bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Spinal Neurotoxicity of Prilocaine and Lidocaine
Authors: Kishimoto Tomomune , Bollen Andrew W. , Drasner Kenneth 
Published: November 2003

Background
Reports of major and minor sequelae following lidocaine spinal anesthesia have generated interest in an alternative short-acting intrathecal agent. Of the available anesthetics suitable for short-duration spinal anesthesia, prilocaine is perhaps the most promising agent. However, data comparing the neurotoxicity of these agents are lacking. Accordingly, the present experiments investigate whether prilocaine and lidocaine differ with respect to sensory impairment and histologic damage when administered intrathecally in the rat.

Methods
Ninety rats were divided into three groups to receive an intrathecal infusion of 2.5% prilocaine in saline, 2.5% lidocaine in saline, or normal saline. The animals were assessed for persistent sensory impairment 4 days after anesthetic administration using the tail-flick test. Three days later, the animals were killed, and specimens of the spinal cord and nerve roots were obtained for histopathologic examination.

Results
Prilocaine and lidocaine produced equivalent elevations in tail-flick latency that differed significantly from saline. Histologic injury scores with prilocaine were greater than with lidocaine, but this difference did not reach statistical significance.

Conclusions
The propensity for persistent functional impairment or morphologic damage with intrathecal prilocaine is at least as great as with lidocaine. Although the substitution of prilocaine for lidocaine may reduce the incidence of transient neurologic symptoms, it is unlikely to reduce the risk of actual neural injury. This discrepancy may indicate that transient neurologic symptoms and neurologic deficits after spinal anesthesia are not mediated by the same mechanism.
Effects of Isoflurane on γ-Aminobutyric Acid Type A Receptors Activated by Full and Partial Agonists
Authors: Topf Norbert , Jenkins Andrew , Baron Nicole , Harrison Neil L. 
Published: November 2003

Background
Volatile anesthetics prolong inhibitory postsynaptic potentials in central neurons an allosteric action on the gamma-aminobutyric acid type A (GABA(A)) receptor, an effect that may underlie the hypnotic actions of these agents. Inhaled anesthetics such as isoflurane act to enhance responses to submaximal concentrations of GABA, but it is not clear whether their effect is mediated by an increase in the binding of the agonist or by changes in receptor gating behavior. To address this question, the authors studied the effects of isoflurane on a mutant GABA(A) receptor with a gating defect that decreases receptor sensitivity by lowering agonist efficacy. They then compared the effects of clinically relevant concentrations of isoflurane on the actions of GABA and piperidine-4-sulfonic acid (P4S), a partial agonist at the GABA(A) receptor.

Methods
The authors created a mutant of the GABA receptor alpha subunit (L277A) by site-directed mutagenesis. The mutant subunit was coexpressed with beta(2) and gamma(2S) subunits in HEK293 cells, and responses to GABA and P4S were recorded using the whole-cell patch clamp technique. EC values were determined for the full agonist GABA and the partial agonist P4S. The authors also determined the relative efficacy (epsilon) of P4S. These measurements were then repeated in the presence of isoflurane.

Results
The concentration-response curve for GABA was shifted to the right (EC(50) = 278 microm) in the alpha(1)(L277A)beta(2)gamma(2S) mutant receptor, compared with the corresponding wild-type alpha(1)beta(2)gamma(2S) GABA(A) receptor (EC(50) = 16 microm). P4S is a partial agonist at both receptors, with a dramatically decreased relative efficacy at the mutant receptor (epsilon = 0.24). When the mutant receptor was studied in the presence of isoflurane, the concentration-response curves for both GABA and P4S were shifted to the left (EC(50) for GABA = 78 microm); the efficacy of P4S also increased significantly (epsilon = 0.40).

