bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preservation of Hypoxic Pulmonary Vasoconstriction during Sevoflurane and Desflurane Anesthesia Compared to the Conscious State in Chronically Instrumented Dogs
Authors: Lesitsky Marc A. , Davis Steve , Murray Paul A. 
Published: November 2003

Background
The authors' objective was to assess the extent to which sevoflurane and desflurane anesthesia alter the magnitude of hypoxic pulmonary vasoconstriction compared with the response measured in the same animal in the conscious state.

Methods
Left pulmonary vascular pressure-flow plots were generated in seven chronically instrumented dogs by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. Pressure-flow plots were generated during normoxia and hypoxia on separate days in the conscious state, during sevoflurane (approximately 3.5% end-tidal), and during desflurane (approximately 10.5% end-tidal) anesthesia. Values are mean+/-SEM.

Results
In the conscious state, administration of the hypoxic gas mixture by conical face mask decreased (P < 0.01) systemic arterial PO2 from 94+/-2 mmHg to 50+/-1 mmHg and caused a leftward shift (P < 0.01) in the pressure-flow relationship, indicating pulmonary vasoconstriction. The magnitude of hypoxic pulmonary vasoconstriction in the conscious state was flow-dependent (P < 0.01). Neither anesthetic had an effect on the baseline pressure-flow relationship during normoxia. The magnitude of hypoxic pulmonary vasoconstriction during sevoflurane and desflurane was also flow-dependent (P < 0.01). Moreover, at any given value of flow the magnitude of hypoxic pulmonary vasoconstriction was similar during sevoflurane and desflurane compared with the conscious state.

Conclusion
These results indicate that hypoxic pulmonary vasoconstriction is preserved during sevoflurane and desflurane anesthesia compared with the conscious state. Thus, inhibition of hypoxic pulmonary vasoconstriction is not a general characteristic of inhalational anesthetics. The flow-dependent nature of the response should be considered when assessing the effects of physiologic or pharmacologic interventions on the magnitude of hypoxic pulmonary vasoconstriction.
Common Genetic Determinants of Halothane and Isoflurane Potencies in Caenorhabditis elegans
Authors: van Swinderen Bruno , Galifianakis Alex , Crowder Michael C. 
Published: November 2003

Background
Genetics provides a way to evaluate anesthetic action simultaneously at the molecular and behavioral levels. Results from strains that differ in anesthetic sensitivity have been mixed in their support of unitary theories of anesthesia. Here the authors use the previously demonstrated large variation of halothane sensitivities in Caenorhabditis elegans recombinant inbred strains to assess the similarities of the determinants of halothane action with those of another volatile anesthetic, isoflurane.

Methods
The recombinant inbred strains, constructed from two evolutionarily distinct C. elegans lineages, were phenotyped. A coordination assay on agar quantified the sensitivity to the volatile anesthetics; median effective concentrations (EC50s) were calculated by nonlinear regression of concentration-response data and were correlated between the drugs for those strains tested in common. Genetic loci were identified by statistical association between EC50s and chromosomal markers.

Results
The recombinant inbred strains varied dramatically in sensitivity to halothane and isoflurane, with a 10-fold range in EC50s. Heritability estimates for each drug were imprecise but altogether high (49-80%). Halothane and isoflurane EC50s were significantly correlated (r=0.71, P < 10(-9)). Genetic loci controlling sensitivity were found for both volatile anesthetics; the most significant determinant colocalized on chromosome V. A smaller recombinant inbred strain study of ethanol-induced immobility segregated different genetic effects that did not correlate with sensitivity to either halothane or isoflurane.

Conclusions
The genetic determinants driving the large variation in anesthetic sensitivity in these C. elegans recombinant inbred strains are very similar for halothane and isoflurane sensitivity.
Role of Spinal NO in Antiallodynic Effect of Intrathecal Clonidine in Neuropathic Rats
Authors: Pan Hui-Lin , Chen Shao-Rui , Eisenach James C. 
Published: November 2003

Background
The role of spinal nitric oxide (NO) in neuropathic pain remains uncertain. Although intrathecal clonidine causes NO release in the spinal cord, the functional role of spinal NO in clonidine-produced analgesia has not been examined. The objectives of this study were to assess the role of spinal NO in maintenance of allodynia and to determine the role of spinal NO in the antiallodynic effect of intrathecal clonidine.

