bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the Rostral Medial Medulla in the Development of Primary and Secondary Hyperalgesia after Incision in the Rat
Authors: Bosnjak Zeljko J. , Pogatzki Esther M. , Urban Mark O. , Brennan Timothy J. , Gebhart Gerald F. 
Published: November 2003

Background
Descending influences from the rostral medial medulla (RMM) contribute to secondary hyperalgesia in persistent inflammatory, neuropathic, and visceral pain models. The current study examined if descending inhibition or facilitation from the RMM modulates primary and secondary hyperalgesia after incision in the rat hind limb.

Methods
Bilateral RMM lesions were produced using the soma-selective neurotoxin ibotenic acid, and the effect of RMM lesion was examined on primary and secondary hyperalgesia 5 days after a plantar or gastrocnemius incision, respectively.

Results
Plantar incision reduced withdrawal thresholds to von Frey filaments applied adjacent to the incision (primary punctate hyperalgesia). The withdrawal thresholds were the same in RMM-lesioned and sham-operated rats. The response frequency to a blunt mechanical stimulus after plantar incision was increased (primary nonpunctate hyperalgesia) in both groups. Nonpunctate hyperalgesia was greater in lesioned rats on postoperative day 2 only; all other measures were not different. Primary heat hyperalgesia after plantar incision was not modulated by RMM lesion. Secondary punctate hyperalgesia after gastrocnemius incision was not affected by RMM lesion. Gastrocnemius incision did not produce secondary nonpunctate or heat hyperalgesia in either RMM lesion or sham rats.

Conclusion
Primary and secondary hyperalgesia after an incision were not modulated by descending influence from the RMM. The lack of contribution of descending facilitatory influences from the RMM to secondary hyperalgesia after gastrocnemius incision supports the notion that incision-induced pain involves dissimilar mechanisms compared with inflammatory and neuropathic pain.
Thiopental Inhibits the Activation of Nuclear Factor κB
Authors: Loop Torsten , Liu Zhiheng , Humar Matjaz , Hoetzel Alexander , Benzing Albert , Pahl Heike L. , Geiger Klaus K. , J. Pannen Benedikt H. 
Published: November 2003

Background
Thiopental is frequently used for the treatment of intracranial hypertension after severe head injury. Its long-term administration increases the incidence of nosocomial infections, which contributes to the high mortality rate of these patients. However, the mechanism of its immunosuppressing effect remains unknown.

Methods
The effect of thiopental (200-1000 microg/ml) on the activation of the nuclear transcription factor kappaB (NF-kappaB; electrophoretic mobility shift assays), on NF-kappaB-driven reporter gene activity (transient transfection assays), on the expression of NF-kappaB target genes (enzyme-linked immunoassays), on T-cell activation (flow cytometric analyses of CD69 expression), and on the content of the NF-kappaB inhibitor IkappaB-alpha (Western blotting) was studied in human T lymphocytes in vitro.

Results
Thiopental inhibited the activation of the transcription factor NF-kappaB but did not alter the activity of the cyclic adenosine monophosphate response element binding protein. Other barbiturates (methohexital), anesthetics (etomidate, propofol, ketamine), or opioids (fentanyl, morphine) did not affect NF-kappaB activation. Thiopental-mediated suppression of NF-kappaB could be observed in Jurkat cells and in primary CD3+ lymphocytes from healthy volunteers, was time- and concentration-dependent, occurred at concentrations that are clinically achieved, and persisted for hours after the incubation. It was associated with an inhibition of NF-kappaB-driven reporter gene activity, of the expression of interleukin-2, -6, and -8, and interferon gamma, and of the activation of CD3+ lymphocytes. Suppression of NF-kappaB appeared to involve reduced degradation of IkappaB-alpha.