Conclusion
By studying a mutant GABA receptor with impaired gating, the authors were able to demonstrate clearly that isoflurane can increase the efficacy of a partial agonist, as well as increase agonist potency. These data suggest that the volatile anesthetic isoflurane exerts at least some of its effects on the GABA(A) receptor via alterations in gating rather than simply changing binding or unbinding of the agonist.
Cardiopulmonary Bypass Decreases G Protein–Coupled Receptor Kinase Activity and Expression in Human Peripheral Blood Mononuclear Cells
Authors: Hagen Scott A. , Kondyra Amy L. , Grocott Hilary P. , El-Moalem Habib , Bainbridge Daniel , Mathew Joseph P. , Newman Mark F. , Reves Joseph G. , Schwinn Debra A. , Kwatra Madan M. 
Published: November 2003

Background
Cardiopulmonary bypass (CPB) has been implicated in the development of organ injury associated with cardiac surgery. At the molecular level, CPB is accompanied by a pronounced proinflammatory response including an increase in plasma interleukin (IL)-6. The IL-6 has been shown to be increased in rheumatoid arthritis, a chronic inflammatory disease, where it has been implicated in decreasing G protein-coupled receptor kinases (GRKs) in peripheral blood mononuclear cells. Since IL-6 is substantially increased after CPB, the study tested whether the increase of IL-6 during CPB leads to a decrease of GRKs in mononuclear cells. This is important because GRKs regulate the function of G protein-coupled receptors involved in inflammation.

Methods
Fifteen patients had blood withdrawn before CPB, 2 h after CPB, and on postoperative day one (POD1). Plasma IL-6 concentrations were determined by enzyme-linked immunosorbent assay. The GRK protein expression and activity were determined by Western blot and phosphorylation of rhodopsin using [gamma-(32)P] adenosine triphosphate, respectively.

Results
Plasma IL-6 increased over 20-fold after CPB and remained increased on POD1. Cytosolic GRK activity in mononuclear cells decreased by 39 +/- 29%; cytosolic GRK2 and membrane-bound GRK6 decreased by 90 +/- 15 and 65 +/- 43%, respectively. The GRK activity and expression of GRK2/GRK6 on POD1 returned to basal levels in many but not all patients.

Conclusions
The CPB causes a profound decrease in mononuclear cell GRKs, and the recovery of these kinases on POD1 is quite variable. The significance of the variable recovery of GRKs after CPB and their potential role as a marker of clinical outcome deserves further investigation.
The Parker Flex-Tip Tube versus a Standard Tube for Fiberoptic Orotracheal Intubation
Authors: Kristensen Michael S. 
Published: November 2003

Background
During fiberoptic tracheal intubation, passage of the fiberscope itself to the trachea is often fairly easy, but passage of the tube into the trachea may be difficult or even impossible. A new type of disposable endotracheal tube, the Parker Flex-Tip tube, has a tip that reduces the gap between the fiberscope and the inside of the tube. Thus, theoretically, a smaller risk of impinging on laryngeal structures during insertion in trachea is expected.

Methods
Eighty patients scheduled for elective anesthesia using orotracheal intubation were randomized to either a Parker Flex-Tip tube or a standard (Portex) 7.5-mm-ID endotracheal tube. Blinding was obtained by having the tube premounted on the fiberscope (Olympus LF-1; diameter of fiberscope = 4 mm) and thereafter covered with a black opaque plastic bag. Difficulty in placing the tube was scored using an objective standardized grading system.

Results
Seventy-six patients completed the study. The use of the Parker Flex-Tip tube reduced the incidence of need for repositioning of the tube during insertion into trachea from 89% to 29% (P < 0.0001) when compared to the standard tube. The median time for passage of the tube into the trachea was reduced from 20 s to 7.5 s (P < 0.0001).

Conclusions
During oral fiberoptic intubation, the use of the Parker Flex-Tip tube is associated with greater incidence of initial success of passage of the tube into trachea when compared to a standard endotracheal tube.
Hepatic Ischemia Is Associated with an Increase in Liver Parenchyma Nitric Oxide That Is in Part Enzyme-Independent
Authors: Lhuillier Franck , Parmantier Pierre , Goudable Joelle , Crova Philippe , Delafosse Bertrand , Annat Guy , Cespuglio Raymond , Viale Jean Paul 
Published: November 2003

Background
Nitric oxide (NO) might be involved in liver response to local ischemia-reperfusion injury.

Methods
A specific NO-sensitive electrode was inserted into liver parenchyma of anesthetized rabbits. After a 45-min period of stable NO signal, the vascular pedicle of the caudal lobe of the liver was clamped for 45 min, then the clamp was removed. Perfusion of the right upper lobe was left unchanged. The same procedure was applied in other animals after administration of a long-acting nonspecific NO synthase inhibitor NAPNA.

