bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of Halothane with α- and β-Adrenoceptor Stimulations in Rat Myocardium
Authors: Hanouz Jean-Luc , Riou Bruno MD , Massias Laurent , Lecarpentier Yves , Coriat Pierre 
Published: November 2003

Background
Halothane induces negative inotropic and lusitropic effects in myocardium. It has been suggested that halothane potentiates beta-adrenoceptor stimulation. However, its effects on the inotropic response to alpha-adrenoceptor stimulation and its effects on the lusitropic effects of alpha- and beta-adrenoceptor stimulation are unknown.

Methods
The effects of halothane (0.5 and 1 minimum alveolar concentration [MAC]) on the inotropic responses induced by phenylephrine (10(-8) to 10(-4) M) and isoproterenol (10(-8) to 10(-4) M) were studied in rat left ventricular papillary muscles in vitro (in Krebs-Henseleit solution at 29 degrees C, pH 7.40, with 0.5 mM calcium and stimulation frequency at 12 pulses/min). The lusitropic effects were studied in isotonic (R1) and isometric (R2) conditions.

Results
One MAC halothane induced a negative inotropic effect (54 +/- 3%, P < 0.05), increased R1 (109 +/- 3%, P < 0.05), and decreased R2 (88 +/- 2%, P < 0.05). In control groups, phenylephrine (137 +/- 7%, P > 0.05) and isoproterenol (162 +/- 6%, P < 0.05) induced a positive inotropic effect. Halothane did not significantly modify the positive inotropic effect of calcium, suggesting that it did not modify the inotropic reserve of papillary muscles. In contrast, 1 MAC halothane enhanced the positive inotropic effects of phenylephrine (237 +/- 19%, P < 0.05) and isoproterenol (205 +/- 11%, P < 0.05). Halothane did not modify the lusitropic effect of phenylephrine under high or low load. In contrast, 1 MAC halothane impaired the positive lusitropic effect of isoproterenol under low load (P < 0.05), whereas it did not modify the positive lusitropic effect of isoproterenol under high load.

Conclusions
At clinically relevant concentrations, halothane potentiated the positive inotropic effects of both alpha- and beta-adrenoceptor stimulation. Furthermore, halothane alters the positive lusitropic-effect of beta-adrenoceptor stimulation under low load.
Epidural and Intrathecal n-Butyl-p-Aminobenzoate Solution in the Rat
Authors: Grouls R. J. E. , Meert T. F. , Korsten H. H. M. , Hellebrekers L. J. , Breimer D. D. 
Published: November 2003

Background
Epidural administration of an aqueous suspension of n-butyl-p-aminobenzoate (BAB) to humans results in long-lasting sensory blockade without motor block. The dose-response of BAB administered epidurally and intrathecally as a solution was studied in rats to define the local anesthetic properties in an established animal model.

Methods
The time course of changes in tail withdrawal latency and motor function were determined in rats after epidural or intrathecal administration of solutions of BAB or bupivacaine. The dose-response relation was determined and median effective dose values were calculated.

Results
After epidural and intrathecal administration of BAB solutions, the onset and duration of the antinociceptive action were comparable to bupivacaine. Median effective dose values for tail-withdrawal latency of 6 s or more were significantly greater for BAB. After both routes of administration, BAB clearly affected motor function.

Conclusions
When administered epidurally and intrathecally as a solution, BAB is a local anesthetic of relative low potency with onset and duration of action comparable to those of bupivacaine. These findings suggest that the long-lasting action obtained after applying BAB suspension results from the slow dissolution (continuous release) of the solid BAB deposited in the epidural space.
Anesthesia-related Deaths during Obstetric Delivery in the United States, 1979–1990
Authors: Hawkins Joy L. , Koonin Lisa M. , Palmer Susan K. , Gibbs Charles P. 
Published: November 2003

Background
Anesthesia-related complications are the sixth leading cause of pregnancy-related death in the United States. This study reports characteristics of anesthesia-related deaths during obstetric delivery in the United States from 1979-1990.