Conclusion
The results demonstrate that thiopental inhibits the activation of NF-kappaB and may thus provide a molecular mechanism for some of the immunosuppressing effects associated with thiopental therapy.
Comparison of Electrophysiologic Effects of Propofol and Isoflurane-based Anesthetics in Children Undergoing Radiofrequency Catheter Ablation for Supraventricular Tachycardia
Authors: Erb Thomas O. , Kanter Ronald J. , Hall Janet M. , Gan Tong J. , Kern Frank H. , Schulman Scott R. 
Published: November 2003

Background
Radiofrequency catheter ablation (RFCA), which is typically performed with general anesthesia in children, is an interventional therapy for tachyarrhythmia. Although the electrophysiologic (EP) effects of isoflurane- and propofol-based anesthetics have been shown to be similar, a retrospective analysis reported significantly longer RFCA procedural duration with the use of isoflurane. It remains unclear whether the ability to successfully perform RFCA differs between these drugs.

Methods
Patients were randomly assigned to receive either an isoflurane- or propofol-maintained anesthetic. Drug administration was titrated according to the pharmacodynamic endpoint of depth of sedation using bispectral index score. The ability to induce sustained tachycardia (using a scoring system), procedural durations, and effects on cardiac electrophysiologic properties were evaluated and compared between the groups.

Results
Sixty subjects were included in this study. Sustained supraventricular tachycardia (SVT) was inducible with the assigned drug in all but four subjects. In three of these four subjects, SVT was also not inducible with the alternative study drug. Ability to induce the first sustained SVT was similar between the groups (P = 0.83). Total procedural durations were similar (isoflurane 224 +/- 84 min vs. propofol 221 +/- 86 min, mean +/- SD, P = 0.88). Atrioventricular nodal conduction was slower with propofol compared with isoflurane, but this result did not appear to be clinically relevant. Finally, ventricular repolarization was prolonged by isoflurane versus propofol, the clinical significance of which was not demonstrated.

Conclusion
Isoflurane- and propofol-based anesthesia were equally suitable in children and adolescents undergoing RFCA.
Clinically Relevant Concentrations of Propofol Have No Effect on Adenosine Triphosphate–sensitive Potassium Channels in Rat Ventricular Myocytes
Authors: Kawano Takashi , Oshita Shuzo , Tsutsumi Yasuo , Tomiyama Yoshinobu , Kitahata Hiroshi , Kuroda Yasuhiro , Takahashi Akira , Nakaya Yutaka 
Published: November 2003

Background
Activation of adenosine triphosphate-sensitive potassium (K(ATP)) channels produces cardioprotective effects during ischemia. Because propofol is often used in patients who have coronary artery disease undergoing a wide variety of surgical procedures, it is important to evaluate the direct effects of propofol on K(ATP) channel activities in ventricular myocardium during ischemia.

Methods
The effects of propofol (0.4-60.1 microg/ml) on both sarcolemmal and mitochondrial K(ATP) channel activities were investigated in single, quiescent rat ventricular myocytes. Membrane currents were recorded using cell-attached and inside-out patch clamp configurations. Flavoprotein fluorescence was measured to evaluate mitochondrial oxidation mediated by mitochondrial K(ATP) channels.

Results
In the cell-attached configuration, open probability of K(ATP) channels was reduced by propofol in a concentration-dependent manner (EC(50) = 14.2 microg/ml). In the inside-out configurations, propofol inhibited K(ATP) channel activities without changing the single-channel conductance (EC(50) = 11.4 microg/ml). Propofol reduced mitochondrial oxidation in a concentration-dependent manner with an EC(50) of 14.6 microg/ml.

Conclusions
Propofol had no effect on the sarcolemmal K(ATP) channel activities in patch clamp configurations and the mitochondrial flavoprotein fluorescence induced by diazoxide at clinically relevant concentrations (< 2 microm), whereas it significantly inhibited both K(ATP) channel activities at very high, nonclinical concentrations (> 5.6 microg/ml; 31 microm).
Isoflurane Pretreatment Inhibits Cytokine-induced Cell Death in Cultured Rat Smooth Muscle Cells and Human Endothelial Cells
Authors: de Klaver Manuela J. M. , Manning Lee , Palmer Lisa A. , Rich George F. 
Published: November 2003

Background
Anesthetics are protective during ischemic-reperfusion injury and associated inflammation; therefore, the authors hypothesized that anesthetic pretreatment may provide protection in culture from cytokine-induced cell death.

