bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetic Modulation of HERG Potassium Channels by the Volatile Anesthetic Halothane
Authors: Li Jichang , Correa Ana M. 
Published: November 2003

Background
(human ether-a-gogo related gene) encodes the cardiac rapidly activating delayed rectifier potassium currents (I(kr)), which play an important role in cardiac action potential repolarization. General anesthetics, like halothane, can prolong Q-T interval, suggesting that they act on myocellular repolarization, possibly involving HERG channels. Evidence for direct modulation of HERG channels by halothane is still lacking. To gain insight on HERG channel modulation by halothane the authors recorded macroscopic currents expressed in Xenopus oocytes and conducted non-stationary noise analysis to evaluate single channel parameters modified by the anesthetic.

Methods
Macroscopic currents were recorded in 120 mM K(+) internal-5 mM K(+) external solutions with the cut open oocyte technique. Macropatch recordings for non-stationary noise analysis of HERG tail currents were made in symmetrical 120 mM K(+) solutions. Pulse protocols designed for HERG current recording were elicited from a holding potential of -80 mV. Halothane was delivered via gravity-fed perfusion.

Results
Halothane (0.7%, 1.5%, and 3%) decreased macroscopic currents in a concentration-dependent manner (average reduction by 14%, 22%, and 35% in the range of -40 mV to 40 mV) irrespective of potential. HERG currents had slower activation and accelerated deactivation and inactivation. Non-stationary noise analysis revealed that halothane, 1.5%, decreased channel P(o) by 27%, whereas single-channel current amplitudes and number of channels in the patch remained unchanged.

Conclusions
Halothane inhibits HERG currents expressed in oocytes in a concentration-dependent manner. It slowed down activation and accelerated deactivation and inactivation of HERG channels. The authors' results demonstrate that halothane decreased HERG currents by modulating kinetic properties of HERG channels, decreasing their open probability. Partial block of I(kr) currents could contribute to delayed myocellular repolarization and altered cardiac electrophysiology.
The Anabolic Effect of Epidural Blockade Requires Energy and Substrate Supply
Authors: Schricker Thomas , Wykes Linda , Eberhart Leopold , Lattermann Ralph , Mazza Louise , Carli Franco 
Published: November 2003

Background
The authors examined the hypothesis that continuous thoracic epidural blockade with local anesthetic and opioid, in contrast to patient-controlled intravenous analgesia with morphine, stimulates postoperative whole body protein synthesis during combined provision of energy (4 mg x kg(-1) x min(-1) glucose) and amino acids (0.02 ml x kg(-1) x min(-1) Travasol 10%, equivalent to approximately 2.9 g x kg(-1) x day(-1)).

Methods
Sixteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding) on the second day after colorectal surgery performed with or without perioperative epidural blockade. Protein synthesis, breakdown and oxidation, glucose production, and clearance were measured by L-[1-(13)C]leucine and [6,6-(2)H(2) ]glucose.

Results
Epidural blockade did not affect protein and glucose metabolism in the fasted state. Parenteral alimentation decreased endogenous protein breakdown and glucose production to the same extent in both groups. Administration of glucose and amino acids was associated with an increase in whole body protein synthesis that was modified by the type of analgesia, i.e., protein synthesis increased by 13% in the epidural group (from 93.3 +/- 16.6 to 104.5 +/- 11.1 micromol x kg(-1) x h(-1) ) and by 4% in the patient-controlled analgesia group (from 90.0 +/- 27.1 to 92.9 +/- 14.8 micromol x kg(-1) x h(-1);P = 0.054).

Conclusions
Epidural blockade accentuates the stimulating effect of parenteral alimentation on whole body protein synthesis.
Continuous Popliteal Sciatic Nerve Block for Postoperative Pain Control at Home
Authors: Ilfeld Brian M. , Morey Timothy E. , Wang R. Doris , Enneking F. Kayser 
Published: November 2003

Background
This randomized, double-blinded, placebo-controlled study investigated the efficacy of patient-controlled regional analgesia using a sciatic perineural catheter in the popliteal fossa and a portable infusion pump for outpatients having moderately painful, lower extremity orthopedic surgery.

Methods
Preoperatively, patients (n = 30) received a sciatic nerve block and perineural catheter in the popliteal fossa. Postoperatively, patients were discharged with both oral opioids and a portable infusion pump delivering study solution (0.2% ropivacaine or 0.9% saline) via the catheter for 3 days. Investigators and patients were blinded to random group assignment. Daily end-points included pain scores, opioid use and side effects, sleep quality, and symptoms of catheter- or local anesthetic-related complications.

