bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Inorganic Fluoride Concentrations after Sevoflurane Anesthesia in Children
Authors: Levine M. F. , Sarner J. , Lerman J. , Davis P. , Sikich N. , Maloney K. , Motoyama E. , Cook D. R. 
Published: November 2003

Background
Sevoflurane is degraded in vivo in adults yielding plasma concentrations of inorganic fluoride [F-] that, in some patients, approach or exceed the 50- micron theoretical threshold for nephrotoxicity. To determine whether the plasma concentration of inorganic fluoride [F-] after 1-5 MAC x h sevoflurane approaches a similar concentration in children, the following study in 120 children scheduled for elective surgery was undertaken.

Methods
Children were randomly assigned to one of three treatment groups before induction of anesthesia: group 1 received sevoflurane in air/oxygen 30% (n = 40), group 2 received sevoflurane in 70% N2O/30% O2 (n = 40), and group 3 received halothane in 70% N2O/30% O2 (n = 40). Mapleson D or F circuits with fresh gas flows between 3 and 61/min were used Whole blood was collected at induction and termination of anesthesia and at 1, 4, 6, 12, and 18 or 24 h postoperatively for determination of the [F-]. Plasma urea and creatinine concentrations were determined at induction of anesthesia and 18 or 24 h postoperatively.

Results
The mean (+/- SD) duration of sevoflurane anesthesia, 2.7 +/- 1.6 MAC x h (range 1.1-8.9 MAC x h), was similar to that of halothane, 2.5 +/- 1.1 MAC x h. The peak [F-] after sevoflurane was recorded at 1 h after termination of the anesthetic in all but three children (whose peak values were recorded between 4 and 6 h postanesthesia). The mean peak [F-] after sevoflurane was 15.8 +/- 4.6 microns. The [F-] decreased to <6.2 microns b 24 h postanesthesia. Both the peak [F-] (r2 = 0.50) and the area under the plasma concentration of inorganic fluoride-time curve (r2 = 0.57) increased in parallel with the MAC x h of sevoflurane. The peak [F-] after halothane, 2.0 +/- 1.2 microns, was significantly less than that after sevoflurane (P<0.00012) and did not correlate with the duration of halothane anesthesia (MAC x h; r2 = 0.007). Plasma urea concentrations decreased 24 h after surgery compared with preoperative values for both anesthetics (P<0.01), whereas plasma creatinine concentrations did not change significantly with either anesthetic.

Conclusions
It was concluded that, during the 24 h after 2.7 +/- 1.6 MAC x h sevoflurane, the peak recorded [F-] is low (15.8 microns), F- is eliminated rapidly, and children are unlikely to be at risk of nephrotoxicity from high [F-].
Isoflurane and Sevoflurane Modulate Inactivation Kinetics of Calcium sup 2+ Currents in Single Bullfrog Atrial Myocytes
Authors: Hirota Koki , Fujimura Junko , Wakasugi Masahiro , Ito Yusuke 
Published: November 2003

Background
To clarify the mechanism(s) of anesthetic depression of myocardial Ca2+ currents, the effects of isoflurane and sevoflurane on the inactivation kinetics of Ca2+ current in single bullfrog atrial myocytes were studied.

Methods
Freshly isolated bullfrog atrial myocytes were obtained with an enzymatic dispersion procedure. Ca2+ currents were recorded with a whole-cell voltage-clamp technique.

Results
Both isoflurane (1.25, 2.5, 5.0 vol%) and sevoflurane (2.5, 5.0 vol%) decreased the peak amplitude of Ca2+ current ICa with a minimal change in the time to peak and the reversal potential. The inactivation kinetics studies revealed that (1) isoflurane (2.5 vol%) and sevoflurane (5.0 vol%) markedly reduced the time constant of inactivation in ICa to 55% and 75% of control, respectively; (2) isoflurane (2.5 vol%) shifted the midpoint (V1/2) of steady-state inactivation curve of ICa toward negative by 2.3 mV; and (3) isoflurane (2.5 vol%) delayed the reactivation time constant of ICa to 119% of control. The further computer-simulation study demonstrated that the observed decrease of time constant by isoflurane (1.25, 2.5 vol%) and sevoflurane (2.5 vol%) can explain the reduction in amplitude of ICa.