Methods
Rat vascular smooth muscle (VSM) cell and human umbilical vascular endothelial cell (HUVEC) cultures were used to determine whether pretreatment with 30 min of isoflurane decreases cell death from tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1 beta), and interferon (IFN-gamma) alone or in combination. Cell survival and viability were determined by trypan blue staining and cell proliferation assay, as well as by DNA fragmentation assays. The roles of protein kinase C (PKC) and adenosine triphosphate-sensitive potassium (K(ATP)) channels in mediating isoflurane (and halothane) protection were evaluated with the antagonists staurosporine or glibenclamide in cytokine- and also hydrogen peroxide (H(2)O(2))-induced cell death.

Results
Pretreatment with 1.5% isoflurane immediately prior to cytokine exposure increased cell survival and viability from cytokines by 10-60% for 24, 48, 72, and 96 h in VSMs and up to 72 h in HUVECs. DNA fragmentation (TUNEL) was also attenuated by isoflurane. Isoflurane was equally effective in VSMs at 0.75, 1.5, and 2.5%, whereas in HUVECs, 1.5 and 2.5% were more effective than 0.75%. In VSMs, isoflurane administered 1 h prior to or simultaneously with cytokines was also effective, whereas isoflurane 2 h prior to cytokines was less effective, and either 4 h prior to or 30 min after cytokines was not effective. In both cytokine- and H(2)O(2)-induced cell death, isoflurane and halothane pretreatment were equally protective, and staurosporine and glibenclamide attenuated the protective effect.

Conclusions
Thirty minutes of isoflurane attenuates cytokine-induced cell death and increases cell viability in VSMs for 96 h and in HUVECs for 72 h. Isoflurane must be administered less than 2 h prior to or simultaneously with the cytokines to be protective. These initial inhibitor studies suggest involvement of PKC and K(ATP) channels in isoflurane and halothane protection against both cytokine- and H(2)O(2)-induced cell death of VSMs and HUVECs.
Differential Modulation of the Cardiac Adenosine Triphosphate-sensitive Potassium Channel by Isoflurane and Halothane
Authors: Kwok Wai-Meng , Martinelli Anne T. , Fujimoto Kazuhiro , Suzuki Akihiro , Stadnicka Anna , Bosnjak Zeljko J. 
Published: November 2003

Background
The cardiac adenosine triphosphate-sensitive potassium (K(ATP)) channel is activated during pathophysiological episodes such as ischemia and hypoxia and may lead to beneficial effects on cardiac function. Studies of volatile anesthetic interactions with the cardiac K(ATP) channel have been limited. The goal of this study was to investigate the ability of volatile anesthetics halothane and isoflurane to modulate the cardiac sarcolemmal K(ATP) channel.

Methods
The K(ATP) channel current (I(KATP)) was monitored using the whole cell configuration of the patch clamp technique from single ventricular cardiac myocytes enzymatically isolated from guinea pig hearts. I(KATP) was elicited by extracellular application of the potassium channel openers 2,4-dinitrophenol or pinacidil.

Results
Volatile anesthetics modulated I(KATP) in an anesthetic-dependent manner. Isoflurane facilitated the opening of the K(ATP) channel. Following initial activation of I(KATP) by 2,4-dinitrophenol, isoflurane at 0.5 and 1.3 mm further increased current amplitude by 40.4 +/- 11.1% and 58.4 +/- 20.6%, respectively. Similar results of isoflurane were obtained when pinacidil was used to activate I(KATP). However, isoflurane alone was unable to elicit K(ATP) channel opening. In contrast, halothane inhibited I(KATP) elicited by 2,4-dinitrophenol by 50.6 +/- 5.8% and 72.1 +/- 11.6% at 0.4 and 1.0 mm, respectively. When I(KATP) was activated by pinacidil, halothane had no significant effect on the current.

Conclusions
The cardiac sarcolemmal K(ATP) channel is differentially modulated by volatile anesthetics. Isoflurane can facilitate the further opening of the K(ATP) channel following initial channel activation by 2,4-dinitrophenol or pinacidil. The effect of halothane was dependent on the method of channel activation, inhibiting I(KATP) activated by 2,4-dinitrophenol but not by pinacidil.
Anesthestic-related Cardiac Arrest and Its Mortality
Authors: Newland Myrna C. , Ellis Sheila J. , Lydiatt Carol A. , Peters K. Reed , Tinker John H. , Romberger Debra J. , Ullrich Fred A. , Anderson James R. 
Published: November 2003

Background
A prospective and retrospective case analysis study of all perioperative cardiac arrests occurring during a 10-yr period from 1989 to 1999 was done to determine the incidence, cause, and outcome of cardiac arrests attributable to anesthesia.

