bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amnestic Concentrations of Sevoflurane Inhibit Synaptic Plasticity of Hippocampal CA1 Neurons through γ-Aminobutyric Acid–mediated Mechanisms
Authors: Ishizeki Junko , Nishikawa Koichi , Kubo Kazuhiro , Saito Shigeru , Goto Fumio 
Published: March 2009

Background
The cellular mechanisms of anesthetic-induced amnesia are still poorly understood. The current study examined sevoflurane at various concentrations in the CA1 region of rat hippocampal slices for effects on excitatory synaptic transmission and on long-term potentiation (LTP), as a possible mechanism contributing to anesthetic-induced loss of recall.

Methods
Population spikes and field excitatory postsynaptic potentials were recorded using extracellular electrodes after electrical stimulation of Schaffer-collateral-commissural fiber inputs. Paired pulse facilitation was used as a measure of presynaptic effects of the anesthetic. LTP was induced using tetanic stimulation (100 Hz, 1 s). Sevoflurane at concentrations from amnestic (0.04 mm) to clinical concentrations (0.23-0.41 mm) were added to the perfusion solution.

Results
In the presence of 0.04 mm sevoflurane, the amplitude of population spikes was significantly depressed, and tetanic stimulation induced only posttetanic potentiation and then failure of LTP. These inhibitory effects were antagonized by bicuculline (10 microm), a gamma-aminobutyric acid type A receptor antagonist. Sevoflurane at 0.23-0.41 mm further depressed the amplitude of field excitatory postsynaptic potentials in a dose-dependent manner and completely blocked LTP. Bicuculline only partially antagonized 0.41 mm sevoflurane-induced profound inhibition of LTP. Sevoflurane at 0.23-0.41 mm, but not at 0.04 mm, significantly increased paired pulse facilitation, suggesting that sevoflurane has presynaptic actions to reduce glutamate release from nerve terminals.

Conclusions
The current study provides evidence that amnestic concentrations of sevoflurane inhibit LTP of hippocampal CA1 neurons through gamma-aminobutyric acid-mediated mechanisms, and these actions seem to account for the effects of amnestic sevoflurane on synaptic plasticity.
Isoflurane Reduces Excitability of Drosophila Larval Motoneurons by Activating a Hyperpolarizing Leak Conductance
Authors: Sandstrom David J. 
Published: March 2009

Background
Mechanisms of anesthetic-mediated presynaptic inhibition are incompletely understood. Isoflurane reduces presynaptic excitability at the larval Drosophila neuromuscular junction, slowing conduction velocity and depressing glutamate release. Mutations in the Para voltage-gated Na channel enhance anesthetic sensitivity of adult flies. Here, the author examines the role of para in anesthetic sensitivity and seeks to identify the conductance underlying presynaptic inhibition at this synapse.

Methods
Neuromuscular transmission was studied using a two-electrode voltage clamp, with isoflurane applied in physiologic saline. The relation between ionic conductances and presynaptic function was modeled in the Neuron Simulation Environment. Motoneuron ionic currents were monitored via whole cell recordings.

Results
Presynaptic inhibition by isoflurane was enhanced significantly in para mutants. Computer simulations of presynaptic actions of anesthetics indicated that each candidate target conductance would have diagnostic effects on the relation between latency and amplitude of synaptic currents. The experimental latency-amplitude relation for isoflurane most closely resembled activation of a simulated hyperpolarizing leak. Simulations indicated that increased isoflurane potency in para axons resulted from reduced excitability of mutant axons. In whole cell recordings, isoflurane activated a hyperpolarizing leak current. The effects of isoflurane at the neuromuscular junction were insensitive to low pH.

Conclusions
The effects of isoflurane on presynaptic excitability are mediated via an acid-insensitive inhibitory leak conductance. para mutations enhance the sensitivity of this anesthetic-modulated neural pathway by reducing axonal excitability. This work provides a link between anesthetic-sensitive leak currents and presynaptic function and has generated new tools for analysis of the function of this synapse.
Effect of Nitrous Oxide on Neurologic and Neuropsychological Function after Intracranial Aneurysm Surgery
Authors: McGregor Diana G. , Lanier William L. , Pasternak Jeffrey J. , Rusy Deborah A. , Hogan Kirk , Samra Satwant , Hindman Bradley , Todd Michael M. , Schroeder Darrell R. , Bayman Emine Ozgur , Clarke William , Torner James , Weeks Julie 
Published: March 2009

Background
Laboratory studies suggest that nitrous oxide augments brain injury after ischemia or hypoxia. The authors examined the relation between nitrous oxide use and outcomes using data from the Intraoperative Hypothermia for Aneurysm Surgery Trial.