Results
Ropivacaine (n = 15) infusion significantly reduced pain compared with saline (n = 15) infusion ( < 0.001). For example, the average pain at rest (scale: 0-10) on postoperative day 1 (median, 25th -75th percentile) was 4.0 (3.5-5.5) for the saline group, versus 0.0 (0.0-0.0) for the ropivacaine group (P < 0.001). Oral opioid use and related side effects were significantly decreased in the ropivacaine group. For example, on postoperative day 1, median tablet consumption was 8.0 (5.0-10.0) and 0.0 (0.0-0.0) for the saline and ropivacaine groups, respectively (P < 0.001). Sleep disturbance scores were more than 10-fold greater for saline administration than for ropivacaine infusion (P < 0.001). Overall satisfaction was significantly greater in the ropivacaine group. Other than two inadvertent catheter dislodgements, no catheter- or local anesthetic-related complications occurred.

Conclusions
After moderately painful orthopedic surgery of the lower extremity, ropivacaine infusion using a portable mechanical pump and a popliteal sciatic perineural catheter at home decreased pain, opioid use and related side effects, sleep disturbances, and improved overall satisfaction.
Pharmacology of Opioid Inhibition to Noxious Uterine Cervical Distension
Authors: Sandner-Kiesling Andreas , Eisenach James C. 
Published: November 2003

Background
Reflex abdominal muscle contraction elicited by colorectal distension in male rats is inhibited by mu- and kappa-opioid receptor agonists and sites of action and receptor subtypes have been probed. The authors examined the pharmacology of opioid agonist inhibition in visceral pain related to the uterine cervix, the source of labor pain.

Methods
Ovariectomized female rats were anesthetized with halothane, and metal rods inserted in the uterine cervix through a small midline laparotomy. After a period of stabilization the cervix was distended by manual separation of the rods, using stimuli of 25-100 g, and reflex rectus abdominis electromyographic activity was recorded. After determining the stimulus response relationship, we tested inhibition of reflex activity by -U50,488 and morphine and their reversal with norbinaltorphimine, or with naltrexone and methyl-naltrexone, respectively.

Results
Cervical distension produced a stimulus-dependent increase in electromyographic activity, with a threshold of 25 g. Morphine and -U50,488 produced dose-dependent inhibition of the reflex activity. Log linear regression analysis demonstrated an ID50 of 0.03 for morphine, and of 0.05 mg/kg for -U50,488. These effects were reversed by naltrexone, but not by methylnaltrexone or norbinaltorphimine.

Conclusions
These data suggest that mu- and kappa-opioid receptor agonists effectively inhibit responses to acute uterine cervical stimulation. Lack of reversal by norbinaltorphimine further supports evidence of a novel kappa-opioid receptor by visceral afferents. Lack of morphine reversal by methylnaltrexone suggests central (spinal or supraspinal) sites of action for inhibition of this visceral noxious stimulus.
Concentration–Effect Relation of Succinylcholine Chloride during Propofol Anesthesia
Authors: Roy Julie J. , Donati François , Boismenu Daniel , Varin France 
Published: November 2003

Background
The pharmacokinetics and pharmacodynamics of succinylcholine were studied simultaneously in anesthetized patients to understand why the drug has a rapid onset and short duration of action. A quantitative model describing the concentration-effect relation of succinylcholine was proposed. The correlation between hydrolysis in plasma and elimination was also examined.

Methods
Before induction of anesthesia, blood was drawn for analysis in seven adults. Anesthesia was induced with propofol and remifentanil. Single twitch stimulation was applied at the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis was measured. Arterial blood was drawn frequently after succinylcholine injection to characterize the front-end kinetics. Plasma concentrations were measured by mass spectrometry, and pharmacokinetic parameters were derived using compartmental and noncompartmental approaches. Pharmacokinetic-pharmacodynamic relations were estimated.

Results
The mean degradation rate constant in plasma (1.07 +/- 0.49 min(-1)) was not different from the elimination rate constant (0.97 +/- 0.30 min(-1)), and an excellent correlation (r2 = 0.94) was observed. Total body clearance derived using noncompartmental (37 +/- 7 ml x min(-1) x kg(-1)) and compartmental (37 +/- 9 ml x min(-1) x kg(-1)) approaches were similar. The plasma-effect compartment equilibration rate constant (k(eo)) was 0.058 +/- 0.026 min(-1), and the effect compartment concentration at 50% block was 734 +/- 211 ng/ml.

