bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Lidocaine on Endotoxin-induced Leukocyte-Endothelial Cell Adhesion and Macromolecular Leakage in Vivo
Authors: Schmidt Werner , Schmidt Heinfried , Bauer Harald , Gebhard Martha Maria , Martin Eike 
Published: November 2003

Background
Endotoxin activates leukocyte-endothelial cell adhesion, vascular leakage, and changes in vascular micro-hemodynamics. The aim of this study was to determine whether lidocaine, which inhibits the activation of leukocytes, could attenuate microcirculatory disturbances during endotoxemia.

Methods
Thirty anesthetized male rats were randomly assigned to receive one of three treatments (n = 10 for each group): infusion of saline (control group), infusion of Escherichia coli endotoxin (LPS group: 2 mg x kg(-1) x h(-1) lipopolysaccharides) without lidocaine treatment, or infusion of endotoxin with lidocaine pretreatment 30 min before baseline measurements (lidocaine group: intravenous bolus of 2 mg/kg and continuous infusion of 2 mg x kg(-1) x h(-1)). Leukocyte adherence, erythrocyte velocity (V(RBC), and vessel diameters (Dv) were determined at baseline and at 60 and 120 min in mesenteric postcapillary venules using in vivo videomicroscopy. Macromolecular leakage was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wall shear rate (tau) was calculated according to the equation tau = 8 x V(RBC) x Dv(-1).

Results
Lidocaine significantly attenuated the increase of leukocyte adherence during endotoxemia. There were no significant differences of tau within or between the groups. Macromolecular leakage exhibited the greatest increase in the LPS group. In the lidocaine group, it was significantly decreased but still increased compared with the control group.

Conclusions
These results show that lidocaine attenuates endotoxin-induced alterations in leukocyte-endothelial cell adhesion and macromolecular leakage, which suggests that lidocaine may have a therapeutic role in preventing endothelial damage in sepsis.
Halothane Attenuates Endothelium-dependent Pulmonary Vasorelaxant Response to Lemakalim, an Adenosine Triphosphate (ATP)-sensitive Potassium Channel Agonist
Authors: Seki Sumihiko , Horibe Mayumi , Murray Paul A. 
Published: November 2003

Background
Lemakalim, an adenosine triphosphate (ATP)-sensitive potassium (K+(ATP)) channel agonist, causes profound pulmonary vasodilation in conscious dogs, which is attenuated during halothane anesthesia. The goal of the present study was to investigate the mechanism responsible for this attenuating effect of halothane.

Methods
Isolated canine pulmonary arterial rings were suspended for isometric tension recording in 25 ml organ baths. Rings with and without endothelium were contracted to 50% of their maximal response to phenylephrine, followed by the cumulative administration of lemakalim with or without exposure to halothane (0.5-1.5 minimum alveolar concentration [MAC] in dogs). Lemakalim dose-response curves were also generated in rings pretreated with the nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME); the cyclooxygenase inhibitor, indomethacin; or the K+(ATP) channel antagonist, glybenclamide.

Results
Compared with intact rings, the pulmonary vasorelaxant response to lemakalim was attenuated (P < 0.05) in endothelium-denuded rings. Halothane at 0.5 MAC had no effect on the vasorelaxant response to lemakalim. Halothane at 1 MAC attenuated (P < 0.05) the vasorelaxant response to lemakalim in intact rings, but not in endothelium-denuded rings. Halothane at 1.5 MAC attenuated (P < 0.05) the vasorelaxant response to lemakalim in both intact and endothelium-denuded rings. In endothelium-intact rings, indomethacin attenuated (P < 0.05) the vasorelaxant response to lemakalim, whereas L-NAME had no effect. Further, indomethacin, but not L-NAME, abolished the endothelium-dependent, halothane-induced attenuation of the lemakalim vasorelaxation response. Glybenclamide markedly attenuated (P < 0.05) lemakalim vasorelaxation at lemakalim doses less than 10(-6) M.

