bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversal of Neuromusclar Blockade and Simultaneous Increase in Plasma Rocuronium Concentration after the Intravenous Infusion of the Novel Reversal Agent Org 25970
Authors: Epemolu Ola , Bom Anton , Hope Frank , Mason Rona 
Published: November 2003

Background
The purpose of this study was to determine the changes in the plasma concentration of rocuronium and the reversal of its neuromuscular blockade after the intravenous infusion of Org 25969, the novel neuromuscular block-reversal agent, in anesthetized guinea pigs.

Methods
Rocuronium was infused for 1 h at a rate of 12-19 nmol.kg-1.min-1 to produce a steady-state 90% neuromuscular block. After 30 min, a concomitant infusion of either the reversal agent Org 25969 at a rate of 50 nmol.kg-1.min-1 or an infusion of an equivalent volume of saline was started. The time course of plasma concentrations of rocuronium was determined by use of liquid chromatography-mass spectrometry/mass spectrometry.

Results
In both treatment groups, a steady-state plasma concentration of rocuronium was obtained after 30 min. In the saline-treated group, the plasma concentration of rocuronium and depth of block remained constant. In the Org 25969 group, neuromuscular block was reversed while the rocuronium infusion was ongoing. Simultaneously, an increase in the total plasma concentration of rocuronium (free and complexed) was observed, even though the infusion rate of rocuronium was not changed. Compared with the saline-treated group, a small increase in the postmortem bladder concentration of rocuronium was detected.

Conclusions
The authors propose that the capture of rocuronium by Org 25969 causes the rapid reversal of neuromuscular block. The reversal can be explained by the rapid transfer of free rocuronium from the effect compartment (neuromuscular junction) to the central compartment, in which it is bound to Org 25969. This explains the increase in total plasma concentration of rocuronium (free and bound to Org 25969).
Bacterial Reduction by Cell Salvage Washing and Leukocyte Depletion Filtration
Authors: Waters Jonathan H. , Tuohy Marion J. , Hobson Donna F. , Procop Gary 
Published: November 2003

Background
Blood conservation techniques are being increasingly used because of the increased cost and lack of availability of allogeneic blood. Cell salvage offers great blood savings opportunities but is thought to be contraindicated in a number of areas (e.g., blood contaminated with bacteria). Several outcome studies have suggested the safety of this technique in trauma and colorectal surgery, but many practitioners are still hesitant to apply cell salvage in the face of frank bacterial contamination. This study was undertaken to assess the efficacy of bacterial removal when cell salvage was combined with leukocyte depletion filtration.

Methods
Expired packed erythrocytes were obtained and inoculated with a fixed amount of a stock bacteria (Escherichia coli American Type Culture Collections [ATCC] 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, or Bacteroides fragilis ATCC 25285) in amounts ranging from 2,000 to 4,000 colony forming units/ml. The blood was processed via a cell salvage machine. The washed blood was then filtered using a leukocyte reduction filter. The results for blood taken during each step of processing were compared using a repeated-measures design.

Results
Fifteen units of blood were contaminated with each of the stock bacteria. From the prewash sample to the postfiltration sample, 99.0%, 99.6%, 100%, and 97.6% of E. coli, S. aureus, P. aeruginosa, and B. fragilis were removed, respectively.

Discussion
Significant but not complete removal of contaminating bacteria was seen. An increased level of patient safety may be added to cell salvage by including a leukocyte depletion filter when salvaging blood that might be grossly contaminated with bacteria.
Ca2+- and Myosin Phosphorylation–independent Relaxation by Halothane in K+-depolarized Rat Mesenteric Arteries
Authors: Tsuneyoshi Isao , Zhang Dongya , Boyle Walter A. 
Published: November 2003

Background
Volatile anesthetics inhibit vascular smooth muscle contraction, but the mechanisms responsible are uncertain. In this study, the effects of halothane on Ca2+ signaling and Ca2+ activation of contractile proteins were examined in high K+-depolarized smooth muscle from rat mesenteric resistance arteries.

Methods
Vessels were cannulated and held at a constant transmural pressure (40 mmHg). Image analysis and microfluorimetry were used to simultaneously measure vessel diameter and smooth muscle intracellular [Ca2+] concentration ([Ca2+]i). Myosin light chain (MLC) phosphorylation was measured using the Western blotting technique.