Conclusions
The depression of ICa by lower concentration of isoflurane (1.25, 2.5 vol%) and sevoflurane (2.5 vol%) mainly is due to the decrease of time constant and, at higher concentration, isoflurane and sevoflurane may affect the other membrane components.
Prolonged d-Tubocurarine Infusion and/or Immobilization Cause Upregulation of Acetylcholine Receptors and Hyperkalemia to Succinylcholine in Rats
Authors: Yanez P. , Martyn J. A. J. 
Published: November 2003

Background
Hyperkalemic cardiac arrest after the administration of succinylcholine (SCh) to critically ill intensive care patients has been attributed to changes in the acetylcholine receptors (AChRs) at the muscle membrane. The current study attempts to characterize the contributory roles of chronic administration of nondepolarizing muscle relaxants typified by d-tubocurarine (dTC) and/or of immobilization on AChR upregulation and the relationship of these AChR changes to SCh-induced hyperkalemia.

Methods
Rats received chronic subparalytic infusion of saline or dTC for 28 days via subcutaneous osmotic pumps inserted while they were under anesthesia. Approximately half of the saline- or dTC-treated rats underwent bilateral hind-limb immobilization with plaster casts for the same duration as the infusion. After 4 weeks, the osmotic pumps were removed, and 24-48 h later, the blood potassium concentrations were measured at baseline and at 1, 3, 5, 7, and 10 min after SCh (3 mg/kg). At the end of this period, the gastrocnemius muscle was excised for quantitation of AChR number using (125)I-alpha-bungarotoxin.

Results
At 28 days, the weight gain in mobile animals receiving saline or dTC infusion did not differ, nor did that in immobilized animals receiving saline or dTC infusion, confirming that infusion of dTC did not unduly affect the ability of the animals to feed. The maximal potassium change after SCh occurred at 5 min. Potassium responses to SCh changed (mean +/- SE): (1) from 3.9 +/- 0.04 to 4.5 +/- 0.1 mEq/1 in the mobile saline- treated control group, where the AChR concentration was 18.4 +/- 2 fmol/mg protein; (2) from 3.9 +/- 0.03 to 5.1 +/- 0.1 in the mobile dTC-infused group (AChRs = 48.6 +/- 7); (3) from 3.8 +/- 0.1 to 5.5 +/- 0.3 in the immobilized saline- treated group (AChRs = 107.4 +/- 14); and (4) from 3.8 +/- 0.1 to 6.3 +/- 0.2 in the immobilized-dTC-treated group (AChRs = 183.5 +/- 23). There was a significant positive correlation between maximal change in blood potassium concentration and the respective AChR concentration in the gastrocnemius of the same animal (r = 0.81, P<0.01).

Conclusions
Subtherapeutic (subparalytic) doses of chronic infusion of dTC (with no immobilization) or immobilization alone (with no dTC) independently increased number of AChRs. The infusion of dTC with immobilization caused the greatest upregulation of AChRs. The magnitude of the increase in blood potassium to SCh was directly dependent on AChR number. This study shows direct evidence and confirms previous speculation that AChR number plays an important role in the magnitude of the hyperkalemic response to SCh. Presuming this represents an appropriate model for patients who are immobilized and/or receiving nondepolarizing muscle relaxants for prolonged periods, exaggerated blood potassium responses to SCh are possible when either or both of these perturbations are present in patients.
Palmitoyl Carnitine Increases the Transmeningeal Flux of Hydrophilic but Not Hydrophobic Compounds In Vitro
Authors: Bernards Christopher M. , Kern Christian 
Published: November 2003

Background
Increasing drug penetration through the spinal meninges should improve epidural analgesia/anesthesia by increasing the rate and extent to which epidurally administered drugs redistribute to the spinal cord. Palmitoyl carnitine has been shown to improve drug penetration through the intestinal mucosa. The purpose of this study was to determine whether palmitoyl carnitine improves drug penetration through the spinal meninges.

Methods
The transmeningeal flux of morphine, mannitol, bupivacaine, and sufentanil was determined through the spinal meninges of Macacca nemestrina monkeys before and after addition of palmitoyl carnitine. Flux was determined using a previously established in vitro diffusion cell method.

Results
Palmitoyl carnitine significantly increased the transmeningeal flux of mannitol, morphine, and bupivacaine by 942 +/- 102%, 401 +/- 43%, and 12 +/- 4%, respectively. However, palmitoyl carnitine had no significant effect on the transmeningeal flux of sufentanil. The penetration-enhancing effect of palmitoyl carnitine was shown to depend on the dose of palmitoyl carnitine added and on the octanol:buffer distribution coefficient of the study drugs but not on the concentration of the study drug.