Methods
Allodynia was produced in rats by tight ligation of the left L5-L6 spinal nerves. Intrathecal catheters were inserted with tips in the lumbar intrathecal space. Mechanical allodynia was determined by application of von Frey filaments to the left hindpaw. In the first series of experiments, allodynia was assessed before and after intrathecal injection of saline, L-arginine, an NO donor (SNAP), two NO synthase inhibitors (TRIM and NMMA), or an NO scavenger (PTIO). In the second series of experiments, 20 microg of clonidine was injected intrathecally 15 min after intrathecal injection of saline, TRIM, NMMA, or PTIO.

Results
Allodynia was not affected significantly by intrathecal injection of L-arginine, SNAP, TRIM, NMMA, or PTIO. The antiallodynic effect produced by intrathecal injection of clonidine was attenuated significantly by pretreatment with TRIM, NMMA, or PTIO.

Conclusions
These results demonstrate that spinal NO neither contributes significantly to maintenance of allodynia nor produces detectable antiallodynic effect in this neuropathic pain model. Furthermore, this study provides functional evidence that spinal NO plays an important role in the antiallodynic effect of intrathecal clonidine in neuropathic pain.
Differential Effects of Fentanyl and Morphine on Intracellular Ca2+Transients and Contraction in Rat Ventricular Myocytes
Authors: Kanaya Noriaki , Zakhary Daniel R. , Murray Paul A. , Damron Derek S. 
Published: November 2003

Background
Our objective was to elucidate the direct effects of fentanyl and morphine on cardiac excitation-contraction coupling using individual, field-stimulated rat ventricular myocytes.

Methods
Freshly isolated myocytes were loaded with fura-2 and field stimulated (0.3 Hz) at 28 degrees C. Amplitude and timing of intracellular Ca2+ concentration (at a 340:380 ratio) and myocyte shortening (video edge detection) were monitored simultaneously in individual cells. Real time Ca2+ uptake into isolated sarcoplasmic reticulum vesicles was measured using fura-2 free acid in the extravesicular compartment.

Results
The authors studied 120 cells from 30 rat hearts. Fentanyl (30-1,000 nM) caused dose-dependent decreases in peak intracellular Ca2+ concentration and shortening, whereas morphine (3-100 microM) decreased shortening without a concomitant decrease in the Ca2+ transient. Fentanyl prolonged the time to peak and to 50% recovery for shortening and the Ca2+ transient, whereas morphine only prolonged the timing parameters for shortening. Morphine (100 microM), but not fentanyl (1 microM), decreased the amount of Ca2+ released from intracellular stores in response to caffeine in intact cells, and it inhibited the rate of Ca2+ uptake in isolated sarcoplasmic reticulum vesicles. Fentanyl and morphine both caused a downward shift in the dose-response curve to extracellular Ca2+ for shortening, with no concomitant effect on the Ca2+ transient.

Conclusions
Fentanyl and morphine directly depress cardiac excitation-contraction coupling at the cellular level. Fentanyl depresses myocardial contractility by decreasing the availability of intracellular Ca2+ and myofilament Ca2+ sensitivity. In contrast, morphine depresses myocardial contractility primarily by decreasing myofilament Ca2+ sensitivity.
Assessment of Teratogenic Effects of Lidocaine in Rat Embryos Cultured In Vitro
Authors: Fujinaga Masahiko 
Published: November 2003

Background
Lidocaine has been reported to cause neural tube closure defects in vitro in mice at clinically relevant concentrations. However, no studies have been conducted to further investigate this potentially hazardous effect of lidocaine. This study was aimed to reassess teratogenic effects of lidocaine in vitro in rats.

Methods
Sprague-Dawley rat embryos were explanted at 8:00 AM on gestational day 9 and were cultured in medium containing various concentrations of lidocaine. (Embryos in the control group were cultured without lidocaine). After 50 h of culture, they were evaluated for growth size and morphology, including the neural tube closure.