Results
Step increases in extracellular [Ca2+] concentration (0-10 mM) in high K+ (40 mM)-depolarized smooth muscle produced incremental increases in [Ca2+]i, MLC phosphorylation, and contraction. Halothane (0.5-4.5%) inhibited contraction in a concentration-dependent manner, but the decrease in [Ca2+]i was small, and there was a marked shift in the [Ca2+]i-contraction relationship to the right, indicating an important Ca2+ desensitizing effect. Halothane (0.5-4.5%) did not affect MLC phosphorylation or the [Ca2+]-MLC phosphorylation relationship, but the MLC phosphorylation-contraction relationship was also shifted rightward, indicating an "MLC phosphorylation" desensitizing effect. In contrast, control relaxations produced by the Ca2+ channel blocker nifedipine were accompanied by decreases in both [Ca2+]i and MLC phosphorylation, and nifedipine had no affect on the [Ca2+]i-contraction, [Ca2+]i-MLC phosphorylation, and MLC phosphorylation-contraction relationships.

Conclusions
In high K+-depolarized vascular smooth muscle, halothane relaxation is largely mediated by a Ca2+ and MLC phosphorylation desensitizing effect. These results suggest that the relaxing action of halothane is independent of the classic Ca2+-induced myosin phosphorylation contraction mechanism.
Thoracic Epidural Anesthesia Attenuates Hemorrhage-induced Impairment of Intestinal Perfusion in Rats
Authors: Adolphs Jörn , Schmidt Diego K. , Mousa Shaaban A. , Kamin Britta , Korsukewitz Ines , Habazettl Helmut , Schäfer Michael , Welte Martin 
Published: November 2003

Background
During hemorrhagic hypotension, sympathetic vasoconstriction crucially contributes to gut mucosal damage. Sympathetic blockade by thoracic epidural anesthesia has been shown to increase mucosal microvascular perfusion and to improve survival after severe hemorrhage in laboratory animals. This study investigates the effects of thoracic epidural anesthesia on intestinal microvascular perfusion during hemorrhagic hypotension in rats.

Methods
In 32 anesthetized Sprague-Dawley rats either lidocaine 2% (thoracic epidural anesthesia) or normal saline (control) was infused via thoracic epidural catheters. Hemorrhagic hypotension (mean arterial pressure 30 mmHg for 60 min) was induced by withdrawal of blood, which was subsequently retransfused for resuscitation. Functional capillary density and erythrocyte velocity in the mucosa and muscularis were determined by intravital microscopy. Leukocyte-endothelium interaction was studied in postcapillary venules and sympathetic nerve fibers of the intestinal wall were identified by immunohistochemistry.

Results
During hypotension functional capillary density was significantly (P < 0.001) lower in the muscularis of the control group (median [25/75 percentile]: -46.5% [-59.6/-20.8%] change from baseline) as compared with animals that received thoracic epidural anesthesia (-6.1% [-13.4/1.1%]). There were no differences in erythrocyte velocity between groups throughout the experiment. Leukocyte rolling increased significantly (P < 0.001) after resuscitation in control (12 [6/15] vs. baseline 2.5 [1/8]) but not in thoracic epidural anesthesia (4 [2.3/7] vs. baseline: 5 [3/15.5]). Sympathetic nerve fibers were identified in the muscularis and submucosa but not in the mucosa.

Conclusions
During hemorrhagic hypotension and after resuscitation, thoracic epidural anesthesia has beneficial effects on intestinal microvascular perfusion. Because of blockade of sympathetic nerves, thoracic epidural anesthesia prevents perfusion impairment of the muscularis during hypotension and attenuates leukocyte rolling after resuscitation.
Analgesic Efficacy of Inhaled Morphine in Patients after Bunionectomy Surgery
Authors: Thipphawong John B. , Babul Najib , Morishige Richard J. , Findlay Hugh K. , Reber Keith R. , Millward Gary J. , Otulana Babatunde A. 
Published: November 2003

Background
The AERx Pain Management System (Aradigm Corporation, Hayward, CA) is a novel pulmonary delivery system for the systemic administration of morphine. The authors compared the relative analgesic efficacy and safety of the AERx Pain Management System with those of placebo and intravenous morphine in an orthopedic postsurgical pain model.

Methods
Eighty-nine male and female PS-1 to PS-3 patients underwent standardized bunionectomy surgery and received multiple doses of inhaled or intravenous placebo, inhaled morphine (one inhalation [2.2 mg] or three inhalations [6.6 mg]), or intravenous morphine (4 mg) in a blinded fashion. Open-label rescue morphine (2 mg) was also available as needed. Pain intensity, pain relief, and time to pain relief were measured after the first dose. Global evaluation, morphine consumption, vital signs, and adverse events were monitored for 8 h after treatment. Blinded study personnel performed all treatment administrations and pain assessments.