Conclusions
The mechanism by which palmitoyl carnitine increases transmeningeal flux is unclear but may be a result of palmitoyl carnitine's ability to decrease packing order of lipid bilayers in the arachnoid mater cell membranes. Regardless of the mechanism, palmitoyl carnitine's ability to selectively increase the transmeningeal flux of hydrophilic compounds in vitro offers the possibility of improving the spinal bioavailability of this group of epidurally administered drugs in vivo.
Attenuated Hypoxic Pulmonary Vasoconstriction during Isoflurane Anesthesia Is Abolished by Cyclooxygenase Inhibition in Chronically Instrumented Dogs
Authors: Lennon Paul F. , Murray Paul A. 
Published: November 2003

Background
Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism whereby gas exchange is improved through the diversion of blood flow away from poorly oxygenated regions of the lung. The effect of isoflurane anesthesia on HPV is unclear. Using a chronically instrumented canine model, it was hypothesized that isoflurane anesthesia would attenuate HPV compared to the response measured in the same animal in the conscious state. Moreover, because volatile anesthetics increase the production of cyclooxygenase metabolites, it was hypothesized that attenuation of HPV during isoflurane anesthesia would be abolished by cyclooxygenase inhibition.

Methods
Left pulmonary vascular pressure-flow plots were generated in chronically instrumented dose by measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during inflation of a hydraulic occluder implanted around the right main pulmonary artery. In protocol 1 (n - 7), left pulmonary vascular pressure-flow plots were generated during normoxia and hypoxia (systemic arterial PO2 approximately 50 mmHg) in the conscious and isoflurane-anesthetized states. In protocol 2 (n = 7), left pulmonary vascular pressure-flow plots were generated during normoxia and hypoxia (1) in the conscious state, (2) in the conscious state after inhibition of the cyclooxygenase pathway with indomethacin, and (3) during isoflurane anesthesia after cyclooxygenase inhibition.

Results
In both the conscious and isoflurane-anesthetized states, the magnitude of HPV was dependent on the level of left pulmonary blood flow. Compared to the response measured in the conscious state, the magnitude of HPV was attenuated during isoflurane anesthesia over the empirically measured range of left pulmonary blood flow. Cyclooxygenase inhibition abolished the isoflurane-induced attenuation of HPV.

Conclusions
This is the first study to demonstrate that isoflurane anesthesia attenuates the magnitude of HPV compared to the response measured in the same animal in the conscious state. Cyclooxygenase inhibition potentiated the magnitude of HPV in both the conscious and isoflurane-anesthetized states, which indicates that vasodilator metabolites of the cyclooxygenase pathways modulate HPV under these conditions. Importantly, the finding that the magnitude of HPV is flow-dependent in both the conscious and isoflurane-anesthetized states may explain conflicting reports in the literature concerning the effects of isoflurane anesthesia on the HPV response.
Quantitation of Depth of Thiopental Anesthesia in the Rat
Authors: Gustafsson Lars L. , Ebling William F. , Osaki Eileen , Stanski Donald R. 
Published: November 2003

Background
In contrast to that of inhalational anesthetics, quantitation of anesthetic depth for intravenous agents has not been well defined. In this study, using rodents, the relationship between the constant plasma thiopental concentrations and the clinical response to multiple nociceptive stimuli were investigated characterizing the anesthetic state from light sedation to deep anesthesia and correlated to the degree of electroencephalogram (EEG) drug effect.

Methods
Thirty rats were instrumented with chronically implanted EEG electrodes, arterial and venous catheters. A computer-driven infusion pump was used to rapidly attain and then maintain constant, target plasma thiopental concentrations ranging from 7 to 100 micrograms/ml. Three different target plasma thiopental concentrations were achieved in each rat. Electroencephalographic effects were monitored with aperiodic waveform analysis. The following nociceptive stimuli were applied: (1) unprovoked righting reflex, (2) provoked righting reflex, (3) noise stimulus, (4) tail clamping with an alligator clip, (5) constant tail pressure with an analgesiameter, (6) corneal reflex, and (7) tracheal intubation. For tail clamping, tail pressure, and intubation, either purposeful extremity movement or abdominal muscle contraction response was noted to be present or absent. The clinical responses (present or absent) were modeled using logistic regression to estimate the Cp50, the plasma thiopental concentration with a 50% probability of no response.