Results
In the presence of 250 microM of lidocaine, embryos showed a increased incidence of situs inversus compared with control group but were otherwise normal. At 375 microM, embryos showed slight growth retardation but no significant morphologic abnormalities. At 500 microM, all viable embryos showed severe morphologic abnormalities. However, morphologic abnormalities were so-called nonspecific types and neural tube closure defects were not observed.

Conclusions
Results from the current study indicate that lidocaine causes teratogenic effects in vitro in rats only at concentrations much higher than clinically relevant concentrations. Furthermore, lidocaine did not cause neural tube closure defects at any concentrations evaluated.
Influence of Renal Failure on the Pharmacokinetics and Neuromuscular Effects of a Single Dose of Rapacuronium Bromide
Authors: Szenohradszky Janos , Caldwell James E. , Wright Peter M. C. , Brown Ronald , Lau Marie , Luks Andrew M. , Fisher Dennis M. 
Published: November 2003

Background
Because renal function affects the elimination of muscle relaxants, each new muscle relaxant must be evaluated in patients with renal failure. Accordingly, the neuromuscular effects and pharmacokinetics of rapacuronium were identified in patients with renal failure.

Methods
Rapacuronium (1.5 mg/kg) was administered to 10 healthy volunteers and 10 patients with renal failure who were undergoing non-transplant surgery, were 18-45 yr old, and were anesthetized with propofol. The adductor pollicis muscle twitch tension was monitored. Plasma samples were obtained frequently for a period of 8 h to measure the concentrations of ORG9487 and its metabolite, ORG9488. Pharmacokinetic parameters were determined using mixed-effects modeling.

Results
One patient was excluded from analysis because he was taking phenytoin chronically. Twitch depression at 1 min was less in patients than in healthy volunteers (median values: 92% in patients, 99% in volunteers). The times to 90% and peak twitch depression; to 10%, 25%, and 75% twitch recovery; and to 70% and 80% train-of-four ratios were similar in volunteers and patients. Rapacuronium's clearance was 32% less in patients with renal failure; in both groups, clearance decreased 0.909% per year of age compared with the value in a 30 yr old. The steady state distribution volume was 14% less in women than in men and 16% less in patients than in volunteers. For ORG9488, clearance was 85% less in patients than in volunteers.

Conclusions
The neuromuscular effects of a single dose of rapacuronium are affected minimally by renal failure. However, the decreased clearance of rapacuronium and its potent metabolite in renal failure suggests that repeated dosing of rapacuronium may lead to prolonged effects in patients with renal failure.
Morbidity and Mortality in Cirrhotic Patients Undergoing Anesthesia and Surgery
Authors: Ziser Avishai , Plevak David J. , Wiesner Russell H. , Rakela Jorge , Offord Kenneth P. , Brown David L. 
Published: November 2003

Background
Patients with cirrhosis have a reduced life expectancy. Anesthesia and surgery have been associated with clinical decompensation in patients with cirrhosis.

Methods
The authors retrospectively reviewed the records of all patients with the diagnosis of cirrhosis who underwent any surgical procedure under anesthesia at their institution between January 1980 and January 1991 (n = 733). Univariate and multivariate analyses were used to identify the variables associated with perioperative complications and short- and long-term survival.

Results
The perioperative mortality rate (within 30 days of surgery) was 11.6%. The perioperative complication rate was 30.1%. Postoperative pneumonia was the most frequent complication. Multivariate factors that were associated with perioperative complications and mortality included male gender, a high Child-Pugh score, the presence of ascites, a diagnosis of cirrhosis other than primary biliary cirrhosis (especially cryptogenic cirrhosis), an elevated creatinine concentration, the diagnosis of chronic obstructive pulmonary disease, preoperative infection, preoperative upper gastrointestinal bleeding, a high American Society of Anesthesiologists physical status rating, a high surgical severity score, surgery on the respiratory system, and the presence of intraoperative hypotension.

Conclusion
Risk factors have been identified for patients with cirrhosis who undergo anesthesia and surgery.
Sevoflurane Has No Effect on Sinoatrial Node Function or on Normal Atrioventricular and Accessory Pathway Conduction in Wolff-Parkinson-White Syndrome during Alfentanil/Midazolam Anesthesia
Authors: Sharpe Michael D. , Cuillerier Daniel J. , Lee John K. , Basta Magdi , Krahn Andrew D. , Klein George J. , Yee Raymond 
Published: November 2003

Background
The effects of sevoflurane on the electrophysiologic properties of the human heart are unknown. This study evaluated the effects of sevoflurane on the electrophysiologic properties of the normal atrioventricular conduction system, and on the accessory pathways in patients with Wolff-Parkinson-White syndrome, to determine its suitability as an anesthetic agent for patients undergoing ablative procedures.