Conclusions
Lemakalim-induced pulmonary vasorelaxation involves an endothelium-dependent and vascular smooth muscle component. Further, halothane attenuates the endothelium-dependent pulmonary vasorelaxant response to lemakalim via an inhibitory effect on vasodilator metabolites of the cyclooxygenase pathway.
Nitric Oxide Produced by Inducible Nitric Oxide Synthase Delays Gastric Emptying in Lipopolysaccharide-treated Rats
Authors: Takakura Ko , Hasegawa Koichi , Goto Yukio , Muramatsu Ikunobu 
Published: November 2003

Background
Endotoxin induces nitric oxide synthase (NOS), resulting in relaxation of gastric smooth muscle. The authors examined the effect of NO produced in response to lipopolysaccharide (LPS) treatment on gastric emptying in rats, and they also examined the effects of a selective inhibitor of inducible NOS (iNOS), aminoguanidine, and a suppressor of iNOS gene expression, dexamethasone.

Methods
Male Wistar rats weighing 200-250 g were used. LPS-treated rats received LPS (0.2-10 mg/kg) diluted in physiologic saline intraperitoneally. Before and at different intervals up to 8 h after administration of LPS, measurements of gastric emptying were performed in groups of 3-5 rats, by determining the amount of phenol red remaining in the stomach 20 min after intragastric instillation. In additional group of LPS (2 mg/kg)-treated rats, the gastric fundus was isolated 6 h after administration, and the tension changes in response to L-arginine, a substrate for NOS, and electrical transmural stimulation (3 Hz, 5 s) were recorded isometrically.

Results
(1) Gastric emptying was delayed by pretreatment with LPS in a dose- and time-dependent fashion (reduction from 68 +/- 12% to 22 +/- 7% with a dose of 2 mg/kg for 6 h). Aminoguanidine (50 mg/kg) or dexamethasone (5 mg/kg) partially inhibited the delay (to 39 +/- 4% or to 40 +/- 10%, respectively). (2) L-arginine (0.1 mM) produced a relaxation (28 +/- 2% reduction in active tension) in the gastric fundus strips isolated from LPS-treated rats but not from LPS-untreated rats. The relaxation was inhibited by aminoguanidine (1 mM). In contrast, the relaxation response to the electrical stimulation was not affected by aminoguanidine (0.1-1 mM).

Conclusion
The present study suggests that NO, probably produced by iNOS, is one of the factors involved in the delay of gastric emptying in the LPS-treated rats and probably in those with sepsis.
Adverse Anesthetic Outcomes Arising from Gas Delivery Equipment
Authors: Caplan Robert A. , Vistica Mary F. , Posner Karen L. , Cheney Frederick W. 
Published: November 2003

Background
Anesthesia gas delivery equipment is a potentially important source of patient injury. To better define the contribution of gas delivery equipment to professional liability in anesthesia, the authors conducted an in-depth analysis of cases from the database of the American Society of Anesthesiologists Closed Claims Project.

Methods
The database of the Closed Claims Project is composed of closed US malpractice claims that have been collected in a standardized manner. All claims resulting from the use of gas delivery equipment were reviewed for recurrent patterns of injury.

Results
Gas delivery equipment was associated with 72 (2%) of 3,791 claims in the database. Death and permanent brain damage accounted for almost all adverse outcomes (n = 55, 76%). Equipment misuse was defined as fault or human error associated with the preparation, maintenance, or deployment of a medical device. Equipment failure was defined as unexpected malfunction of a medical device, despite routine maintenance and previous uneventful use. Misuse of equipment (n = 54, 75%) was three times more common than equipment failure (n = 17, 24%). Misconnects and disconnects of the breathing circuit made the largest contribution to injury (n = 25, 35%). Reviewers judged that 38 of 72 claims (53%) could have been prevented by pulse oximetry, capnography, or a combination of these two monitors. Overall, 56 of 72 gas delivery claims (78%) were deemed preventable with the use or better use of monitors. The year of occurrence for claims involving gas delivery equipment ranged from 1962 to 1991 and did not differ significantly from claims involving other adverse respiratory events.

Conclusions
Claims associated with gas delivery equipment are infrequent but severe and continue to occur in the 1990s. Educational and preventive strategies that focus on equipment misuse and breathing circuit configuration may have the greatest potential for enhancing the safety of anesthesia gas delivery equipment.
The Comparative Amnestic Effects of Midazolam, Propofol, Thiopental, and Fentanyl at Equisedative Concentrations
Authors: Veselis Robert A. , Reinsel Ruth A. , Feshchenko Vladimir A. , Wronski Marek 
Published: November 2003

Background
The authors evaluated the effects of midazolam, propofol, thiopental, and fentanyl on volunteer participants' memory for words and pictures at equisedative concentrations.