Methods
The Intraoperative Hypothermia for Aneurysm Surgery Trial was a prospective randomized study of the impact of intraoperative hypothermia (temperature = 33 degrees C) versus normothermia (temperature = 36.5 degrees C) in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping. Anesthesia was dictated by a limited-options protocol with the use of nitrous oxide determined by individual anesthesiologists. All patients were assessed daily for 14 days after surgery or until hospital discharge. Neurologic and neuropsychological testing were conducted at 3 months after surgery. Outcome data were analyzed via both univariate tests and multivariate logistic regression analysis correcting for factors thought to influence outcome. An odds ratio (OR) greater than 1.0 denotes a worse outcome in patients receiving nitrous oxide.

Results
Outcome data were available for 1,000 patients, of which 373 received nitrous oxide. There was no difference between groups in the development of delayed ischemic neurologic deficit. At 3 months after surgery, there were no significant differences between groups in any outcome variable: Glasgow Outcome Score (OR, 0.84; 95% confidence interval [CI], 0.63-1.14; P = 0.268), National Institutes of Health Stroke Scale (OR, 1.29; 95% CI, 0.96-1.73; P = 0.087), Rankin Disability Score (OR, 0.84; 95% CI, 0.61-1.15; P = 0.284), Barthel Activities of Daily Living Index (OR, 1.01; 95% CI, 0.68-1.51; P = 0.961), or neuropsychological testing (OR, 1.26; 95% CI, 0.85-1.87; P = 0.252).

Conclusions
In a population of patients at risk for ischemic brain injury, nitrous oxide use had no overall beneficial or detrimental impact on neurologic or neuropsychological outcomes.
Cutaneous Amitriptyline in Human Volunteers
Authors: Dualé Christian , Daveau Julie , Cardot Jean-Michel , Boyer-Grand Anne , Schoeffler Pierre , Dubray Claude 
Published: March 2009

Background
Amitriptyline is effective in relieving neuropathic pain. Its site of action is thought to be supraspinal and spinal, but a peripheral effect on fibers is also suggested.

Methods
This double-blind study examined the effects of transcutaneous amitriptyline diluted in hydroalcoholic solution in healthy young male volunteers. Six treatments were randomly applied on different areas of the skin of the back: amitriptyline at 0 (vehicle), 25, 50, and 100 mm; saline (control); and lidocaine-prilocaine cream as a positive control. Up to 24 h after application, mechanical thresholds for touch and nociception, and thermal thresholds for cold, warm, and heat sensation were recorded for each area. Blood samples were collected to assess plasma levels of amitriptyline. A late recording of the tactile thresholds was performed 1 and 3 weeks after the treatment session.

Results
The thresholds for all sensations did not differ between the vehicle and saline. Lidocaine-prilocaine cream displayed a short-lasting anesthetic effect for all sensations, although this was not significant for warm sensation. Amitriptyline, at the three concentrations studied, induced a mild and short-lasting increase of the tactile and mechanical nociceptive thresholds. It significantly decreased cold thresholds (down to 21.8 degrees C, P = 0.01 vs. 27.5 degrees C for control) and heat thresholds (down to 40.1 degrees C, P = 0.004 vs. 43.4 degrees C for control). These two effects were no longer significant after the fourth hour of observation. Amitriptyline did not change warm thresholds. There was no apparent systemic absorption effect of the drug.

Conclusion
It is hypothesized that amitriptyline has a differential effect on different fiber structures.
Isoflurane Preconditioning Reduces the Rat NR8383 Macrophage Injury Induced by Lipopolysaccharide and Interferon γ
Authors: Xu Xuebing , Feng Jifeng , Zuo Zhiyi 
Published: March 2009

Background
Isoflurane exposure before an insult can reduce the insult-induced injury in various organs. This phenomenon is called isoflurane preconditioning. The authors hypothesize that isoflurane can precondition macrophages, cells that travel to all tissues and are important in the host defense and inflammation responses.