Conclusion
Succinylcholine is a low-potency drug with a very fast clearance that equilibrates relatively slowly with the effect compartment. Its disappearance is greatly accountable by a rapid hydrolysis in plasma.
Renal Responses to Desflurane and Isoflurane in Patients with Renal Insufficiency
Authors: Litz Rainer J. , Hübler Matthias , Lorenz Wolfram , Meier Volker K. , Albrecht D. Michael 
Published: November 2003

Background
The most consistent risk factor for postoperative renal failure is poor preoperative renal function. Desflurane is not contraindicated in patients with renal disease, but the data regarding its effects on renal function in these patients are sparse.

Methods
Only patients with preexisting renal disease were recruited into the study. In 51 adults undergoing elective surgery, general anesthesia was maintained using randomly desflurane or isoflurane according to a standardized protocol. Creatinine, creatinine clearance, and blood urea nitrogen were measured pre- and postoperatively.

Results
The administered amounts of the inhaled anesthetic agents were 1.8 +/- 2.1 minimum alveolar concentration hours (mean +/- SD) of isoflurane (24 patients) and 2.2 +/- 1.8 minimum alveolar concentration hours of desflurane (27 patients), respectively. No deterioration in renal parameters was noted when comparing the pre- and postoperative values between the groups and within the groups over time.

Conclusion
General anesthesia with desflurane or isoflurane did not aggravate renal impairment in patients with preexisting renal insufficiency.
Remifentanil Requirements during Sevoflurane Administration to Block Somatic and Cardiovascular Responses to Skin Incision in Children and Adults
Authors: Muñoz Hernán R. , Cortínez Luis I. , Altermatt Fernando R. , Dagnino Jorge A. 
Published: November 2003

Background
The authors found no studies comparing intraoperative requirements of opioids between children and adults, so they determined the infusion rate of remifentanil to block somatic (IR50) and autonomic response (IRBAR50) to skin incision in children and adults.

Methods
Forty-one adults (aged 20-60 yr) and 24 children (aged 2-10 yr) undergoing lower abdominal surgery were studied. In adults, anesthesia induction was with sevoflurane during remifentanil infusion, whereas in children remifentanil administration was started after induction with sevoflurane. After intubation, sevoflurane was administered in 100% O2 and was adjusted to an ET% of 1 MAC-awake corrected for age at least 15 min before surgery. Patients were randomized to receive remifentanil at a rate ranging from 0.05 to 0.35 microg x kg(-1) x min(-1) for at least 20 min before surgery. At the beginning of surgery, only the skin incision was performed, and the somatic and autonomic responses were observed. The somatic response was defined as positive with any gross movement of extremity, and the autonomic response was deemed positive with any increase in heart rate mean arterial pressure equal to or more than 10% of preincision values. Using logistic regression, the IR50 and IRBAR50 were determined in both groups of patients and compared with unpaired Student t test. A P value less than 0.05 was considered significant.

Results
The IR50 +/- SD was 0.10 +/- 0.02 microg x kg(-1) x min(-1) in adults and 0.22 +/- 0.03 microg x kg(-1) x min(-1) in children (P < 0.001). The IRBAR50 +/- SD was 0.11 +/- 0.02 microg x kg(-1) x min(-1) in adults and 0.27 +/- 0.06 microg x kg(-1) x min(-1) in children (P < 0.001).

Conclusions
To block somatic and autonomic responses to surgery, children require a remifentanil infusion rate at least twofold higher than adults.
Sulfite Supported Lipid Peroxidation in Propofol Emulsions
Authors: Baker Max T. , Dehring Deborah J. , Gregerson Marc S. 
Published: November 2003

Background
Sodium metabisulfite is added to a commercial propofol emulsion as an antimicrobial agent. The sulfite ion (SO3(-2)) is capable of undergoing a number of reactions, including autooxidation and the promotion of lipid peroxidation. This study evaluated sulfite reactivity in propofol emulsions by determining thiobarbituric acid reacting substances (TBARS), sulfite depletion, and emulsion pH in emulsions containing sulfite or EDTA.

Methods
Commercial EDTA and sulfite propofol emulsions were compared, and 10% soybean oil emulsion containing various additives were evaluated for TBARS, sulfite, and pH. TBARS were analyzed with a modified thiobarbituric acid method. Sulfite was analyzed by the reaction of sulfite with 5,5'-dithiobis(2-nitrobenzoic acid). pH was measured by glass electrode methodology.