Results
Three inhalations of morphine and 4 mg intravenous morphine provided comparable single- and multiple-dose analgesia. One inhalation of morphine was statistically indistinguishable from placebo. Three inhalations of morphine and 4 mg intravenous morphine both consistently demonstrated significantly greater analgesic efficacy than did placebo and one inhalation of morphine.

Conclusions
Comparable analgesic efficacy was demonstrated between a carefully matched dose of inhaled and intravenous morphine in a postsurgical pain model.
Effect of Auditory Evoked Potential Index Monitoring on Anesthetic Drug Requirements and Recovery Profile after Laparoscopic Surgery
Authors: Recart Alejandro , White Paul F. , Wang Agnes , Gasanova Irina , Byerly Stephanie , Jones Stephanie B. 
Published: November 2003

Background
The auditory evoked potential (AEP) monitor provides an electroencephalogram-derived index (AAI) that has been reported to correlate with the central nervous system depressant effects of anesthetic drugs. This clinical utility study was designed to test the hypothesis that AAI-guided administration of the maintenance anesthetics and analgesics would improve their titration and thereby provide a faster recovery from general anesthesia.

Methods
Seventy consenting patients undergoing elective general surgery procedures were randomly assigned to either a control (standard clinical practice) or AEP-monitored group. Although the AEP monitor was connected to all patients, the information from the monitor was only made available to the anesthesiologists assigned to patients in the AEP-monitored group. In the AEP-monitored group, the inspired desflurane concentration was titrated to maintain an AAI value of 15-20. In the control group, the inspired desflurane concentration was varied based on standard clinical signs. The AAI values and hemodynamic variables, as well as end-tidal desflurane concentrations, were recorded at 3- to 5-min intervals. The recovery times to achieve a White fast-track score greater than 12 and an Aldrete score of 10, as well as the actual duration of the PACU stay, were evaluated at 5- to 10-min intervals. Patient satisfaction with recovery from anesthesia was assessed using a 100-point verbal rating scale at 24 h after surgery.

Results
The average intraoperative AAI value in the AEP-monitored group was significantly higher than in the control group (16 +/- 5 vs. 11 +/- 8, P < 0.05). Use of the AEP monitor reduced the desflurane requirement by 26% compared to the control group (P < 0.01). In addition, the AEP-monitored group received less intraoperative fentanyl (270 +/- 120 vs. 390 +/- 203 microg, P < 0.05) and more rapidly achieved fast-track eligibility (29 +/- 19 vs. 56 +/- 41 min, P < 0.05). The time required to achieve an Aldrete score of 10 (60 +/- 31 vs. 98 +/- 55 min) and the duration of stay in the recovery room (78 +/- 32 vs. 106 +/- 54 min) were also significantly reduced in the AEP-monitored (vs. control) group (P < 0.05).

Conclusion
Use of AEP monitoring as an adjunct to standard clinical monitors improved titration of anesthetic drugs, thereby facilitating the early recovery process after laparoscopic surgery.
Sevoflurane Provides Greater Protection of the Myocardium than Propofol in Patients Undergoing Off-pump Coronary Artery Bypass Surgery
Authors: Conzen Peter F. , Fischer Susanne , Detter Christian , Peter Klaus 
Published: November 2003

Background
Sevoflurane, like other halogenated anesthetics, has been shown to have a protective effect on the myocardium at risk after an ischemic injury. The current study tested the hypothesis that such beneficial effects, so far mainly seen in the laboratory, are reproducible in humans.

Methods
After institutional review board approval, 20 patients scheduled to undergo elective off-pump coronary artery bypass surgery were randomized to receive general anesthesia with either sevoflurane or propofol. Except for this, anesthetic and surgical management was the same in both groups. For assessing myocardial injury, troponin I and myocardial fraction of creatine kinase were determined during the first 24 postoperative hours. Systemic hemodynamic variables were measured before, during, and after completion of coronary artery bypass.

Results
Troponin I concentrations increased significantly more in propofol-anesthetized patients than in patients anesthetized with sevoflurane.

Conclusion
Patients receiving sevoflurane for off-pump coronary artery surgery had less myocardial injury during the first 24 postoperative hours than patients receiving propofol. The results further support cardioprotective effects of sevoflurane.
Total Oxygen Uptake with Two Maximal Breathing Techniques and the Tidal Volume Breathing Technique
Authors: Pandit Jaideep J. , Duncan Thomas , Robbins Peter A. 
Published: November 2003

Background
Three common methods for preoxygenation are 3 min of tidal breathing, four deep breaths taken within 30 s (4DB), and eight deep breaths taken within 60 s (8DB). This report compares these three techniques in healthy volunteers.