Methods
Rat NR8383 macrophages were pretreated with or without 1-3% isoflurane for 1 h at 30 min before they were incubated with or without 100 ng/ml lipopolysaccharide plus 50 U/ml interferon gamma for 24 h. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry was performed after cells were stained with annexin V and propidium iodide. Inducible nitric oxide synthase protein expression in macrophages was quantified by Western blotting.

Results
Lipopolysaccharide plus interferon gamma decreased cell viability by approximately 50%. This decrease was dose-dependently inhibited by aminoguanidine, an inducible nitric oxide synthase inhibitor. Lipopolysaccharide plus interferon gamma caused inducible nitric oxide synthase expression. This expression was inhibited by pretreatment with 2% but not 1% or 3% isoflurane. Isoflurane at 2% inhibited lipopolysaccharide plus interferon gamma-induced accumulation of nitrite, an oxidation product of nitric oxide. Pretreatment with 2% but not 1% or 3% isoflurane improved cell viability. Lipopolysaccharide plus interferon gamma increased the number of propidium iodide-positive staining cells. This increase was attenuated by 2% isoflurane pretreatment. The protective effect of 2% isoflurane was abolished by chelerythrine, calphostin C, or bisindolylmaleimide IX, protein kinase C inhibitors.

Conclusions
Lipopolysaccharide plus interferon gamma causes an inducible nitric oxide synthase-dependent macrophage injury. Isoflurane induces preconditioning effects that may be mediated by protein kinase C in macrophages.
Cardiac Arrests and Deaths Associated with Malignant Hyperthermia in North America from 1987 to 2006
Authors: Larach Marilyn Green , Brandom Barbara W. , Allen Gregory C. , Gronert Gerald A. , Lehman Erik B. 
Published: March 2009

Background
The authors determined associated cardiac arrest and death rates in cases from Canada and the United States as reported to The North American Malignant Hyperthermia (MH) Registry and analyzed factors associated with a higher risk of poor outcomes.

Methods
The authors searched the database for AMRA (adverse metabolic/musculoskeletal reaction to anesthesia) reports with inclusion criteria as follows: event date between January 1, 1987, and December 31, 2006; "very likely" or "almost certain" MH as ranked by MH Clinical Grading Scale; location in Canada or the United States; and one or more anesthetic agents given. The exclusion criterion was a pathologic condition other than MH independently judged by the authors. Severe MH outcomes were analyzed as regards clinical history and presentation, using Wilcoxon rank sum tests for continuous variables and Pearson exact chi-square tests for categorical variables. A Bonferroni correction adjusted for multiple comparisons.

Results
Of 291 events, 8 (2.7%) resulted in cardiac arrests and 4 (1.4%) resulted in death. The median age in cases of cardiac arrest/death was 20 yr (range, 2-31 yr). Associated factors were muscular build (odds ratio, 18.7; P = 0.0016) and disseminated intravascular coagulation (odds ratio, 49.7; P < 0.0001). Increased risk of cardiac arrest/death was related to a longer time period between anesthetic induction and maximum end-tidal carbon dioxide (216 vs. 87 min; P = 0.003). Unrelated factors included patient or family history, anesthetic management, and the MH episode.

Conclusions
Modern US anesthetic practice did not prevent MH-associated cardiac arrest and death in predominantly young, healthy patients undergoing low- to intermediate-risk surgical procedures.
Additive Interaction of the Cannabinoid Receptor I Agonist Arachidonyl-2-chloroethylamide with Etomidate in a Sedation Model in Mice
Authors: Meybohm Patrick , Brand Philipp-Alexander , Ufer Mike , Thiemann Florian , Steinfath Markus , Paris Andrea , Scholz Jens , Bein Berthold 
Published: March 2009

Background
Both propofol and volatile anesthetics have been reported to interact with the endocannabinoid system. The purpose of this study was to evaluate the effect of selective agonists for cannabinoid receptor types 1 and 2 on etomidate-induced sedation.

Methods
A controlled, blinded, experimental study was performed in 20 mice that received intraperitoneal injections of etomidate, the cannabinoid1 receptor agonist arachidonyl-2-chloroethylamide (ACEA), the cannabinoid2 receptor agonist JWH 133 alone, and both ACEA and JWH 133 combined with etomidate. The cannabinoid1 receptor antagonist AM 251 and the cannabinoid2 receptor antagonist AM 630 were administered 10 min before the delivery of ACEA and JWH 133, respectively. Each drug combination was applied to 6-8 mice of these 20 study animals. Sedation was monitored by a Rota-Rod (Ugo Basile, Comerio, Italy). Isobolographic analysis was used for evaluation of pharmacologic interaction.

