynaptic current. This effect is entirely mediated by an increase in the slow component of the inhibitory postsynaptic current. At glutamatergic synapses, isoflurane has smaller effects, but it nonetheless significantly reduces the total charge transfer (by approximately 30% at minimum alveolar concentration) through the excitatory postsynaptic current, with the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components being roughly equally sensitive. Xenon has no measurable effect on GABAergic inhibitory postsynaptic currents or on currents evoked by exogenous application of GABA, but it substantially inhibits total charge transfer (by approximately 60% at minimum alveolar concentration) through the excitatory postsynaptic current. Xenon selectively inhibits the NMDA receptor-mediated component of the current but has little effect on the AMPA/kainate receptor-mediated component.

Conclusions
For both isoflurane and xenon, the most important targets appear to be postsynaptic. The authors' results show that isoflurane and xenon have very different effects on GABAergic and glutamatergic synaptic transmission, and this may account for their differing pharmacologic profiles.
Effects of Intravenous Anesthetic Agents on Glutamate Release
Authors: Buggy Donal J. , Nicol Beverley , Rowbotham David J. , Lambert David G. 
Published: August 2004

Background
Many anesthetic agents are known to enhance the alpha1beta2gamma2S gamma-aminobutyric acid type A (GABAA) chloride current; however, they also depress excitatory neurotransmission. The authors evaluated two hypotheses: intravenous anesthetic agents inhibit glutamate release and any observed inhibition may be secondary to GABAA receptor activation.

Methods
Cerebrocortical slices were prepared from Wistar rats. After perfusion in oxygenated Krebs buffer for 60 min at 37 degrees C, samples for glutamate assay were obtained at 2-nmin intervals. After 6 min, a 2-min pulse of 46 mM K+ was applied to the slices (S1); this was repeated after 30 min (S2). Bicuculline (1-100 microM) was applied when the S1 response returned to basal level, and 10 min later, thiopental (1-300 micro/M), propofol (10 microM), or ketamine (30 microM) were also applied until the end of S2. Perfusate glutamate concentrations were measured fluorometrically, and the area under the glutamate release curves was expressed as a ratio (S2/S1).

Results
Potassium (46 mM) evoked a monophasic release of glutamate during S1 and S2, with a mean control S2/S1 ratio of 1.07 +/- 0.33 (mean +/- SD, n = 96). Ketamine and thiopental produced a concentration-dependent inhibition of K+-evoked glutamate release with half-maximum inhibition of release values of 18.2 and 10.9 /microM, respectively. Release was also inhibited by propofol. Bicuculline produced a concentration dependent reversal of thiopental inhibition of glutamate release with a half-maximum reversal of the agonist effect of 10.3 microM. Bicuculline also reversed the effects of propofol but not those of ketamine.

Conclusions
The authors' data indicate that thiopental, propofol, and ketamine inhibit K+-evoked glutamate release from rat cerebrocortical slices. The inhibition produced by thiopental and propofol is mediated by activation of GABAA receptors, revealing a subtle interplay between GABA-releasing (GABAergic) and glutamatergic transmission in anesthetic action.
Attenuation of Ascending Nociceptive Signals to the Rostroventromedial Medulla Induced by a Novel α2-Adrenoceptor Agonist, MPV-2426, following Intrathecal Application in Neuropathic Rats
Authors: Pertovaara Antti , Wei Hong 
Published: August 2004

Background
In the current study, the potency and spread of the antinociception induced by MPV-2426, a novel alpha2-adrenoceptor agonist, was characterized in neuropathic and non-neuropathic animals.

Methods
Neuropathy was induced by unilateral ligation of two spinal nerves in the rat. After lumbar intrathecal or systemic administration of MPV-2426, thermally and mechanically evoked responses of nociceptive neurons of the rostroventromedial medulla were recorded during pentobarbitone anesthesia. To obtain a behavioral correlate of neurophysiologic findings, nocifensor reflex responses evoked by thermal and mechanical stimuli were assessed in unanesthetized neuropathic and control animals.