Methods
Each state reports deaths that occur within 1 yr of delivery to the Centers for Disease Control and Prevention as part of the ongoing Pregnancy Mortality Surveillance. Maternal death certificates (with identifiers removed) matched with live birth or fetal death certificates when available from 1979-1990 were reviewed to identify deaths due to anesthesia, the cause of death, the procedure for delivery, and the type of anesthesia provided. Maternal mortality rates per million live births were calculated. Case fatality rates and risk ratios were computed to compare general to regional anesthesia for cesarean section deliveries.

Results
The anesthesia-related maternal mortality rate decreased from 4.3 per million live births in the first triennium (1979-1981) to 1.7 per million in the last (1988-1990). The number of deaths involving general anesthesia have remained stable, but the number of regional anesthesia-related deaths have decreased since 1984. The case-fatality risk ratio for general anesthesia was 2.3 (95% confidence interval [CI], 1.9-2.9) times that for regional anesthesia before 1985, increasing to 16.7 (95% CI, 12.9-21.8) times that after 1985.

Conclusions
Most maternal deaths due to complications of anesthesia occurred during general anesthesia for cesarean section. Regional anesthesia is not without risk, primarily because of the toxicity of local anesthetics and excessively high regional blocks. The incidence of these deaths is decreasing, however, and deaths due to general anesthesia remain stable in number and hence account for an increased proportion of total deaths. Heightened awareness of the toxicity of local anesthetics and related improvements in technique may have contributed to a reduction in complications of regional anesthesia.
Pharmacokinetics of Mivacurium Isomers and Their Metabolites in Healthy Volunteers after Intravenous Bolus Administration
Authors: Lacroix M. , Donati F. , Varin F. 
Published: November 2003

Background
Previous studies report the pharmacokinetics of mivacurium isomers after an infusion using venous blood sampling. Although the extent of the mivacurium arterial-venous gradient is not known, the sampling site is likely to influence mivacurium pharmacokinetic parameters because the drug is rapidly metabolized as it traverses the circulation. The objectives of this study were (1) to determine the pharmacokinetics of mivacurium isomers in healthy persons after intravenous bolus administration using intensive arterial blood sampling, and (2) to characterize the formation and elimination of mivacurium metabolites in human plasma.

Methods
Eight persons classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo elective surgery under balanced anesthesia received 0.15 mg/kg mivacurium chloride as an intravenous bolus. Arterial blood samples were collected every 10 s during the first 2 min and at frequent intervals for 4 h thereafter. Plasma concentrations of mivacurium isomers and their metabolites were determined by two stereoselective high-performance liquid chromatographic methods coupled with fluorometric detection and noncompartmental pharmacokinetic parameters.

Results
Mean elimination half-lives of the trans-trans, cis-trans, and cis-cis isomers were 2.4, 2, and 28.5 min, respectively, with corresponding mean plasma clearances of 29.2, 45.7, and 6.7 ml.min 1.kg-1. The volumes of distribution at steady state of the trans-trans, cis-trans, and cis-cis isomers were 0.047, 0.054, and 0.189 l/kg, respectively. Plasma concentrations of monoester and alcohol metabolites peaked 25 s (median) after mivacurium injection, with half-lives in the range of 90 min, except for the cis alcohol metabolite, which was only negligibly and transiently formed.

Conclusions
Substantial hydrolysis of mivacurium isomers by cholinesterases was confirmed by the rapid appearance of mivacurium metabolites in plasma. The intensive arterial sampling proved to be critical for the trans-trans and cis-trans isomers because the area under the curve between 0 and 2 min accounted for 75% and 86% of the total, respectively.
Inhaled Nitric Oxide Inhibits Platelet Aggregation after Pulmonary Embolism in Pigs
Authors: Gries Andre , Bottiger Bernd W. , Dorsam Joachim , Bauer Harry , Weimann Jorg , Bode Christoph , Martin Eike , Motsch Johann 
Published: November 2003

Background
Inhaled nitric oxide (NO) is reported to prolong bleeding time in animals and humans and to inhibit platelet aggregation in persons with acute respiratory distress syndrome. In pulmonary embolism (PE), inhibition of platelet aggregation appears useful because further thrombus formation may lead to right ventricular dysfunction that results in circulatory failure. In the present study, the effect of inhaled NO on platelet aggregation after acute massive PE was investigated.