Results
Single drug administration of etomidate and ACEA produced dose- and time-dependent decreased time on the Rota-Rod (P < 0.05). No sedative effect was seen after JWH 133. Etomidate-induced sedation was significantly increased and prolonged with ACEA (P < 0.05), but not with JWH 133. Isobolographic analysis revealed an additive interaction between ACEA and etomidate that was antagonized by the cannabinoid1 receptor antagonist AM 251. The cannabinoid1 receptor antagonist had no effect on etomidate alone.

Conclusions
Etomidate-induced sedation was increased and prolonged by activation of the cannabinoid1 receptor, but not of the cannabinoid2 receptor, in mice. However, this interaction was only additive.
Inhaled Hydrogen Sulfide
Authors: Volpato Gian Paolo , Searles Robert , Yu Binglan , Scherrer-Crosbie Marielle , Bloch Kenneth D. , Ichinose Fumito , Zapol Warren M. 
Published: March 2009

Background
Breathing hydrogen sulfide (H2S) has been reported to induce a suspended animation-like state with hypothermia and a concomitant metabolic reduction in rodents. However, the impact of H2S breathing on cardiovascular function remains incompletely understood. In this study, the authors investigated the cardiovascular and metabolic effects of inhaled H2S in a murine model.

Methods
The impact of breathing H2S on cardiovascular function was examined using telemetry and echocardiography in awake mice. The effects of breathing H2S on carbon dioxide production and oxygen consumption were measured at room temperature and in a warmed environment.

Results
Breathing H2S at 80 parts per million by volume at 27 degrees C ambient temperature for 6 h markedly reduced heart rate, core body temperature, respiratory rate, and physical activity, whereas blood pressure remained unchanged. Echocardiography demonstrated that H2S exposure decreased both heart rate and cardiac output but preserved stroke volume. Breathing H2S for 6 h at 35 degrees C ambient temperature (to prevent hypothermia) decreased heart rate, physical activity, respiratory rate, and cardiac output without altering stroke volume or body temperature. H2S breathing seems to induce bradycardia by depressing sinus node activity. Breathing H2S for 30 min decreased whole body oxygen consumption and carbon dioxide production at either 27 degrees or 35 degrees C ambient temperature. Both parameters returned to baseline levels within 10 min after the cessation of H2S breathing.

Conclusions
Inhalation of H2S at either 27 degrees or 35 degrees C reversibly depresses cardiovascular function without changing blood pressure in mice. Breathing H2S also induces a rapidly reversible reduction of metabolic rate at either body temperature.
Spinal Microglial and Perivascular Cell Cannabinoid Receptor Type 2 Activation Reduces Behavioral Hypersensitivity without Tolerance after Peripheral Nerve Injury
Authors: Romero-Sandoval Alfonso , Nutile-McMenemy Nancy , DeLeo Joyce A. 
Published: March 2009

Background
Cannabinoids induce analgesia by acting on cannabinoid receptor (CBR) types 1 and/or 2. However, central nervous system side effects and antinociceptive tolerance from CBR1 limit their clinical use. CBR2 exist on spinal glia and perivascular cells, suggesting an immunoregulatory role of these receptors in the central nervous system. Previously, the authors showed that spinal CBR2 activation reduces paw incision hypersensitivity and glial activation. This study tested whether CBR2 are expressed in glia and whether their activation would induce antinociception, glial inhibition, central side effects, and antinociceptive tolerance in a neuropathic rodent pain model.

Methods
Rats underwent L5 spinal nerve transection or sham surgery, and CBR2 expression and cell localization were assessed by immunohistochemistry. Animals received intrathecal injections of CBR agonists and antagonists, and mechanical withdrawal thresholds and behavioral side effects were assessed.

Results
Peripheral nerve transection induced hypersensitivity, increased expression of CR3/CD11b and CBR2, and reduced ED2/CD163 expression in the spinal cord. The CBR2 were localized to microglia and perivascular cells. Intrathecal JWH015 reduced peripheral nerve injury hypersensitivity and CR3/CD11b expression and increased ED2/CD163 expression in a dose-dependent fashion. These effects were prevented by intrathecal administration of the CBR2 antagonist (AM630) but not the CBR1 antagonist (AM281). JWH015 did not cause behavioral side effects. Chronic intrathecal JWH015 treatment did not induce antinociceptive tolerance.