Results
Occlusion of the caudal pedicle was associated with a mean threefold increase in NO signal measured in the caudal lobe. After unclamping, this signal returned within 8 min to baseline value and remained stable for the next 6 h. In the right upper lobe, NO signal was unaffected by caudal lobe ischemia. By the end of the 6-h reperfusion period, administration of the NO inhibitor l-NAME led to a suppression of the NO signal, thus demonstrating the specificity of the measurement. Plasma nitrate and nitrite concentrations remained almost unchanged during the study period in all groups. In animals whose NO synthases had been previously inhibited by NAPNA, clamping the caudal pedicle for 45 min was still associated with a significant increase in caudal lobe NO signal.

Conclusion
Nitric oxide is present in liver parenchyma, and its generation is dramatically affected by an ischemia injury. The increased NO generation during local ischemia is, at least in part, independent of NO synthases.
Respiratory Depression by Tramadol in the Cat
Authors: Teppema Luc J. , Nieuwenhuijs Diederik , Olievier Cees N. , Dahan Albert 
Published: November 2003

Background
Tramadol hydrochloride (tramadol) is a synthetic opioid analgesic with a relatively weak affinity at opioid receptors. At analgesic doses, tramadol seems to cause little or no respiratory depression in humans, although there are some conflicting data. The aim of this study was to examine whether tramadol causes dose-dependent inhibitory effects on the ventilatory carbon dioxide response curve and whether these are reversible or can be prevented by naloxone.

Methods
Experiments were performed in cats under alpha-chloralose-urethane anesthesia. The effects of tramadol and naloxone were studied by applying square-wave changes in end-tidal pressure of carbon dioxide (Petco2; 7.5-11 mmHg) and by analyzing the dynamic ventilatory responses using a two-compartment model with a fast peripheral and a slow central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and a single offset (apneic threshold).

Results
In five animals 1, 2, and 4 mg/kg tramadol (intravenous) increased the apneic threshold (control: 28.3 +/- 4.8 mmHg [mean +/- SD]; after 4 mg/kg: 36.7 +/- 7.1 mmHg; P < 0.05) and decreased the total carbon dioxide sensitivity (control: 109.3 +/- 41.3 ml x min(-1) x mmHg(-1) ) by 31, 59, and 68%, respectively, caused by proportional equal reductions in sensitivities of the peripheral and central chemoreflex loops. Naloxone (0.1 mg/kg, intravenous) completely reversed these effects. In five other cats, 4 mg/kg tramadol caused an approximately 70% ventilatory depression at a fixed Pet co2 of 45 mmHg that was already achieved after 15 min. A third group of five animals received the same dose of tramadol after pretreatment with naloxone. At a fixed Petco of 45 mmHg, naloxone prevented more than 50% of the expected ventilatory depression in these animals.

Conclusions
Because naloxone completely reversed the inhibiting effects of tramadol on ventilatory control and it prevented more than 50% of the respiratory depression after a single dose of tramadol, the authors conclude that this analgesic causes respiratory depression that is mainly mediated by opioid receptors.
Ketamine and Midazolam Differentially Inhibit Nonadrenergic Noncholinergic Lower Esophageal Sphincter Relaxation in Rabbits
Authors: Kohjitani Atsushi , Miyawaki Takuya , Funahashi Makoto , Higuchi Hitoshi , Matsuo Ryuji , Shimada Masahiko 
Published: November 2003

Background
The authors previously reported that ketamine and midazolam inhibited nitric oxide-mediated nonadrenergic noncholinergic (NANC) lower esophageal sphincter (LES) relaxation nitric oxide-3',5'-cyclic guanosine monophosphate pathway modulation. The mechanisms inhibiting the NANC relaxation by ketamine and midazolam were investigated.

Methods
The isometric tension of circular distal esophageal muscle strips from Japanese White rabbits was examined. NANC relaxation was induced by KCl (30 mm) in the presence of atropine (3 x 10(-6) m) and guanethidine (3 x 10(-6) m). Nitric oxide synthase activity in the absence and presence of ketamine and midazolam was analyzed using the biochemical conversion of L-[3H]arginine to L-[3H]citrulline.