Methods
Fifteen patients with Wolff-Parkinson-White syndrome undergoing elective radiofrequency catheter ablation were studied. Anesthesia was induced with alfentanil (20-50 microg/kg) and midazolam (0.15 mg/kg), and vecuronium (20 mg) and maintained with alfentanil (0.5 to 2 microg x kg(-1) x min(-1)) and midazolam (1 or 2 mg every 10-15 min, as required). An electrophysiologic study measured the effective refractory period of the right atrium, atrioventricular node, and accessory pathway; the shortest conducted cycle length of the atrioventricular node and accessory pathway during atrial pacing; the effective refractory period of the right ventricle and accessory pathway; and the shortest retrograde conducted cycle length of the accessory pathway during ventricular pacing. Parameters of sinoatrial node function included sinus node recovery time, corrected sinus node recovery time, and sinoatrial conduction time. Intraatrial conduction time and the atrial-His interval were also measured. Characteristics of induced reciprocating tachycardia, including cycle length, atrial-His, His-ventricular, and ventriculoatrial intervals, also were measured. Sevoflurane was administered to achieve an end-tidal concentration of 2% (1 minimum alveolar concentration), and the study measurements were repeated.

Results
Sevoflurane had no effect on the electrophysiologic parameters of conduction in the normal atrioventricular conduction system or accessory pathway, or during reciprocating tachycardia. However, sevoflurane caused a statistically significant reduction in the sinoatrial conduction time and atrial-His interval but these changes were not clinically important. All accessory pathways were successfully identified and ablated.

Conclusions
Sevoflurane had no effect on the electrophysiologic nature of the normal atrioventricular or accessory pathway and no clinically important effect on sinoatrial node activity. It is therefore a suitable anesthetic agent for patients undergoing ablative procedures.
Targeting Effect Compartment or Central Compartment Concentration of Propofol
Authors: Wakeling Howard G. , Zimmerman John B. , Howell Scott , Glass Peter S. A. 
Published: November 2003

Background
An effect compartment has been postulated, and the ke0 has been quantified for several intravenous anesthetic drugs using electroencephalography (EEG) as the measure of effect. The authors wanted to validate that loss of responsiveness (LOR) was related to targeting an effect compartment concentration rather than a central compartment (plasma) concentration.

Methods
Twenty American Society of Anesthesiologists physical status I and II patients were randomized to receive propofol administered to a target central compartment or target effect compartment site concentration of 5.4 microg/ml propofol administered by a target-controlled infusion (TCI) using a previously validated set of pharmacokinetic parameters and a ke0 of 0.63 min(-1). Every 30 s for the first 5 min and every minute for the second 5 min the patients were asked to open their eyes. The time to LOR was measured by a blinded investigator. The authors also simulated the time to reach the desired target effect site concentration using varying ke0 values.

Results
The median time to LOR in the group targeted to a predicted plasma propofol concentration was 3.02 min and 1.23 min in the group targeted to a predicted effect compartment propofol concentration (P < 0.05). LOR to command in both groups occurred at a predicted median effect compartment concentration of 4.55 microg/ml. Simulations demonstrated that the time predicted to LOR targeting an effect site concentration of 5.4 microg/ml is markedly altered by the value chosen for the ke0.

Conclusions
This study confirms the utility of the ke0 value to describe the effect compartment for propofol. The authors also illustrate the importance of selecting the correct ke0 value for the pharmacokinetic parameters used within the TCI system.
Equivalent Analgesia and Side Effects during Epidural and Pharmacokinetically Tailored Intravenous Infusion with Matching Plasma Alfentanil Concentration
Authors: Coda Barbara A. , Brown Mary Cleveland , Risler Linda BS , Syrjala Karen , Shen Danny D. 
Published: November 2003

Background
Recently, several clinical studies comparing intravenous and epidural infusions of fentanyl and its derivatives suggested that epidural infusions act primarily by systemic absorption to produce supraspinal analgesia. To evaluate this hypothesis, the authors used pharmacokinetically tailored intravenous infusions to produce matching plasma alfentanil concentrations during epidural and intravenous administration. The analgesia and side effects achieved with each mode of administration were compared.