Results
After intrathecal administration, MPV-2426 and dexmedetomidine produced a dose-related antinociceptive effect, independent of the submodality of the noxious test stimulus or the pathophysiologic condition. This antinociceptive effect was spatially restricted to the inputs from the lower half of the body, and it was reversed by atipamezole, an alpha2-adrenoceptor antagonist. After systemic administration in non-neuropathic animals, MPV-2426 had no antinociceptive effect on responses to rostroventromedial medulla neurons, whereas systemically administered dexmedetomidine produced a dose-related suppression of nociceptive signals to the rostroventromedial medulla, independent of the site of test stimulation. In a behavioral study, intrathecal MPV-2426 produced a dose-dependent suppression of nocifensor responses evoked by noxious mechanical or heat stimuli, whereas systemic administration of MPV-2426 had no effects.

Conclusions
Intrathecal MPV-2426 has spatially limited antinociceptive properties in neuropathic and non-neuropathic conditions because of its action on spinal alpha2-adrenoceptors. These properties may be advantageous when designing therapy for spatially restricted pain problems.
Volatile Anesthetics Differentially Affect Immunostimulated Expression of Inducible Nitric Oxide Synthase
Authors: Tschaikowsky Klaus , Ritter Jörg , Schröppel Klaus , Kühn Matthias 
Published: August 2004

Background
Nitric oxide released by inducible nitric oxide synthase (iNOS) plays an important role in immune responses and systemic vasodilation in septic shock. Volatile anesthetics have been reported to interfere with signal transduction and gene expression. We studied the effect of volatile anesthetics on activity and expression of iNOS and potential mechanisms of action.

Methods
Nitrite release and iNOS expression were determined using the Griess reaction and Western and Northern blot techniques, respectively, in J774 murine macrophages stimulated with lipopolysaccharide and gamma-interferon in the absence and presence of various concentrations (0.25-2.0 minimum alveolar concentration [MAC]) of volatile anesthetics (i.e., halothane, enflurane, isoflurane, desflurane). Furthermore, potential interference of volatile anesthetics with specific signal transduction pathways was investigated.

Results
All volatile anesthetics, studied in a time- and dose-dependent manner, suppressed nitrite production and iNOS expression in J774 macrophages stimulated by lipopolysaccharide or gamma-interferon at clinically relevant concentrations. The inhibition was completely antagonized by ionomycin but unaffected by diacylglycerol, phorbol myristate acetate, and C2-ceramide. In contrast, in cells costimulated by lipopolysaccharide plus gamma-interferon, volatile anesthetics significantly increased nitrite production and iNOS expression independent of ionomycin and other mediators studied.

Conclusions
Volatile anesthetics strongly reduced the mRNA and protein levels of iNOS and NOS activity after a single stimulation with lipopolysaccharide or gamma-interferon, most likely by attenuating intracellular calcium increase. Costimnulation with lipopolysaccharide plus gamma-interferon, however, results in maximum iNOS expression and activity, which are no longer inhibited but are potentiated by volatile anesthetics by unidentified mechanisms.
Antiallodynic Effect of Intrathecal Gabapentin and Its Interaction with Clonidine in a Rat Model of Postoperative Pain
Authors: Cheng Jen-Kun , Pan Hui-Lin , Eisenach James C. 
Published: August 2004

Background
Systemic administration of gabapentin was shown previously to attenuate mechanical allodynia in a rat model of postoperative pain. Because intrathecal administration of gabapentin is effective in other hypersensitivity states, the authors tested its effect in the postoperative model, its interaction with another antiallodynic agent (clonidine), and a possible mechanism of gabapentin action (entry into sites of action via an L-amino acid transporter).

Methods
Male Sprague-Dawley rats were anesthetized with halothane, and an incision of the plantaris muscle of right hind paw induced punctate mechanical allodynia. Withdrawal threshold to von Frey filament application near the incision site was determined before and 2 h after surgery. Then, an intrathecal injection was performed and thresholds were determined every 30 min for 3 h thereafter.