Methods
One hundred forty-four cases of cardiac arrest within 24 h of surgery were identified over a 10-yr period from an anesthesia database of 72,959 anesthetics. Case abstracts were reviewed by a Study Commission composed of external and internal members in order to judge which cardiac arrests were anesthesia-attributable and which were anesthesia-contributory. The rates of anesthesia-attributable and anesthesia-contributory cardiac arrest were estimated.

Results
Fifteen cardiac arrests out of a total number of 144 were judged to be related to anesthesia. Five cardiac arrests were anesthesia-attributable, resulting in an anesthesia-attributable cardiac arrest rate of 0.69 per 10,000 anesthetics (95% confidence interval, 0.085-1.29). Ten cardiac arrests were found to be anesthesia-contributory, resulting in an anesthesia-contributory rate of 1.37 per 10,000 anesthetics (95% confidence interval, 0.52-2.22). Causes of the cardiac arrests included medication-related events (40%), complications associated with central venous access (20%), problems in airway management (20%), unknown or possible vagal reaction in (13%), and one perioperative myocardial infarction. The risk of death related to anesthesia-attributable perioperative cardiac arrest was 0.55 per 10,000 anesthetics (95% confidence interval, 0.011-1.09).

Conclusions
Most perioperative cardiac arrests were related to medication administration, airway management, and technical problems of central venous access. Improvements focused on these three areas may result in better outcomes.
Impact of Unplanned Extubation and Reintubation after Weaning on Nosocomial Pneumonia Risk in the Intensive Care Unit
Authors: de Lassence Arnaud , Alberti Corinne , Azoulay Élie , Le Miere Eric , Cheval Christine , Vincent François , Cohen Yves , Garrouste-Orgeas Maïté , Adrie Christophe , Troche Gilles , Timsit Jean-François 
Published: November 2003

Background
The authors prospectively evaluated the occurrence and outcomes of unplanned extubations (self-extubation and accidental extubation) and reintubation after weaning, and examined the hypothesis that these events may differ regarding their influence on the risk of nosocomial pneumonia.

Methods
Data were taken from a prospective, 2-yr database including 750 mechanically ventilated patients from six intensive care units.

Results
One hundred five patients (14%) experienced at least one episode of these 3 events; 51 self-extubations occurred in 38 patients, 24 accidental extubations in 22 patients, and 56 reintubations after weaning in 45 patients. The incidence density of these 3 events was 16.4 per 1,000 mechanical ventilation days. Reintubation within 48 h was needed consistently after accidental extubation but was unnecessary in 37% of self-extubated patients. Unplanned extubation and reintubation after weaning were associated with longer total mechanical ventilation (17 vs. 6 days; P < 0.0001), intensive care unit stay (22 vs. 9 days; P < 0.0001), and hospital stay (34 vs. 18 days; P < 0.0001) than in control group, but did not influence intensive care unit or hospital mortality. The incidence of nosocomial pneumonia was significantly higher in patients with unplanned extubation or reintubation after weaning (27.6% vs. 13.8%; P = 0.002). In a Cox model adjusting on severity at admission, unplanned extubation and reintubation after weaning increased the risk of nosocomial pneumonia (relative risk, 1.80; 95% confidence interval, 1.15-2.80; P = 0.009). This risk increase was entirely ascribable to accidental extubation (relative risk, 5.3; 95% confidence interval, 2.8-9.9; P < 0.001).