Methods
Sixty-seven healthy volunteers were randomized to receive intravenous infusions of midazolam (n = 11), propofol (n = 11), thiopental (n = 10), fentanyl with ondansetron pretreatment (n = 11), ondansetron alone (n = 8), or placebo (n = 16) in a double-blind design. Three increasing and then two decreasing sedative concentrations were achieved by computer-controlled infusion in each volunteer. Measures of sedation, memory, and drug concentration were obtained at each target concentration. Drug concentrations were normalized to equisedative effects using both Emax and logistic regression methods of pharmacodynamic modeling. The serum concentrations at 50% memory effect (Cp50s) were determined using four different memory end points. The relative potencies compared with midazolam for memory impairment were determined.

Results
Equisedative concentrations were midazolam, 64.5 +/- 9.4 ng/ml; propofol, 0.7 +/- 0.2 microg/ml; thiopental, 2.9 /- 1.0 microg/ml; and fentanyl, 0.9 +/- 0.2 ng/ml. The Cp50s for 50% loss of memory for words were midazolam, 56 +/- 4 ng/ml; propofol, 0.62 +/- 0.04 microg/ml; thiopental, 4.5 +/- 0.3 microg/ml; and fentanyl, 3.2 +/- 0.4 ng/ml. Compared with midazolam, relative potencies (with 95% confidence intervals) were propofol, 0.96 (0.44-1.78); thiopental, 0.76 (0.52-0.94); and fentanyl, 0.34 (0.05-0.76). Large effects on memory were only produced by propofol and midazolam.

Conclusions
At equal sedation, propofol produces the same degree of memory impairment as midazolam. Thiopental has mild memory effects whereas fentanyl has none. Ondansetron alone has no sedative or amnesic effects.
Computer Simulation of the Effects of Alterations in Blood Flows and Body Composition on Thiopental Pharmacokinetics in Humans
Authors: Wada D. Russell , Bjorkman Sven , Ebling William F. , Harashima Hideyoshi , Harapat Sandra R. , Stanski Donald R. 
Published: November 2003

Background
Understanding the influence of physiological variables on thiopental pharmacokinetics would enhance the scientific basis for the clinical usage of this anesthetic.

Methods
A physiological pharmacokinetic model for thiopental previously developed in rats was scaled to humans by substituting human values for tissue blood flows, tissue masses, and elimination clearance in place of respective rat values. The model was validated with published serum concentration data from 64 subjects. The model was simulated after intravenous thiopental administration, 250 mg, over 1 min, to predict arterial plasma concentrations under conditions of different cardiac outputs, degrees of obesity, gender, or age.

Results
The human pharmacokinetic model is characterized by a steady state volume of distribution of 2.2 l/kg, an elimination clearance of 0.22 l/min, and a terminal half-life of 9 h. Measured thiopental concentrations are predicted with an accuracy of 6 +/- 37% (SD). Greater peak arterial concentrations are predicted in subjects with a low versus a high cardiac output (3.1 and 9.4 l/min), and in subjects who are lean versus obese (56 and 135 kg). Acutely, obesity influences concentrations because it affects cardiac output. Prolonged changes are due to differences in fat mass. Changes with gender and age are relatively minor.

Conclusions
The physiological pharmacokinetic model developed in rats predicts thiopental pharmacokinetics in humans. Differences in basal cardiac output may explain much of the variability in early thiopental disposition between subjects.
Halothane and Xanthine Oxidase Increase Hepatocellular Enzyme Release and Circulating Lactate after Ischemia-Reperfusion in Rabbits
Authors: Nielsen Vance G. , Tan Sidhartha , Kirk Katharine A. , Baird Manuel S. , McCammon Andrew T. , Samuelson Paul N. , Parks Dale A. 
Published: November 2003

Background
Multiple-organ injury often occurs after aortic occlusion-reperfusion. Oxidants derived from xanthine oxidase have been implicated as a source of injury after aortic occlusion-reperfusion. Halogenated anesthetics modify oxidant-mediated injury. The current study determined if halothane modifies hepatocellular enzyme release (e.g., alanine aminotransferase) and circulating lactate after aortic occlusion-reperfusion.

Methods
Rabbits were randomly assigned to one of four groups that underwent 40 min of thoracic aortic occlusion and 2 h of reperfusion: Two groups were given either halothane or fentanyl plus droperidol anesthesia and two groups were given either anesthetic and sodium tungstate (xanthine oxidase inactivator). Each of the four groups was then matched with a similarly treated group that did not undergo aortic occlusion.