Methods
Five healthy subjects breathed through a mouthpiece and wore a nose clip; oxygen was delivered at 180 l/min via a low-resistance T-piece. Each subject repeated each of the three oxygenation techniques four times. The end-tidal fraction of oxygen was measured, and the oxygen uptake at the mouth was measured breath by breath. The additional difference between oxygen uptake at the mouth during the period of breathing oxygen (as compared with that during air breathing) was taken to represent the total oxygen sequestrated into body stores.

Results
The mean +/- SD maximum end-tidal fraction of oxygen after the 4DB method was 0.83 +/- 0.09, which was significantly less than either after the 3-min method (0.92 +/- 0.01; P < 0.04) or after the 8DB method (0.91 +/- 0.04; P < 0.03). The mean additional oxygen taken up during oxygenation with the 4DB method was 1.67 +/- 0.45 l, which was significantly lower than with the 3-min method (2.23 +/- 0.85 l; P < 0.04) or with the 8DB method (2.53 +/- 0.74 l; P < 0.01). There were no significant differences for these variables between the 3-min and 8DB methods.

Conclusions
For the physiologic measurements that were made, both the 3-min and the 8DB method are superior to the 4DB method. The 3-min and 8DB methods seem to be equally effective.
Activation of α2B-Adrenoceptors Mediates the Cardiovascular Effects of Etomidate
Authors: Paris Andrea , Philipp Melanie , Tonner Peter H. , Steinfath Markus , Lohse Martin , Scholz Jens , Hein Lutz 
Published: November 2003

Background
The intravenous anesthetic etomidate exhibits structural similarities to specific alpha2-adrenoceptor agonists of the type such as dexmedetomidine. The current study was performed to elucidate the possible interaction of etomidate with alpha2-adrenoceptors in mice lacking individual alpha2-adrenoceptor subtypes (alpha2-KO).

Methods
Sedative and cardiovascular responses to etomidate and the alpha2-agonist, dexmedetomidine, were determined in mice deficient in alpha2-receptor subtypes. Inhibition of binding of the alpha2-receptor antagonist [3H]RX821002 to recombinant alpha2-receptors by etomidate was tested in human embryonic kidney (HEK293) cells in vitro.

Results
In vivo, loss and recovery of the righting reflex required similar times after intraperitoneal injection of etomidate in wild-type and in alpha2A-receptor-deficient mice, indicating that the hypnotic effect of etomidate in mice does not require the alpha2A-receptor subtype. Intravenous injection of etomidate resulted in a transient increase (duration 2.4 +/- 0.2 min) in arterial blood pressure in wild-type mice (17 +/- 3 mmHg). Etomidate did not affect blood pressure in alpha2B-KO or alpha2AB-KO mice. In membranes from HEK293 cells transfected with alpha2-receptors, etomidate inhibited binding of the alpha2-antagonist, [3H]RX821002, with higher potency from alpha2B- and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm). In alpha2B-receptor-expressing HEK293 cells, etomidate rapidly increased phosphorylation of the extracellular signal-related kinases ERK1/2.

Conclusions
These results indicate that etomidate acts as an agonist at alpha2-adrenoceptors, which appears in vivo primarily as an alpha2B-receptor-mediated increase in blood pressure. This effect of etomidate may contribute to the cardiovascular stability of patients after induction of anesthesia with etomidate.
Effects of Antidepressants on G Protein–coupled Receptor Signaling and Viability in Xenopus laevis Oocytes
Authors: Strümper Danja , Durieux Marcel E. , Tröster Barbara , Hahnenkamp Klaus , Vitan Cristina , den Bakker Christel G. , Hollmann Markus W. 
Published: November 2003

Background
Tricyclic antidepressants are structurally related to local anesthetics, suggesting that part of their analgesic action may result from properties shared with local anesthetics. Because local anesthetics block G protein-coupled receptor signaling (which explains, in part, their inflammatory modulating properties), the authors studied whether antidepressants have similar effects.

Methods
Peak Ca-activated Cl currents induced in Xenopus laevis oocytes by lysophosphatidic acid (10(-4) m) were measured using a voltage clamp. The effects of a 30-, 120-, or 240-min incubation in amitriptyline, nortriptyline, imipramine, or fluoxetine were determined.