Methods
Twelve volunteers participated in this placebo-controlled crossover study. The pain model was cutaneous electric stimulation of the finger and toe. The test battery included subjective rating of pain intensity; end-tidal carbon dioxide level; pupil size; ratings of alertness, nausea, and pruritus; and a plasma alfentanil assay. On one test day, the participants received epidural alfentanil (400 microg bolus + a 400-microg/h infusion for 2 h) and an intravenous saline infusion. The test battery was administered at regular intervals. On another test day, the participants received epidural saline and a computer-controlled intravenous infusion of alfentanil. The testing protocol was repeated as on the first test day. On the day the placebo was administered, the participants received epidural and intravenous saline infusions. The order of the placebo day was randomized.

Results
Plasma alfentanil concentration-time profiles were identical during epidural and intravenous infusions. A nearly equivalent analgesic response was observed with epidural and intravenous alfentanil at the upper and lower extremities. There were no differences in side effects for epidural and intravenous administration.

Conclusions
The systemic redistribution of alfentanil accounts for most of the analgesia and effects produced by epidural infusion.
Stereoselective Interaction of Ketamine with Recombinant [micro sign], [small kappa, Greek], and [small delta, Greek] Opioid Receptors Expressed in Chinese Hamster Ovary Cells
Authors: Hirota Kazuyoshi , Okawa Hirobumi , Appadu Balraj L. , Grandy David K. , Devi Lakshmi A. , Lambert David G. 
Published: November 2003

Background
The authors examined the interaction of ketamine with recombinant mu, kappa, and delta opioid receptors and recombinant orphan opioid receptors expressed in Chinese hamster ovary cells (CHO-mu, CHO-kappa, CHO-delta, and CHO(ORL1), respectively).

Methods
CHO-mu, CHO-kappa, and CHO-delta membranes were incubated with the opioid receptor radioligand [3H]diprenorphine at room temperature. Ketamine (racemic, R(-) and S(+)) was included at concentrations covering the clinical range. CHO(ORL1) membranes were incubated with [125I]Tyr(14)nociceptin and racemic ketamine at room temperature. The effects of racemic ketamine and selective opioid receptor agonists (mu: [D-Ala2, MePhe4, Gly(ol)5] enkephalin (DAMGO); kappa: spiradoline or delta: [D-pen2, D-pen5] enkephalin (DPDPE)) on forskolin-stimulated cyclic adenosine monophosphate formation also were examined. Data are mean +/- SEM.

Results
Racemic ketamine increased the radioligand equilibrium dissociation constant for [3H]diprenorphine from 85+/-5 to 273+/-11, 91+/-6 to 154+/-16, and 372+/-15 to 855+/-42 pM in CHO-mu, CHO-kappa, and CHO-delta, respectively. The concentration of radioligand bound at saturation was unaffected. In CHO-mu and CHO-kappa cells, racemic ketamine did not slow the rate of naloxone-induced [3H]diprenorphine dissociation. Ketamine and its isomers also displaced [3H]diprenorphine binding to mu, kappa, and delta receptors in a dose-dependent manner, with pKi values for racemic ketamine of 4.38+/-0.02, 4.55+/-0.04, and 3.57+/-0.02, respectively. S(+)-ketamine was two to three times more potent than R(-)-ketamine at mu and kappa receptors. Racemic ketamine displaced [125I]Tyr(14)nociceptin with an estimated affinity constant of 0.5 mM. Racemic ketamine inhibited the formation of cyclic adenosine monophosphate (naloxone insensitive) in a dose-dependent manner (concentration producing 50% inhibition approximately 2 mM) in all cell lines, including untransfected CHO cells. Ketamine (100 microM) reversed DAMGO (mu) and spiradoline (kappa) inhibition of formation of cyclic adenosine monophosphate.

Conclusions
Ketamine interacts stereoselectively with recombinant mu and kappa opioid receptors.