Results
Thiobarbituric acid reacting substances were detectable in commercial sulfite propofol emulsions in concentrations ranging from 0.02 to 0.22 microg/ml based on malondialdehyde. No TBARS were detected in EDTA propofol emulsions. Incubation (37 degrees C, up to 6 h) of sulfite propofol emulsions in air resulted in further increases in TBARS (35-160%). No increases occurred in incubated EDTA propofol emulsions. Metabisulfite (0.25 mg/ml) alone added to 10% soybean oil resulted in large increases in TBARS that were inhibited in part by propofol (10 mg/ml) and completely by ascorbic acid (0.05 mg/ml). Soybean oil emulsion pH declined rapidly on the addition of metabisulfite (0.25 mg/ml). The addition of propofol (10 mg/ml) partially inhibited the decline in pH and ascorbic acid (0.05 mg/ml) completely inhibited it.

Conclusion
These results show that sulfite supports the peroxidation of lipids in soybean oil emulsions and propofol functions to partially inhibit these processes.
Mild Hypothermia Has Minimal Effects on the Tolerance to Severe Progressive Normovolemic Anemia in Swine
Authors: Perez-de-Sá Valéria , Roscher Roger , Cunha-Goncalves Doris , Larsson Anders , Werner Olof 
Published: November 2003

Background
The benefits of hypothermia during acute severe anemia are not entirely settled. The authors hypothesized that cooling would improve tolerance to anemia.

Methods
Eight normothermic (38.0 +/- 0.5 degrees C) and eight hypothermic (32.0 +/- 0.5 degrees C) pigs anesthetized with midazolam-fentanyl-vecuronium-isoflurane (0.5% inspired concentration) were subjected to stepwise normovolemic hemodilution (hematocrit, 15%, 10%, 7%, 5%, 3%). Critical hemoglobin concentration (Hgb(CRIT)) and critical oxygen delivery (DO(2CRIT)), i.e., the hemoglobin concentration (Hgb) and oxygen delivery (DO2) at which oxygen consumption (VO2, independently measured by indirect calorimetry) was no longer sustained, and Hgb at the moment of death, defined prospectively as the point when VO2, decreased below 40 ml/min, were used to assess the tolerance of the two groups to progressive isovolemic anemia.

Results
At hematocrits of 15% and 10% (Hgb, 47 and 31 g/l), VO2 was maintained in both groups by an increase (P < 0.001) in cardiac output (CO) and extraction ratio (ER; P< 0.001) with unchanged mean arterial lactate concentration (L(art)). At hematocrit of 7% (Hgb, 22 g/l), all normothermic but no hypothermic animals had DO2-dependent VO2. No normothermic and three hypothermic animals survived to 5% hematocrit (Hgb, 15 g/l), and none survived to 3%. Hgb(CRIT) was 23 +/- 2 g/l and 19 +/- 6 g/l (mean +/- SD) in normothermic and hypothermic animals, respectively (P = 0.053). Hgb at death was 19 +/- 3 g/l versus 14 +/- 4 g/l (P = 0.015), and DO(2CRIT) was 8.7 +/- 1.7 versus 4.6 +/- 0.8 ml x kg(-1) x min(-1) (P < 0.001).

Conclusion
During progressive normovolemic hemodilution in pigs, hypothermia did not significantly change Hgb(CRIT), but it decreased the Hgb at death, i.e., short-term survival was prolonged.
Influence of Hypovolemia on the Pharmacokinetics and Electroencephalographic Effect of γ-Hydroxybutyrate in the Rat
Authors: Van Sassenbroeck Diederik K. , De Paepe Peter , Belpaire Frans M. , Boon Paul A. , Buylaert Walter A. 
Published: November 2003

Background
Hypovolemia alters the effect of propofol in the rat by influencing the pharmacokinetics and the end organ sensitivity. We now studied the effect of hypovolemia on the anesthetic gamma-hydroxybutyrate (GHB) because in contrast with propofol it increases blood pressure.

Methods
Thirty-two rats were randomly assigned to undergo moderate hypovolemia or a control procedure. Each rat received either an infusion of sodium-GHB (390 mg x kg(-1) x 5 min(-1)) or the same volume of an equimolar solution of sodium chloride (6.9%). Plasma samples were taken for GHB assay (high-performance liquid chromatography) and the electroencephalography and blood pressure values were recorded. A two-compartment model with Michaelis-Menten elimination was fitted to the concentration-time data and a sigmoid E(max) model to the electroencephalographic effect effect site concentration curve allowing the study of the end organ sensitivity.