Results
Halothane anesthesia was associated with significantly (P < 0.05) increased release of alanine aminotransferase (34 +/- 9 U/l at baseline and 539 +/- 370 U/l at 120 min of reperfusion; mean +/- SD) and increased plasma lactate concentrations (2.8 +/- 2.0 mM at baseline and 12.1 +/- 9.7 mM at 120 min of reperfusion) after aortic occlusion-reperfusion compared with fentanyl plus droperidol anesthesia (alanine aminotransferase, 33 +/- 12 U/l and 148 +/- 109 U/l; lactate, 3.4 +/- 2.0 mM and 3.8 +/- 1.2 mM at baseline and 120 min of reperfusion, respectively). Inactivation of xanthine oxidase significantly decreased the release of hepatocellular enzymes (P < 0.05) and decreased circulating lactate in animals anesthetized with halothane after aortic occlusion-reperfusion.

Conclusions
Halothane increased hepatocellular enzyme release and circulating lactate after aortic occlusion-reperfusion compared with fentanyl plus droperidol anesthesia. Xanthine oxidase activity inactivation also decreased hepatocellular enzyme activity release during reperfusion. These findings justify further investigations to determine if halogenated anesthetics modify tissue injury in clinical settings involving oxidant stress.
Transient Neuronal Depolarization Induces Tolerance to Subsequent Forebrain Ischemia in Rats
Authors: Taga Kiichiro , Patel Piyush M. , Drummond John C. , Cole Daniel J. , Kelly Paul J. 
Published: November 2003

Background
Minor cortical injury has previously been shown to improve survival in animals subjected to ischemic insults. Although the mechanism by which an ischemia-tolerant state is achieved is not clear, transient neuronal depolarization is thought to play a central role in the development of the tolerance. One way of producing transient neuronal depolarization is by the induction of cortical spreading depression (CSD). The present study was conducted to evaluate the effect of preischemic transient depolarization, induced by CSD, on postischemic neuronal outcome in rats.

Methods
Unilateral CSD was induced by application of KCl to the frontal cortex (CSD hemisphere) in three groups of isoflurane-anesthetized rats (CSD groups; n = 8/group). Sham animals (n = 12) did not undergo CSD. In a fifth group (n = 8), ketamine was administered during KCl application to inhibit CSD. One, three, or seven days after CSD, animals were subjected to forebrain ischemia produced by bilateral carotid artery occlusion. Injury to the striatum, hippocampus, and cortex was evaluated in hematoxylin and eosin-stained brain sections 3 days after ischemia.

Results
Preischemic CSD reduced postischemic injury in the ipsilateral cortex. The ratio of the number of injured neurons in the CSD hemisphere to that in the non-CSD hemisphere was significantly less in the groups subjected to CSD 1 day (0.51 +/- 0.33), 3 days (0.56 /- 0.22), and 7 days (0.40 +/- 0.17) before ischemia than in the sham operated group (1.11 +/- 0.47). In the ketamine group (CSD inhibition), there were no differences in the extent of injury in the two hemispheres (ratio = 0.84 +/- 0.47). Injury to the striatum and hippocampus was similar among the groups. Within each group, injury to these subcortical structures in the CSD hemisphere was not different from that in the non-CSD hemisphere.

Conclusions
The data suggest that preischemic depolarization induced by CSD results in an adaptive response that reduces the vulnerability of cortical neurons to subsequent ischemic injury (ischemic tolerance).
Functional Assessment of the Pharynx at Rest and during Swallowing in Partially Paralyzed Humans
Authors: Eriksson Lars I. , Sundman Eva , Olsson Rolf , Nilsson Lena , Witt Hanne , Ekberg Olle , Kuylenstierna Richard 
Published: November 2003

Background
Functional characteristics of the pharynx and upper esophagus, including aspiration episodes, were investigated in 14 awake volunteers during various levels of partial neuromuscular block. Pharyngeal function was evaluated using videoradiography and computerized pharyngeal manometry during contrast bolus swallowing.

Methods
Measurements of pharyngeal constrictor muscle function (contraction amplitude, duration, and slope), upper esophageal sphincter muscle resting tone, muscle coordination, bolus transit time, and aspiration under fluoroscopic control (laryngeal or tracheal penetration) were made before (control measurements) and during a vecuronium-induced partial neuromuscular paralysis, at fixed intervals of mechanical adductor pollicis muscle train-of-four (TOF) fade; that is, at TOF ratios of 0.60, 0.70, 0.80, and after recovery to a TOF ratio > 0.90.