Results
The following mean Cp50 values (95% confidence interval) were obtained: unprovoked righting reflex, 15.9 (15.1-16.6) micrograms/ml; provoked righting reflex, 21.4 (20.2-22.7) micrograms/ml; noise stimuli, 31.3 (29.7-33.0) micrograms/ml; tail clamp and limb movement, 38.3 (36.1-40.4) micrograms/ml; tail pressure and limb movement, 39.2 (37.1-41.3) micrograms/ml; tail pressure and abdominal muscle contraction, 52.5 (50.0- 55) micrograms/ml; tail clamping and abdominal muscle contraction, 56.1 (50.0-56.2) micrograms/ml; corneal reflex, 60.0 (56.6-63.4) micrograms/ml; and limb movement or muscle abdominal contraction response to intubation, 67.7 (59.2-76.1) micrograms/ml. At an EEG-effect of 9.1 and 2.2 waves/s, there was a 50% chance of limb movement response to tail clamping and tracheal intubation, respectively. There was a poor relationship between the plasma thiopental concentration and the percent increase of either heart rate or mean arterial blood pressure after applying either tail pressure or tail clamp stimuli.

Conclusions
A range of nociceptive stimuli and their observed clinical responses can be used to quantitate thiopental anesthetic depth, ranging from light sedation to deep anesthesia (isoelectric EEG and unresponsive to intubation) in the rodent. Clinical response can be mapped to surrogate EEG measures.
Fluoride Ion Toxicity in Human Kidney Collecting Duct Cells
Authors: Cittanova Marie-Laure , Lelongt Brigitte , Verpont Marie-Christine , Geniteau-Legendre Monique , Wahbe Fayez , Prie Dominique , Coriat Pierre , Ronco Pierre M. 
Published: November 2003

Background
Several halogenated anesthetics induce a urinary concentrating defect, partly related to fluoride ion toxicity in collecting duct cells. The aim of this study was to investigate the effects of fluoride ion in human kidney cells.

Methods
Immortalized human collecting duct cells were used. In a first set of experiments, the toxicity threshold concentration was determined by exposing cell cultures for 24 h to increasing concentrations of fluoride ion in the medium: 0, 1, 5, and 10 mM. The second set of experiments was a time- effect study in which cells were exposed to 5 mM fluoride for 2, 6, and 24 h. Assessment of toxicity was based on several endpoints: cell number, protein content, (3)H-leucine incorporation in newly synthesized proteins, extracellularly released lactate dehydrogenase, Na-K-ATPase pump activity, and electron microscope studies.

Results
After 24 h of exposure, fluoride ion decreased cell number (-23%, P<0.05), total protein content (-30%, P<0.05) and increased lactate dehydrogenase release (+236%, P<0.05) at a threshold concentration of 5mM. Fluoride ion also inhibited Na-K- ATPase activity at 5 mM (-58%, P<0.05). Major morphologic alterations of mitochondria, including crystal formation, were detected from 1 mM fluoride concentration. Time-effect studies showed that, after only 6 h of exposure at 5 mM, fluoride decreased cell number (-13%, P<0.05), (3)H-leucine incorporation (-48%, P<0.05), and Na-K-ATPase activity (- 20%, P<0.05) and increased lactate dehydrogenase release (+145%, P<0.05). Crystal deposits in mitochondria again were a more sensitive marker of cell injury, detectable after only 2 h of exposure.

Conclusions
these results suggest that the mitochondrion is a target of fluoride toxicity in human collecting duct cells, and its alteration is partly responsible for the sodium and water disturbances observed in patients.
Effect of Epidural Analgesia on Fundal Dominance during Spontaneous Active-Phase Nulliparous Labor
Authors: Nielsen Peter E. , Abouleish Ezzat , Meyer Bruce A. , Parisi Valerie M. 
Published: November 2003

Background
The purpose of this investigation was to determine if epidural analgesia, established during active phase labor, results in elimination or reversal of fundal dominance (lower uterine segment pressure equal to or greater than fundal pressure).

Methods
Upper and lower uterine segment intrauterine pressures were prospectively evaluated for 50 min before and 50 min after epidural analgesia using 0.25% bupivacaine in 11 nulliparous women in spontaneous active labor. A total of 958 contractions were evaluated.

Results
No significant differences were found in the number of contractions in the interval before epidural analgesia compared to after epidural analgesia. Significantly greater pressure readings were recorded in the upper segment than in the lower segment (consistent with fundal dominance) both before and after epidural analgesia (P<0.01). In addition, fundal dominance increased after epidural analgesia when compared to the preanalgesia period (P<0.01).

Conclusions
Fundal dominance is present both before and after active phase epidural analgesia and is increased during the immediate 50-min postanalgesia period.
Preservation of the Ratio of Cerebral Blood Flow/Metabolic Rate for Oxygen during Prolonged Anesthesia with Isoflurane, Sevoflurane, and Halothane in Humans
Authors: Kuroda Yasuhiro , Murakami Mari , Tsuruta Junko , Murakawa Toshisuke 
Published: November 2003

Background
In several animal studies, an increase in cerebral blood flow (CBF) produced by volatile anesthetics has been reported to resolve over time during prolonged anesthesia. It is important to investigate whether this time-dependent change of CBF takes place in humans, especially in clinical situations where surgery is ongoing under anesthesia. In this study, to evaluate the effect of prolonged exposure to volatile anesthetics (isoflurane, sevoflurane, and halothane), the CBF equivalent (CBF divided by cerebral metabolic rate for oxygen (CMRO2) was determined every 20 min during anesthesia lasting more than 4h in patients.