Results
Plasma concentration-time curves and the total volume of distribution in hypovolemic and normovolemic rats were comparable with only small but significant differences in central volume of distribution and the intercompartmental clearance. There was no significant difference either in the distribution from the plasma to the brain (k(e0)) or in the end organ sensitivity (EC50 = 335 +/- 76 microg/ml in control vs. 341 +/- 89 microg/ml in hypovolemic rats). GHB temporarily increased mean arterial pressure in both groups, which cannot be explained by the sodium salt alone.

Conclusions
Hypovolemia does not influence the overall concentration-time curve of GHB and induces no changes in the electroencephalographic effect of GHB in the rat. This difference with propofol may be due to the fact that it increases blood pressure but also due to its different pharmacokinetic properties.
Reactive Oxygen Species Scavengers Attenuate Endotoxin-induced Impairment of Hypoxic Pulmonary Vasoconstriction in Mice
Authors: Baboolal Hemanth A. , Ichinose Fumito , Ullrich Roman , Kawai Noriko , Bloch Kenneth D. , Zapol Warren M. 
Published: November 2003

Background
Sepsis and endotoxemia attenuate hypoxic pulmonary vasoconstriction (HPV), thereby impairing systemic oxygenation. Reactive oxygen species (ROS) are implicated in the pathogenesis of sepsis-induced lung injury. The authors investigated whether treatment with scavengers of ROS prevents impairment of HPV in mice challenged with endotoxin.

Methods
The pulmonary vasoconstrictor response to left mainstem bronchus occlusion (LMBO) was studied in anesthetized mice 22 h after an intraperitoneal challenge with saline solution or 10 mg/kg Escherichia coli endotoxin. In some mice, challenge with saline solution or endotoxin was followed after 1 h with intraperitoneal or intratracheal administration of the ROS scavengers N-acetylcysteine or EUK-8. Myeloperoxidase activity and nitric oxide synthase-2 gene expression were measured in lung tissues.

Results
The LMBO increased left pulmonary vascular resistance by 106 +/- 24% in saline-challenged control mice but by only 23 +/- 12% (P < 0.05) in endotoxin-challenged mice. Intraperitoneal administration of N-acetylcysteine or EUK-8 1 h after endotoxin challenge attenuated the endotoxin-induced impairment of HPV (58 +/- 6% and 68 +/- 10%, respectively; both P< 0.05 endotoxin-challenged mice). Intratracheal administration of ROS scavengers 1 h after endotoxin challenge was equally effective but required lower doses than systemic treatment. Administration of the ROS scavengers 22 h after endotoxin challenge did not restore HPV.

Conclusions
Administration of N-acetylcysteine or EUK-8 1 h after endotoxin challenge in mice prevented the impairment of HPV after LMBO. Early therapy with ROS scavengers, either systemically or by inhalation, may provide a means to preserve HPV in sepsis-associated acute lung injury.
Brachial Plexus Nerve Block Exhibits Prolonged Duration in the Elderly
Authors: Paqueron Xavier , Boccara Gilles , Bendahou Mouhssine , Coriat Pierre , Riou Bruno 
Published: November 2003

Background
Upper limb trauma occurs frequently in elderly patients for whom peripheral nerve blocks are often preferred for anesthesia. The characteristics of such regional blocks have, however, never been described in an elderly population. Therefore, the authors assessed prospectively the onset and duration of upper extremity peripheral nerve block (the mid-humeral block) in elderly and young patients undergoing emergency upper extremity surgery.

Methods
Consecutive patients aged > 70 yr or < 70 yr received a mid-humeral block with a small volume of ropivacaine, 0.75%. Five milliliters was injected onto each of the musculocutaneous, radial, ulnar, and median nerves. Time to complete sensory and motor block and durations of complete sensory and motor block were assessed. Results are shown as median and its 95% confidence interval.

Results
Median ages were 77 yr (95% CI, 72-81 yr) and 39 yr (95% CI, 27-46 yr) in the two groups. Both groups had similar times to complete sensory blockade. The elderly group had longer durations of complete sensory (390 min [range, 280-435 min] vs.150 min [range, 105-160 min]; P< 0.05) and motor (357 min [range, 270-475 min] vs. 150 min [range, 90-210 min]; P< 0.05) blockade. Duration of complete sensory block was significantly correlated with age (rho = 0.56; P< 0.05).

Conclusions
Age is a major determinant of duration of complete motor and sensory blockade with peripheral nerve block, perhaps reflecting increased sensitivity to conduction failure from local anesthetic agents in peripheral nerves in the elderly population.