Methods
After acute massive PE was induced in 25 anesthetized pigs by injecting microspheres, 5, 20, 40, and 80 parts per million inhaled NO were administered stepwise for 10 min each in 11 animals (NO group). In the control group (n = 14). NO was not administered. Adenosine diphosphate-induced initial and maximal platelet aggregation were measured before PE (10), immediately after induction of PE (PE), at the end of each 10-min NO inhalation interval (t10-t40), and 15 min after cessation of NO inhalation (t55) in the NO group, and at corresponding times in the control group, respectively.

Results
Two animals in the control group and one in the NO group died within 10 min after PE induction and were excluded from analysis. Peaking at t40 and t55, respectively, initial (-13 +/- 6%; P < 0.05) and maximal (+44 +/- 17%; P < 0.05) platelet aggregation increased significantly after PE in the control group. In contrast, NO administration after PE led to a significant decrease in initial (maximum decrease, -9 +/- 3% at t40; P < 0.05) and maximal (maximum decrease, -15 +/- 7% at t30; P < 0.05) platelet aggregation. In the NO group, platelet aggregation had returned to baseline levels again at t55. In addition, NO administration significantly decreased mean pulmonary artery pressure and significantly increased end-tidal carbon dioxide concentration and mean systemic blood pressure.

Conclusions
Inhaled NO has a systemic and rapidly reversible inhibitory effect on platelet aggregation after acute massive PE in pigs. This may be beneficial in treating acute massive PE.
Blocking Mechanisms of Ketamine and Its Enantiomers in Enzymatically Demyelinated Peripheral Nerve as Revealed by Single-channel Experiments
Authors: Brau Michael E. , Sander Frank , Vogel Werner , Hempelmann Gunter 
Published: November 2003

Background
Ketamine shows, besides its general anesthetic effect, a local anesthetic-like action that is due to blocking of peripheral nerve sodium currents. In this study, the stereoselectivity of the blocking effects of the ketamine enantiomers S(+) and R(-) was investigated in sodium and potassium channels in peripheral nerve membranes.

Methods
Ion channel blockade of ketamine was investigated in enzymatically dissociated Xenopus sciatic nerves in multiple-channel and in single-channel outside-out patches.

Results
Concentration-effect curves for the Na+ peak current revealed half-maximal inhibiting concentrations (IC50) of 347 microM and 291 microM for S(+) and R(-) ketamine, respectively. The potential-dependent K+ current was less sensitive than the Na+ current with IC50 values of 982 microM and 942 microM. The most sensitive ion channel was the flickering background K+ channel, with IC50 values of 168 microM and 146 microM for S(+) and R(-) ketamine. Competition experiments suggest one binding site at the flicker K+ channel, with specific binding affinities for each of the enantiomers. For the Na+ channel, the block was weaker in acidic (pH = 6.6) than in neutral (pH = 7.4) and basic (pH = 8.2) solutions; for the flicker K+ channel, the block was weaker in acidic and stronger in basic solutions.

Conclusions
Ketamine blockade of sodium and potassium channels in peripheral nerve membranes shows no stereoselectivity except for the flicker K+ channel, which showed a very weak stereoselectivity in favor of the R(-) form. This potential-insensitive flicker K+ channel may contribute to the resting potential. Block of this channel and subsequent depolarization of the resting membrane potential leads, besides to direct Na+ channel block, to inexcitability via Na+ channel inactivation.
Ascorbic Acid Inhibits Spinal Meningeal Catechol-o-Methyl Transferase in Vitro, Markedly Increasing Epinephrine Bioavailability
Authors: Kern C. , Bernards C. M. 
Published: November 2003

Background
The spinal menings have previously been shown to contain catechol-o-methyl transferase (COMT), the enzyme that metabolizes epinephrine to the inactive metabolite metanephrine. The authors of this study aimed to quantitate the metabolism of epinephrine traversing the spinal meninges and to determine if that metabolism could be inhibited. In addition, they tried to determine the meningeal permeability of epinephrine.

Methods
Macca nemestrina spinal meninges were mounted in a diffusion cell and epinephrine was added to the donor reservoir at time 0. Three hundred minutes later, all buffer in the recipient reservoir was collected and analyzed for epinephrine metabolites. The experiments were conducted with either ascorbic acid (1 mM) or sodium metabisulfite (5.3 mM) added as antioxidants.