Results
The ketamine-induced inhibition of the NANC relaxation was partly reversed by superoxide dismutase (200, 400 U/ml) but not by catalase (100 U/ml). Ketamine concentration-dependently inhibited the relaxation induced by N-ethylethanamine:1,1-diethyl-2-hydroxy-2-nitrosohydrazine (diethylamine NONOate) and S-nitrosoglutathione. The NANC relaxation itself was not affected by superoxide dismutase. The midazolam-induced inhibition of the NANC relaxation was reversed neither by superoxide dismutase nor by catalase, and midazolam did not affect the relaxations induced by nitric oxide donors. The nitric oxide synthase activity was concentration-dependently suppressed by midazolam, but there was no marked effect of ketamine. Pyrogallol, a superoxide generator, inhibited the NANC and the diethylamine NONOate-induced relaxations. The pyrogallol-induced inhibition of the NANC relaxation was reversed by superoxide dismutase.

Conclusion
These findings suggest that ketamine inhibits NANC LES relaxation by the extracellular production of superoxide anion, and that midazolam inhibits it by the inhibition of nitric oxide synthase activity.
Nociception in Persistent Pancreatitis in Rats
Authors: Vera-Portocarrero Louis P. , Lu Ying , Westlund Karin N. 
Published: November 2003

Background
Most animal models of pancreatitis are short-lived or very invasive. A noninvasive animal model of pancreatitis developed in highly inbred rats by Merkord with symptoms persisting for 3 weeks was adopted in the current study to test its validity as a model of visceral pain in commercially available rats.

Methods
The persistent pancreatitis model was established by tail vein injection of dibutyltin dichloride. Animals were given 10% alcohol in their drinking water to enhance the pancreatitis attack. Blood serum pancreatic enzymes and nociceptive state were monitored for 3 weeks after dibutyltin dichloride or vehicle. Behavioral testing included reflexive withdrawal to mechanical and thermal stimulation of the abdominal area. The effect of morphine on nociceptive behaviors was tested. Histologic analysis of the pancreas and immunohistochemical analysis of substance P and calcitonin gene-related peptide in the spinal cord are included in the study.

Results
Compared with naïve and vehicle-only injected control groups, rats receiving dibutyltin dichloride demonstrated an increase in withdrawal events after von Frey stimulation and decreased withdrawal latency after thermal stimulation, signaling a sensitized nociceptive state through 7 days. These pain-related measures were abrogated by morphine. Blood serum concentrations of amylase and lipase as well as tissue inflammatory changes and substance P were also significantly elevated during this same time period.

Conclusions
These results indicate that animals with the dibutyltin dichloride-induced experimental pancreatitis expressed serum, histologic, and behavioral characteristics similar in duration to those present during acute attacks experienced by patients with chronic pancreatitis. These findings and responsivity to morphine suggest the utility of this model developed in a commercially available strain of rats for study of persistent visceral pain.
Sustained Prolongation of the QTc Interval after Anesthesia with Sevoflurane in Infants during the First 6 Months of Life
Authors: Loeckinger Alex , Kleinsasser Axel , Maier Stephan , Furtner Bernhard , Keller Christian , Kuehbacher Gabriele , Lindner Karl H. 
Published: November 2003

Background
Sevoflurane, an inhalational anesthetic frequently administered to infants, prolongs the QT interval of the electrocardiogram in adults. A long QT interval resulting in fatal arrhythmia may also be responsible for some cases of sudden death in infants. As the QT interval increases during the second month of life and returns to the values recorded at birth by the sixth month, we evaluated the effect of sevoflurane on the QT interval during and after anesthesia in this particular population.

Methods
In this prospective two-group trial we examined pre-, peri-, and postoperative electrocardiograms of 36 infants aged 1 to 6 months scheduled for elective inguinal or umbilical hernia repair. Anesthesia was induced and maintained with either sevoflurane, or the well-established pediatric anesthetic halothane. Heart rate corrected (c) QTc and JTc interval (indicator of intraventricular conduction delays) were recorded from electrocardiograms before and during anesthesia, and at 60 min after emergence from anesthesia.

Results
Prolonged QTc was observed during sevoflurane anesthesia (mean [+/-SD], 473 +/- 19 ms, P< 0.01). Sixty minutes after emergence from anesthesia, QTc was still prolonged (433 +/- 15 ms) in infants treated with sevoflurane compared with those treated with halothane (407 +/- 33 ms, P< 0.01). Analogous differences were found for the JTc interval.