Results
Paw incision induced a mechanical hypersensitivity (mechanical threshold > 25 g before incision and < 5 g after). Intrathecal gabapentin dose-dependently (10-100 microg) reduced mechanical allodynia. Intrathecal injection of an inhibitor of L-amino acid transporters or a competitor for this transporter, L-leucine, did not reverse the intrathecal effect of gabapentin. The ED50 of intrathecal gabapentin, clonidine, and their combination were 51, 31, and 9 microg, respectively, and isobolographic analysis showed synergy between gabapentin and clonidine.

Conclusions
Intrathecal gabapentin is effective against tactile allodynia that occurs after paw incision, and interacts synergistically with clonidine. Unlike results in vitro, gabapentin does not obligatorily need to enter cells via the L-amino acid transporter mechanism to achieve its effects in vivo.
Subunit-dependent Inhibition of Human Neuronal Nicotinic Acetylcholine Receptors and Other Ligand-gated Ion Channels by Dissociative Anesthetics Ketamine and Dizocilpine
Authors: Yamakura Tomohiro , Chavez-Noriega Laura E. , Harris R. Adron 
Published: August 2004

Unlabelled
Background The neuronal mechanisms responsible for dissociative anesthesia remain controversial. N-methyl-D-aspartate (NMDA) receptors are inhibited by ketamine and related drugs at concentrations lower than those required for anesthetic effects. Thus, the authors studied whether ligand-gated ion channels other than NMDA receptors might display a sensitivity to ketamine and dizocilpine that is consistent with concentrations required for anesthesia.

Methods
Heteromeric human neuronal nicotinic acetylcholine receptors (hnAChR channels alpha2beta2, alpha2beta4, alpha3beta2, alpha3beta4, alpha4beta2 and alpha4beta4), 5-hydroxytryptamine3 (5-HT3), alpha1beta2gamma2S gamma-aminobutyric acid type A (GABAA) and alpha1 glycine receptors were expressed in Xenopus oocytes, and effects of ketamine and dizocilpine were studied using the two-electrode voltage-clamp technique.

Results
Both ketamine and dizocilpine inhibited hnAChRs in a noncompetitive and voltage-dependent manner. Receptors containing beta1 subunits were more sensitive to ketamine and dizocilpine than those containing beta2 subunits. The inhibitor concentration for half-maximal response (IC50) values for ketamine of hnAChRs composed of beta4 subunits were 9.5-29 microM, whereas those of beta2 subunits were 50-92 microM. Conversely, 5-HT3 receptors were inhibited only by concentrations of ketamine and dizocilpine higher than the anesthetic concentrations. This inhibition was mixed (competitive/noncompetitive). GABAA and glycine receptors were very resistant to dissociative anesthetics.

Conclusions
Human nAChRs are inhibited by ketamine and dizocilpine at concentrations possibly achieved in vivo during anesthesia in a subunit-dependent manner, with beta subunits being more critical than alpha subunits. Conversely, 5-HT3, GABAA, and glycine receptors were relatively insensitive to dissociative anesthetics.
Blockade of Adenosine Triphosphate–sensitive Potassium Channels by Thiamylal in Rat Ventricular Myocytes
Authors: Tsutsumi Yasuo , Oshita Shuzo , Kitahata Hiroshi , Kuroda Yasuhiro , Kawano Takashi , Nakaya Yutaka 
Published: August 2004

Background
The adenosine triphosphate (ATP)-sensitive potassium (KATP) channels protect myocytes during ischemia and reperfusion. This study investigated the effects of thiamylal on the activities of KATP channels in isolated rat ventricular myocytes during simulated ischemia.