Results
In the presence of sodium metabisulfite, 60 +/- 6% of the epinephrine traversing the meningeal specimens was metabolized by COMT. In contrast, in the presence of ascorbic acid, less than 3% of the epinephrine traversing the spinal meninges was metabolized by COMT (P = 0.0001). The meningeal permeability coefficient for epinephrine was 0.38 +/- 0.08 cm/min x 10(-3).

Conclusions
Epinephrine permeability through the spinal meninges is low, and meningeal COMT markedly reduces the bioavailability of what little epinephrine can traverse the meninges. However, a clinically relevant concentration of ascorbic acid, a competitive inhibitor of COMT, almost completely blocks epinephrine metabolism and increases the bioavailability of epinephrine.
How Much Oxygen Does the Human Lung Consume?
Authors: Loer Stephan A. , Scheeren Thomas W. L. , Tarnow Jorg 
Published: November 2003

Background
The amount of oxygen consumed by the lung itself is difficult to measure because it is included in whole-body gas exchange. It may be increased markedly under pathological conditions such as lung infection or adult respiratory distress syndrome. To estimate normal oxygen consumption of the human lung as a basis for further studies, respiratory gas analysis during total cardiopulmonary bypass may be a simple approach because the pulmonary circulation is separated from systemic blood flow during this period.

Methods
Lung oxygen consumption was determined in 16 patients undergoing cardiac surgery. During total cardiopulmonary bypass their lungs were ventilated with low minute volumes (tidal volume, 150 ml; rate, 6 min-1; inspiratory oxygen fraction, 0.5; positive end-expiratory pressure, 3 mmHg). All expiratory gas was collected and analyzed by indirect calorimetry. As a reference value also, whole-body oxygen consumption of these patients was determined before total cardiopulmonary bypass. In a pilot study of eight additional patients (same ventilatory pattern), the contribution of systemic (bronchial) blood flow to pulmonary gas exchange during cardiopulmonary bypass was assessed. For this purpose, the amount of enflurance diffusing from the systemic blood into the bronchial system was measured.

Results
The human lung consumes about 5-6 ml oxygen per minute at an esophageal temperature of 28 degrees C. Prebypass whole-body oxygen consumption measured at nearly normothermic conditions was 198 +/- 28 ml/min. Mean lung and whole-body respiratory quotients were similar (0.84 and 0.77, respectively). Extrapolating lung oxygen consumption to 36 degrees C suggests that the lung consumes about 11 ml/min or about 5% of total body oxygen consumption. Because the amount of enflurane diffused from the systemic circulation into the bronchial system during cardiopulmonary bypass was less than 0.1%, the contribution of bronchial blood flow to lung gas exchange can be assumed to be negligible.

Conclusions
The lung consumes about 5% of whole-body oxygen uptake.
Pharmacodynamic Modeling of Vecuronium-induced Twitch Depression
Authors: Fisher Dennis M. , Szenohradszky Janos , Wright Peter M. C. , Lau Marie , Brown Ronald , Sharma Manohar 
Published: November 2003

Background
After bolus doses of nondepolarizing muscle relaxants, the adductor pollicis recovers from paralysis more slowly than the diaphragm and the laryngeal adductors, suggesting that the adductor pollicis is more sensitive than the respiratory muscles to effects of those drugs. In contrast, during onset, the respiratory muscles are paralyzed more rapidly than the adductor pollicis, suggesting that the respiratory muscles are more sensitive than the adductor pollicis. To reconcile these apparently conflicting findings, we determined vecuronium's pharmacokinetics and its pharmacodynamics at both the adductor pollicis and the laryngeal adductors.

Methods
Six volunteers were studied on two occasions during anesthesia with propofol. Mechanical responses to train-of-four stimulation were measured at the adductor pollicis and at the laryngeal adductors. Vecuronium (15-60 micrograms/kg) was given and arterial plasma samples were obtained from 0.5-60 min. Vecuronium doses differed by twofold on the two occasions. A pharmacokinetic model accounting for the presence and potency of vecuronium's 3-desacetyl metabolite and a sigmoid e-max pharmacodynamic model were fit to the resulting plasma concentration and effect (adductor pollicis and laryngeal adductors) data to determine relative sensitivities and rates of equilibration between plasma and effect site concentrations.