Methods
Twenty-four surgical patients were assigned to three groups at random to receive isoflurane, sevoflurane, or halothane (8 patients each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 MAC before surgery and then 1.5 MAC for the 3 h of surgical procedure. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 60 mmHg, using phenylephrine infusion, if necessary. CBF equivalent was calculated every 20 min as the reciprocal of arterial-jugular venous oxygen content difference.

Results
CBF equivalent at 0.5 MAC of isoflurane, halothane, and sevoflurane was 21 +/- 4, 20 +/- 3, and 21 +/- 5 ml blood/ml oxygen, respectively. All three examined volatile anesthetics significantly (P<0.01) increased CBF equivalent in a dose-dependent manner (0.5, 1.0, 1.5 MAC). AT 1.5 MAC, the increase of CBF equivalent with all anesthetics was maintained increased with minimal fluctuation for 3 h. The mean value of CBF equivalent at 1.5 MAC in the isoflurane group (45 +/- 8) was significantly (P<0.01) greater than those in the halothane (32 +/- 8) and sevoflurane (31 +/- 8) groups. Electroencephalogram was found to be relatively unchanged during observation periods at 1.5 MAC.

Conclusions
These results demonstrate that CBF/CMRO2 ratio is markedly increased above normal and maintained during prolonged inhalation of volatile anesthetics in humans. It is impossible to determine whether these data indicate a stable CBF or whether CBF and CMRO2 are changing in parallel during the observation period. The unchanging electroencephalographic pattern suggests that the former possibility is more likely and that the increase of CBF produced by volatile anesthetics is maintained over time without decay, which has been reported in several animal studies. It also is suggested that isoflurane possesses greater capability to maintain global CBF relative to CMRO(2) than does halothane or sevoflurane. time.)
Mivacurium When Precedent by Pancuronium Becomes a Long-acting Muscle Relaxant
Authors: Erkola Olli , Rautoma Pekka , Meretoja Olli A. 
Published: November 2003

Background
To ensure rapid recovery of neuromuscular block, it might be useful to administer a short-acting relaxant after a long-acting one. Therefore, the interaction between pancuronium and mivacurium was investigated when mivacurium was administered during the recovery from pancuronium block.

Methods
After written informed consent, 41 adult patients were studied during propofol/alfentanil/nitrous oxide/oxygen anesthesia. Neuromuscular function was monitored using an electromyographic (EMG) method. AFter a stable EMG calibration response, cumulative doses of pancuronium were given to establish a 95% neuromuscular block. In the control group, and ED95 dose of 100 microg/kg mivacurium was administered instead of pancuronium. When the EMG response after pancuronium or mivacurium had recovered to 25% of the baseline, a single randomized intravenous bolus dose of 10 or 70 microg/kg mivacurium was given. Thereafter, spontaneous recovery of the neuromuscular function was recorded.

Results
The time from pancuronium until T1 25% EMG recovery was 38 +/- 12 min (mean +/- SD). The respective times after 10 or 70 microg/kg mivacurium were 28 +/- 8 and 54 +/- 7 min in the pancuronium group or 3 +/- 1 (n=3) and 10 +/- 4 min in the mivacurium group (P=0.0001). Times to 95% EMG recovery after 10 or 70 microgm/kg mivacurium were 77 +/- 14 and 97 +/- 16 min in the pancuronium group and 11 +/- 3 and 20 +/- 7 min in the mivacurium group, respectively (P<0.0001). Recovery indexes after 10 or 70 microg/kg mivacurium group, respectively (P<0.0001). Recovery indexes after 10 or 70 microg/kg mivacurium wre 26 +/- 4 and 22 +/- 6 min in the pancuronium group or 7 +/- 3 (n=3) and 5+/- 2 min in the mivacurium group, respectively (P<0.0001). Times from the administration of 10 or 70 microg/kg mivacurium until train-of-four ration 0.7 were 94 +/- 16 and 111 +/- 14 min in the pancuronium group and 12 +/- 4 and 22 +/- 8 min in the mivacurium group, respectively (P<0.0001).

Conclusions
After pancuronium, mivacurium is not a short acting neuromusclar blocking agent.