Conclusion
Accidental extubation but not self-extubation or reintubation after weaning increased the risk of nosocomial pneumonia. These 3 events may deserve evaluation as an indicator for quality-of-care studies.
Esmolol Improves Left Ventricular Function via Enhanced β-Adrenergic Receptor Signaling in a Canine Model of Coronary Revascularization
Authors: Booth John V. , Spahn Donat R. , McRae Robert L. , Chesnut Lynn C. , El-Moalem Habib , Atwell Darryl M. , Leone Bruce J. , Schwinn Debra A. 
Published: November 2003

Background
Recent American Heart Association guidelines highlight the paucity of data on effectiveness and/or mechanisms underlying use of beta-adrenergic receptor (beta AR) antagonists after acute coronary syndromes in patients subsequently undergoing revascularization. It is important to assess whether beta AR antagonists might protect the heart and improve ventricular function in this scenario. The authors therefore used esmolol (an ultra-short-acting beta AR antagonist) to determine whether beta AR antagonist treatment improves left ventricular function in a canine model of acute reversible coronary ischemia followed by coronary reperfusion during cardiopulmonary bypass (CPB). The authors also tested whether the mechanism includes preserved beta AR signaling.

Methods
Dogs were randomized to either esmolol or saline infusions administered during CPB (n = 29). Pre-CPB and end-CPB transmyocardial left ventricular biopsies were obtained; plasma catecholamine concentrations, myocardial beta AR density, and adenylyl cyclase activity were measured. In addition, left ventricular systolic shortening and postsystolic shortening were determined immediately prior to each biopsy.

Results
While beta AR density remained unchanged in each group, isoproterenol-stimulated adenylyl cyclase activity decreased 26 +/- 6% in the control group but increased 38 +/- 10% in the esmolol group (pre-CPB to end-CPB, mean +/- SD, P = 0.0001). Left ventricular systolic shortening improved in both groups after release of coronary (LAD) ligature; however, the esmolol group increased to 72 +/- 23% of pre-CPB values compared to 48 +/- 12% for the control group (P = 0.0008).

Conclusions
These data provide prospective evidence that esmolol administration results in improved myocardial function. Furthermore, the mechanism appears to involve enhanced myocardial beta AR signaling.
Effect of Intrathecal Non-NMDA EAA Receptor Antagonist LY293558 in Rats
Authors: Von Bergen Nicholas H. , Subieta Alberto , Brennan Timothy J. 
Published: November 2003

Background
Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia.

Methods
Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 microl bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558.

Results
Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558.

Conclusion
Drugs like LY293558 that block alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.
Influence of Lung Aeration on Pulmonary Concentrations of Nebulized and Intravenous Amikacin in Ventilated Piglets with Severe Bronchopneumonia
Authors: Elman Marilia , Goldstein Ivan , Marquette Charles-Hugo , Wallet Fréderic , Lenaour Gilles , Rouby Jean-Jacques 
Published: November 2003

Background
Pulmonary concentrations of aminoglycosides administered intravenously are usually low in the infected lung parenchyma. Nebulization represents an alternative to increase pulmonary concentrations, although the obstruction of bronchioles by purulent plugs may impair lung deposition by decreasing lung aeration.

Methods
An experimental bronchopneumonia was induced in anesthetized piglets by inoculating lower lobes with a suspension of 10(6) cfu/ml Escherichia coli. After 24 h of mechanical ventilation, 7 animals received two intravenous injections of 15 mg/kg amikacin, and 11 animals received two nebulizations of 40 mg/kg amikacin at 24-h intervals. One hour following the second administration, animals were killed, and multiple lung specimens were sampled for assessing amikacin pulmonary concentrations and quantifying lung aeration on histologic sections.

Results
Thirty-eight percent of the nebulized amikacin (15 mg/kg) reached the tracheobronchial tree. Amikacin pulmonary concentrations were always higher after nebulization than after intravenous administration, decreased with the extension of parenchymal infection, and were significantly influenced by lung aeration: 197 +/- 165 versus 6 +/- 5 microg/g in lung segments with focal bronchopneumonia (P = 0.03), 40 +/- 62 versus 5 +/- 3 microg/g in lung segments with confluent bronchopneumonia (P = 0.001), 18 +/- 7 versus 7 +/- 4 microg/g in lung segments with lung aeration of 30% or less, and 65 +/- 9 versus 2 +/- 3 microg/g in lung segments with lung aeration of 50% or more.

Conclusions
In a porcine model of severe bronchopneumonia, the nebulization of amikacin provided 3-30 times higher pulmonary concentrations than the intravenous administration of an equivalent dose. The greater the lung aeration, the higher were the amikacin pulmonary concentrations found in the infected lung segments.