Results
The steady-state plasma concentration depressing laryngeal adductor twitch tension by 50% was approximately 1.5 times larger than that for the adductor pollicis. The equilibration rate constant between plasma and laryngeal adductor concentrations was about 1.5 faster than that between plasma and adductor pollicis concentrations. The Hill factor (gamma) that describes the steepness of the laryngeal adductor concentration-effect relation was approximately 0.6 times that of the adductor pollicis.

Conclusions
More rapid equilibration between plasma and laryngeal adductor vecuronium concentrations explains why onset is more rapid at the laryngeal adductors than at the adductor pollicis. During recovery, both rapid equilibration and lesser sensitivity of the laryngeal adductors contribute to earlier recovery.
Are Plasma Concentration Values Necessary for Pharmacodynamic Modeling of Muscle Relaxants?
Authors: Fisher Dennis M. , Wright Peter M. C. 
Published: November 2003

Background
The traditional approach to pharmacokinetic/ pharmacodynamic modeling of muscle relaxants requires sampling of plasma to determine drug concentrations. The authors recently proposed that certain pharmacodynamic characteristics (IR50, the steady-state infusion rate to maintain 50% twitch depression; keo, the rate constant for equilibration between plasma concentration and effect; and gamma, the Hill factor describing sigmoidicity of the concentration-effect relation) could be estimated without plasma concentration data. Here estimates for IR50, keo, and gamma determined with and without plasma concentration data are compared.

Methods
Six volunteers were given 15-60 micrograms/kg vecuronium on each of two occasions during anesthesia with propofol. Mechanical responses to train-of-four stimulation were measured at the adductor pollicis and at the laryngeal adductors. Various pharmacokinetic models accounting for the presence and potency of vecuronium's 3-desacetyl metabolite and a sigmoid e-max pharmacodynamic model were fit to the resulting plasma concentration and effect (adductor pollicis and laryngeal adductors) data to determine IR50 keo, and gamma for each effect. One model related dose to effect without plasma concentration data.

Results
Values for IR50(adductor pollicis), IR50(laryngeal adductors), gamma (adductor pollicis), and gamma (laryngeal adductors) were similar when determined with and without plasma concentration values. Values for keo (adductor pollicis) and keo (laryngeal adductors) were larger when determined without plasma concentration values compared with those determined with these values; however, the ratio of keo (adductor pollicis) to keo(laryngeal adductors) was similar when determined with and without plasma concentration values.

Conclusions
Certain pharmacodynamic parameters were estimated accurately in the absence of plasma concentration values. This suggests limited utility for plasma concentration data under conditions similar to those of the present study.
Association between Latex Sensitization and Repeated Latex Exposure in Children
Authors: Porri F. , Pradal M. , Lemiere C. , Birnbaum J. , Mege J. L. , Lanteaume A. , Charpin D. , Vervloet D. , Camboulives J. 
Published: November 2003

Background
Children with spina bifida are at greater risk for latex and ethylene oxide sensitization. The authors' aim in this study was to evaluate the role of previous surgical procedures in the development of sensitization to latex and ethylene oxide.

Methods
The authors investigated 80 children 1-16 yr old, separated into 3 groups. Two groups had a history of 3 or more general anesthetics: 29 children had spina bifida (spina bifida group) and 31 had undergone multiple surgeries for another disease (multiple surgeries group). A control group of 20 children had undergone less than 1 anesthetic. Clinical manifestations with latex, perioperative anaphylactic reactions, and number of previous anesthetics were recorded. Skin prick tests with a commercial extract of latex, four common inhalant allergens, and radioallergosorbent test to latex and ethylene oxide were performed.

Results
The three groups did not differ significantly with respect to age, sex, and atopic status. Mean number of anesthetics was comparable in the spina bifida and the multiple surgeries group. Latex sensitization was common in the spina bifida group (59%) and in the multiple surgeries group (55%) but not in the control group (0%, P < 0.05). Ethylene oxide sensitization was significantly more frequent in the spina bifida group than in the multiple surgeries group (44% vs. 19%; P = 0.052) and strongly associated with latex sensitization. Mean number of previous anesthetics was greater in children sensitized to latex (8.4 vs. 3.9; P < 0.05).

Conclusion
Results suggest that it is the number of surgical procedures rather than spina bifida per se that is related to sensitization to latex.