Methods
Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. Membrane currents were recorded using patch-clamp techniques. In the cell-attached configuration, KATP channel currents were assessed before and during activation of these channels by 2,4-dinitrophenol and after administration of 25, 50, and 100 mg/l thiamylal. The open probability was determined from current-amplitude histograms. In the inside-out configuration, the current-voltage relation was obtained before and after the application of thiamylal (50 mg/1).

Results
In the cell-attached configuration, 2,4-dinitrophenol caused frequent channel opening. 2,4-Dinitrophenol-induced channel activities were reduced significantly by glibenclamide, suggesting that the channels studied were KATP channels. Open probability of KATP channels was reduced by thiamylal in a concentration-dependent manner. KATP channels could be activated in the inside-out configuration because of the absence of ATP. Thiamylal inhibited KATP channel activity without changing the single-channel conductance.

Conclusions
The results obtained in this study indicate that thiamylal inhibits KATP channel activities in cell-attached and inside-out patches, suggesting a direct action of this drug on these channels.
Modeling the Uncertainty of Surgical Procedure Times
Authors: Strum David P. , May Jerrold H. , Vargas Luis G. 
Published: August 2004

Background
Medical institutions are under increased economic pressure to schedule elective surgeries efficiently to contain the costs of surgical services. Surgical scheduling is complicated by variability inherent in the duration of surgical procedures. Modeling that variability, in turn, provides a mechanism to generate accurate time estimates. Accurate time estimates are important operationally to improve operating room utilization and strategically to identify surgeons, procedures, or patients whose duration of surgeries differ from what might be expected.

Methods
The authors retrospectively studied 40,076 surgical cases (1,580 Current Procedural Terminology-anesthesia combinations, each with a case frequency of five or more) from a large teaching hospital, and attempted to determine whether the distribution of surgical procedure times more closely fit a normal or a log-normal distribution. The authors tested goodness-of-fit to these data for both models using the Shapiro-Wilk test. Reasons, in practice, the Shapiro-Wilk test may reject the fit of a log-normal model when in fact it should be retained were also evaluated.

Results
The Shapiro-Wilk test indicates that the log-normal model is superior to the normal model for a large and diverse set of surgeries. Goodness-of-fit tests may falsely reject the log-normal model during certain conditions that include rounding errors in procedure times, large sample sizes, untrimmed outliers, and heterogeneous mixed populations of surgical procedure times.

Conclusions
The authors recommend use of the log-normal model for predicting surgical procedure times for Current Procedural Terminology-anesthesia combinations. The results help to legitimize the use of log transforms to normalize surgical procedure times before hypothesis testing using linear statistical models or other parametric statistical tests to investigate factors affecting the duration of surgeries.
Prediction of Difficult Mask Ventilation
Authors: Langeron Olivier , Masso Eva , Huraux Catherine , Guggiari Michel , Bianchi André , Coriat Pierre , Riou Bruno 
Published: August 2004

Background
Maintenance of airway patency and oxygenation are the main objectives of face-mask ventilation. Because the incidence of difficult mask ventilation (DMV) and the factors associated with it are not well known, we undertook this prospective study.

Methods
Difficult mask ventilation was defined as the inability of an unassisted anesthesiologist to maintain the measured oxygen saturation as measured by pulse oximetry > 92% or to prevent or reverse signs of inadequate ventilation during positive-pressure mask ventilation under general anesthesia. A univariate analysis was performed to identify potential factors predicting DMV, followed by a multivariate analysis, and odds ratio and 95% confidence interval were calculated.

Results
A total of 1,502 patients were prospectively included. DMV was reported in 75 patients (5%; 95% confidence interval, 3.9-6.1%), with one case of impossible ventilation. DMV was anticipated by the anesthesiologist in only 13 patients (17% of the DMV cases). Body mass index, age, macroglossia, beard, lack of teeth, history of snoring, increased Mallampati grade, and lower thyromental distance were identified in the univariate analysis as potential DMV risk factors. Using a multivariate analysis, five criteria were recognized as independent factors for a DMV (age older than 55 yr, body mass index > 26 kg/m2, beard, lack of teeth, history of snoring), the presence of two indicating high likelihood of DMV (sensitivity, 0.72; specificity, 0.73).