Conclusions
Despite a shorter elimination time than better known inhalational anesthetics, sevoflurane induction and anesthesia results in sustained prolongations of QTc and JTc interval in infants in the first 6 months of life. Electrocardiogram monitoring until the QTc interval has returned to preanesthetic values may increase safety after sevoflurane anesthesia.
Randomized Assessment of Resource Use in Fast-track Cardiac Surgery 1-Year after Hospital Discharge
Authors: Cheng Davy C. H. , Wall Claus , Djaiani George , Peragallo Raul A. , Carroll Jo , Li Cindy , Naylor David 
Published: November 2003

Background
The authors assessed the safety and resource use associated with fast-track cardiac anesthesia (FTCA) after coronary artery bypass graft surgery (CABG) over a 1-yr period.

Methods
One hundred twenty patients were initially randomized to FTCA (n = 60) or conventional anesthetic (n = 60) for primary elective CABG surgery. Patients were followed for 1-yr after index surgery through linkage to universal administrative databases. Acute care hospital readmission rates and length of stay (LOS) and the downstream use of health resources were compared. Resource use was analyzed as use of hospital and rehabilitation center bed-days, expenditures on physician services, and use of cardiac drugs.

Results
There were no deaths during the 1-yr follow-up after initial discharge; 15 (25%) patients from both groups were readmitted to acute care hospitals in the follow-up period. The mean LOS for acute care readmission was 0.3 (1.0) in the FTCA and 1.6 (6.3) days in the conventional group at 3 months; P= 0.01, 95% CI (0.1, 5.7) and 0.8 (1.8) and 2.9 (9.6) days at 12 months; P= 0.01, 95% CI (0.2, 7.5). Two (3.3%) patients in the FTCA group and 9 (15%) patients in the conventional group were transferred to rehabilitation facilities. The LOS was 0.3 (1.5) and 2.3 (5.7) days respectively; P= 0.001, 95% CI (0.6, 4.0). Specialist visits were more frequent in the FTCA group 6.2 (13.2) versus 1.9 (2.2) visits respectively; P= 0.002, 95% CI (-9.0, -1.3). Percentage reduction of FTCA cost was 68% at 3 months, P= 0.0002 and 49.5% at 1-yr, P= 0.004 after index hospital discharge.

Conclusions
Fast-track cardiac anesthesia is a safe practice that decreases resource use for a 1-yr period after index hospitalization.
Isoflurane but Not Mechanical Ventilation Promotes Extravascular Fluid Accumulation during Crystalloid Volume Loading
Authors: Connolly Cara M. , Kramer George C. , Hahn Robert G. , Chaisson Neil F. , Svensén Christer H. , Kirschner Robert A. , Hastings Dennis A. , Chinkes David L. , Prough Donald S. 
Published: November 2003

Background
The combination of isoflurane anesthesia and mechanical ventilation reduces urinary output and promotes redistribution of a crystalloid bolus into the extravascular space. The authors hypothesized that mechanical ventilation rather than isoflurane causes this alteration.

Methods
The fate of a 25-ml/kg, 20-min, 0.9% saline fluid bolus was studied in four different experiments per sheep: while conscious and spontaneously ventilating (CSV), while conscious and mechanically ventilated (CMV), while anesthetized with isoflurane and mechanical ventilated (ISOMV), and while anesthetized with isoflurane and spontaneously ventilating (ISOSV).

Results
By calculations based on the indicator dilution and mass balance principles, plasma expansion was similar between protocols. Isoflurane but not mechanical ventilation reduced urinary output and increased interstitial fluid volume (P < 0.001): At 180 min, mean total urinary outputs were 15.6 +/- 2.1 and 15.9 +/- 2.9 ml/kg in the CSV and CMV protocols and 2.7 +/- 0.6 and 3.1 +/- 1.1 ml/kg in the ISOSV and ISOMV protocols, respectively. The net changes in extravascular volume, assumed to be interstitial fluid volume, were 8.6 +/- 3.3 and 8.1 +/- 3.1 ml/kg, and 22.5 +/- 1.5 and 22.1 +/- 1.6 ml/kg in the corresponding protocols. Volume kinetic analysis demonstrated extravascular fluid accumulation associated with isoflurane anesthesia similar to the calculated interstitial accumulation of 20.2 +/- 0.5 and 26.5 +/- 0.3 ml/kg in the ISOSV and ISOMV protocols, respectively.

Conclusion
Isoflurane, but not mechanical ventilation, decreased urinary excretion and increased interstitial fluid volume. Volume kinetic analysis indicated "third-space" losses due to isoflurane. Perioperative fluid retention may be associated not only with surgical tissue manipulation, but with anesthesia per se.