Results
After a 30-min incubation, low concentrations (10(-7)-10(-5) m) of antidepressants had no effect on lysophosphatidic acid-induced currents. After prolonged incubation, only amitriptyline or nortriptyline inhibited lysophosphatidic acid signaling (each to 58% of the control response at 10(-7) m after 240 min). At low concentrations, none of the compounds induced membrane damage (defined as a holding current of > 1 microA, 2% in control cells). Imipramine at 10(-3) m induced damage in 100% of oocytes, and fluoxetine at 10(-4) m induced damage in 71% of oocytes (P < 0.05 vs. control). Amitriptyline and nortriptyline had no effect.

Conclusions
These findings are in part different from those obtained with local anesthetics and suggest that interference with G protein-coupled signaling might explain, in part, the analgesic properties of some antidepressants. However, use of antidepressants in high concentrations may be associated with cellular toxicity.
Brain Stem Opioidergic and GABAergic Neurons Mediate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats
Authors: Ohashi Yoko , Guo Tianzhi , Orii Ryo , Maze Mervyn , Fujinaga Masahiko 
Published: November 2003

Background
Recent studies have revealed that N2O exerts its antinociceptive effect by inducing opioid peptide release in the brain stem, thereby activating the descending noradrenergic inhibitory neurons, which modulate pain processing in the spinal cord. However, the precise neuronal pathways that mediate these events remain to be determined.

Methods
Using immunohistochemical and behavioral techniques in adult male Fischer rats, the authors studied the involvement of brain stem opioidergic and gamma-aminobutyric acid-mediated (GABAergic) neurons in the N2O-induced antinociceptive effect using discrete microinjections of an opioid receptor antagonist or GABAergic activator into the periaqueductal gray area and pontine noradrenergic nuclei. They used c-Fos expression as an immunohistochemical mark of neuronal activation induced by N2O and the plantar test as the behavioral paradigm for nociception.

Results
Microinjection of either naloxone (an opioid receptor antagonist) or muscimol (a gamma-aminobutyric acid receptor type A agonist) into the ventrolateral periaqueductal gray area inhibited N2O-induced c-Fos expression in the spinal cord and pontine noradrenergic nuclei, particularly in the A7. Microinjection of either naloxone or muscimol into the A7 nuclei also inhibited N2O-induced c-Fos expression in the spinal cord and the N2O-induced antinociceptive effect by the plantar test.

Conclusions
These results support the hypothesis that both opioidergic and GABAergic neurons mediate the antinociceptive effect of N2O at the periaqueductal gray area and A7 in the brain stem. The authors postulate that N2O-induced opioid peptide release leads to inhibition of GABAergic neurons via opioid receptors. The descending noradrenergic inhibitory pathways, which are tonically inhibited by these gamma-aminobutyric acid neurons, are thereby activated (disinhibited) and modulate pain processing in the spinal cord.
Synergistic Antinociceptive Effects of Ketamine and Morphine in the Orofacial Capsaicin Test in the Rat
Authors: Alvarez Pedro , Saavedra Gloria , Hernández Alejandro , Paeile Carlos , Pelissier Teresa 
Published: November 2003

Background
The clinical efficacy of the noncompetitive N-methyl-d-aspartate receptor antagonist ketamine for treating orofacial pain has already been reported. Side effects related to psychotomimetic disturbances, however, limit ketamine use as an analgesic. Theoretically, this limitation could be minimized by using low doses of ketamine in combination with other analgesics. In the present study, the potential synergistic antinociceptive interaction between ketamine and morphine in the orofacial capsaicin test in rats was investigated.

Methods
Male Sprague-Dawley rats were subcutaneously injected with solvent, ketamine, morphine, or combination of both drugs. Thirty minutes later, the orofacial capsaicin test was performed by injecting of 1.5 microg/25 microl of a capsaicin solution into the vibrissa pad. Animal behavior was recorded on videotape and analyzed off-line. The total time spent on rubbing-scratching nociceptive behavior during a period of 42 min was measured.

Results
Subcutaneously administered ketamine (0.4, 1.25, 4, 12.5 mg/kg), morphine (0.5, 1, 2, 4 mg/kg) and ketamine + morphine (0.20 + 0.12, 0.40 + 0.24, 0.80 + 0.49, 1.61 + 0.97, 3.21 + 1.94 mg/kg) reduced the rat facial rubbing-scratching behavior in a dose-dependent manner. Isobolographic analysis showed that the ketamine + morphine association inhibited the studied behavior in a superadditive manner.

Conclusions
These results indicate that ketamine and morphine have antinociceptive effects on the orofacial capsaicin test. Furthermore, their combination produces synergistic antinociception. It is therefore suggested that, used together, ketamine and morphine might be clinically efficient at lower doses than those currently used when administered separately. This could provide a useful strategy for the clinical management of orofacial pain.