Conclusion
In a general adult population, DMV was reported in 5% of the patients. A simple DMV risk score was established. Being able to more accurately predict DMV may improve the safety of airway management.
Citrate Storage Affects Thrombelastograph®Analysis
Authors: Camenzind Vladimir , Bombeli Thomas , Seifert Burkhardt , Jamnicki Marina , Popovic Dragoljub , Pasch Thomas , Spahn Donat R. 
Published: August 2004

Background
Thrombelastograph analysis (TEG) is used to evaluate blood coagulation. Ideally, whole blood is immediately processed. If impossible, blood may be citrated and assessed after recalcification. No data describe the effect of such treatment and storage on TEG parameters.

Methods
Three studies were performed in 90 surgical patients. In 30 patients, blood was citrated (1:10, 0. 129 M) and recalcified (20 microl 2 M CaCl2 to 340 microl citrated blood), and TEG was performed with native blood and after recalcification after 0, 15, and 30 min of citrate storage. In another 30 patients, TEG was performed with citrated blood recalcified immediately and after 1-72 h storage. In a third study, thrombin-antithrombin complex, prothrombin fragment 1+2, and beta-thromboglobulin were measured (using enzyme-linked immunoabsorbant assay tests) at corresponding time points. Data were compared using repeated-measures analysis of variance and post hocpaired t tests.

Results
TEG parameters were different in recalcified citrated blood compared with native blood (P < 0.05) and changed significantly during 30-min (P < 0.025) and 72-h (P < 0.001) citrate storage. TEG parameters measured between 1 and 8 h of citrate storage were stable. Thrombin-antithrombin complex and prothrombin fragment 1+2 values were not elevated in native blood. After 30 min of citrate storage a gradual thrombin activation was observed, as evidenced by increasing thrombin-antithrombin complex and prothrombin fragment 1+2 values (P < 0.05). beta-Thromboglobulin level was increased after 2 and 8 h of citrate storage (P < 0.01).

Conclusions
Analysis of native blood yields the most reliable TEG results. Should immediate TEG processing not be possible, citrated blood may be used if recalcified after 1-8 h.
Neural Mechanisms of Antinociceptive Effects of Hypnosis
Authors: Faymonville Marie Elisabeth , Laureys Steven , Degueldre Christian , DelFiore Guy , Luxen André , Franck Georges , Lamy Maurice , Maquet Pierre 
Published: August 2004

Background
The neural mechanisms underlying the modulation of pain perception by hypnosis remain obscure. In this study, we used positron emission tomography in 11 healthy volunteers to identify the brain areas in which hypnosis modulates cerebral responses to a noxious stimulus.

Methods
The protocol used a factorial design with two factors: state (hypnotic state, resting state, mental imagery) and stimulation (warm non-noxious vs. hot noxious stimuli applied to right thenar eminence). Two cerebral blood flow scans were obtained with the 15O-water technique during each condition. After each scan, the subject was asked to rate pain sensation and unpleasantness. Statistical parametric mapping was used to determine the main effects of noxious stimulation and hypnotic state as well as state-by-stimulation interactions (i.e., brain areas that would be more or less activated in hypnosis than in control conditions, under noxious stimulation).

Results
Hypnosis decreased both pain sensation and the unpleasantness of noxious stimuli. Noxious stimulation caused an increase in regional cerebral blood flow in the thalamic nuclei and anterior cingulate and insular cortices. The hypnotic state induced a significant activation of a right-sided extrastriate area and the anterior cingulate cortex. The interaction analysis showed that the activity in the anterior (mid-)cingulate cortex was related to pain perception and unpleasantness differently in the hypnotic state than in control situations.

Conclusions
Both intensity and unpleasantness of the noxious stimuli are reduced during the hypnotic state. In addition, hypnotic modulation of pain is mediated by the anterior cingulate cortex.