Conclusions
These data indicate that intrathecal CBR2 agonists may provide analgesia by modulating the spinal immune response and microglial function in chronic pain conditions without inducing tolerance and neurologic side effects.
Effects of Ropivacaine on Action Potential Configuration and Ion Currents in Isolated Canine Ventricular Cardiomyocytes
Authors: Szabó Adrienn , Szentandrássy Norbert , Birinyi Péter , Horváth Balázs , Szabó Gergely , Bányász Tamás , Márton Ildikó , Magyar János , Nánási Péter P. 
Published: March 2009

Background
Despite the widespread clinical application of ropivacaine, there is little information on the cellular cardiac effects of the drug. In the current study, therefore, the concentration-dependent effects of ropivacaine on action potential morphology and the underlying ion currents were studied and compared with those of bupivacaine in isolated canine ventricular cardiomyocytes.

Methods
Action potentials were recorded from the enzymatically dispersed cells using sharp microelectrodes. Conventional patch clamp and action potential voltage clamp arrangements were used to study the effects of ropivacaine on transmembrane ion currents.

Results
Ropivacaine induced concentration- and frequency-dependent changes in action potential configuration, including shortening of the action potentials, reduction of their amplitude and maximum velocity of depolarization, suppression of early repolarization, and depression of plateau. Reduction in maximum velocity of depolarization was characterized with an EC50 value of 81 +/- 7 microm at 1 Hz. Qualitatively similar results were obtained with bupivacaine (EC50 = 47 +/- 3 microm). Under voltage clamp conditions, a variety of ion currents were blocked by ropivacaine: L-type calcium current (EC50 = 263 +/- 67 microm), transient outward current (EC50 = 384 +/- 75 microm), inward rectifier potassium current (EC50 = 372 +/- 35 microm), rapid delayed rectifier potassium current (EC50 = 303 +/- 47 microm), and slow delayed rectifier potassium current (EC50 = 106 +/- 18 microm).

Conclusions
Ropivacaine, similarly to bupivacaine, can modify cardiac action potentials and the underlying ion currents at concentrations higher than the usual therapeutic range. However, in cases of overdose, cardiac complications may be anticipated both during and after anesthesia due to the blockade of various ion currents.
Randomized Controlled Trial Comparing Adaptive-support Ventilation with Pressure-regulated Volume-controlled Ventilation with Automode in Weaning Patients after Cardiac Surgery
Authors: Gruber Pascale C. , Gomersall Charles D. , Leung Patricia , Joynt Gavin M. , Ng Siu Keung , Ho Ka-man , Underwood Malcolm J. 
Published: March 2009

Background
Adaptive-support ventilation (ASV) is a minute ventilation-controlled mode governed by a closed-loop algorithm. With ASV, tidal volume and respiratory rate are automatically adjusted to minimize work of breathing. Studies indicate that ventilation in ASV enables more rapid weaning. The authors conducted a randomized controlled trial to determine whether ventilation in ASV results in a shorter time to extubation than pressure-regulated volume-controlled ventilation with automode (PRVCa) after cardiac surgery.

Methods
Fifty patients were randomly assigned to ASV or PRVCa after elective coronary artery bypass grafting. Respiratory weaning progressed through three phases: phase 1 (controlled ventilation), phase 2 (assisted ventilation), and phase 3 (T-piece trial), followed by extubation. The primary outcome was duration of intubation (sum of phases 1-3). Secondary outcomes were duration of mechanical ventilation (sum of phases 1 and 2), number of arterial blood gas samples, and manual ventilator setting changes made before extubation.

Results
Forty-eight patients completed the study. The median duration of intubation was significantly shorter in the ASV group than in the PRVCa group (300 [205-365] vs. 540 [462-580] min; P < 0.05). This difference was due to a reduction in the duration of mechanical ventilation (165 [120-195] vs. 480 [360-510] min; P < 0.05). There were no significant differences between the ASV and PRVCa groups in the number of arterial blood gas samples taken or manual ventilator setting changes made.

Conclusions
ASV is associated with earlier extubation, without an increase in clinician intervention, when compared with PRVCa in patients undergoing uncomplicated cardiac surgery.