Results
Six volunteers aspirated (laryngeal penetration) at a TOF ratio < 0.90. None of them aspirated at a TOF ratio > 0.90 or during control recording. Pharyngeal constrictor muscle function was not affected at any level of paralysis. The upper esophageal sphincter resting tone was significantly reduced at TOF ratios of 0.60, 0.70, and 0.80 (P < 0.05). This was associated with reduced muscle coordination and shortened bolus transit time at a TOF ratio of 0.60.

Conclusions
Vecuronium-induced partial paralysis cause pharyngeal dysfunction and increased risk for aspiration at mechanical adductor pollicis TOF ratios < 0.90. Pharyngeal function is not normalized until an adductor pollicis TOF ratio of > 0.90 is reached. The upper esophageal sphincter muscle is more sensitive to vecuronium than is the pharyngeal constrictor muscle.
Pharyngeal Patency in Response to Advancement of the Mandible in Obese Anesthetized Persons
Authors: Isono Shiroh , Tanaka Atsuko , Tagaito Yugo , Sho Yasuhide , Nishino Takashi 
Published: November 2003

Background
During anesthesia in humans, anterior displacement of the mandible is often helpful to relieve airway obstruction. However, it appears to be less useful in obese patients. The authors tested the possibility that obesity limits the effectiveness of the maneuver.

Methods
Total muscle paralysis was induced under general anesthesia in a group of obese persons (n = 9; body mass index, 32 +/- 3 kg[-2]) and in a group of nonobese persons (n = 9; body mas index, 21 +/- 2 kg[-2]). Nocturnal oximetry confirmed that none of them had sleep-disordered breathing. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. A static pressure-area plot allowed assessment of the mechanical properties of the pharynx. The influence of mandibular advancement on airway patency was assessed by comparing the static pressure-area relation with and without the maneuver in obese and nonobese persons.

Results
Mandibular advancement increased the retroglossal area at a given pharyngeal pressure, and mandibular advancement increased the retropalatal area in nonobese but not in obese persons at a given pharyngeal pressure.

Conclusion
Mandibular advancement did not improve the retropalatal airway in obese persons.
Regulation of Mu Opioid Receptor mRNA Levels by Activation of Protein Kinase C in Human SH-SY5Y Neuroblastoma Cells
Authors: Gies Elizabeth K. , Peters Dawn M. , Gelb Carol R. , Knag Kathleen M. , Peterfreund Robert A. 
Published: November 2003

Background
The mu opioid receptor (MuOR) is a member of the superfamily of G protein-coupled receptors that mediates the analgesic actions of endogenous opioid peptides and the narcotic alkaloid derivatives of morphine. Activation and translocation of protein kinase C (PKC) by N-methyl-D-aspartate receptor stimulation correlates with resistance to opioid drugs in experimental states of neuropathic pain, but the cellular mechanisms of resistance have not been identified. One possibility is that PKC activation regulates MuOR mRNA expression and thus the ability to generate functional receptors. Using a human neuroblastoma cell line, the authors tested the hypothesis that phorbol ester activation of PKC regulates MuOR mRNA levels.

Methods
SH-SY5Y cells were maintained in a continuous monolayer culture and treated with phorbol esters or other agents before extraction of total cellular RNA. Slot-blot hybridization was used to measure the level of MuOR mRNA using 32P-labeled MuOR cDNA probes under high-stringency conditions. Autoradiograms were analyzed by scanning and densitometry.

Results
MuOR mRNA levels decreased in a dose- and time-dependent manner after tetradecanoyl phorbol acetate (TPA) was administered to activate PKC. The nadir, a level of approximately 50% of control, was at 2-8 h, followed by gradual recovery. The actions of TPA were blocked by pretreatment with the selective PKC inhibitor bisindolylmaleimide, but not by inhibition of protein synthesis with cycloheximide or anisomycin. The combination of TPA treatment and transcription inhibition with actinomycin D was associated with a transient increase in MuOR mRNA.

Conclusions
Mu opioid receptor mRNA levels are regulated by activation of PKC in a neuronal model. Protein kinase C effects which decrease MuOR mRNA levels appear largely independent of new protein synthesis, and cytotoxicity does not account for the findings. Plasticity of MuOR gene expression may contribute to variations in clinical responses to opioid analgesics in clinical states such as neuropathic pain.