bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphine Inhibits NF-κB Nuclear Binding in Human Neutrophils and Monocytes by a Nitric Oxide–dependent Mechanism
Authors: Welters Ingeborg D. , Menzebach Axel , Goumon Yannick , Cadet Patrick , Menges Thilo , Hughes Thomas K. , Hempelmann Gunter , Stefano George B. 
Published: November 2003

Background
The transcription factor NF-kappaB plays a pivotal role in gene expression of inflammatory mediators such as cytokines or adhesion molecules. NF-kappaB-mediated transcriptional activation of these genes is inhibited by nitric oxide (NO) in a variety of cells, including monocytes. Morphine mediates NO release in a naloxone antagonizable manner in monocytes and neutrophils.

Methods
The influence of morphine on NF-kappaB activation was investigated in a whole-blood flow cytometric assay. A specific antibody against the p65 subunit of NF-kappaB was used and detected by fluoresceine-isothiocyanate-labeled anti-immunoglobulin G. Nuclei were stained with propidium iodide. Leukocyte subpopulations were evaluated by gating on neutrophils and monocytes. The median fluorescence channel was determined. Different morphine concentrations (50 nm, 50 microm, 1 mm) and incubation intervals (10-150 min) were used.

Results
Morphine inhibits lipopolysaccharide-induced NF-kappaB nuclear binding in human blood neutrophils and monocytes in a time-, concentration-, and naloxone-sensitive-dependent manner. Similar effects were achieved with the NO donor S-nitroso-N-acetyl-pencillamine and the antioxidant N-acetyl-cysteine. The NO synthase inhibitors Nomega-nitro-l-arginine-methyl-esther and Nomega-nitro-l-arginine completely abolished the morphine-induced attenuation of NF-kappaB nuclear binding, demonstrating that the inhibitory action is mediated by NO release.

Conclusion
Morphine causes immunosuppression, at least in part, via the NO-stimulated depression of NF-kappaB nuclear binding.
Multiple Agents Potentiate α1-Adrenoceptor–induced Conduction Depression in Canine Cardiac Purkinje Fibers
Authors: Kulier Alexander H. , Turner Lawrence A. , Vodanovic Sanja , Contney Stephen , Lathrop David A. , Bosnjak Zeljko J 
Published: November 2003

Background
Halothane more so than isoflurane potentiates an alpha1-adrenoceptor (alpha1-AR)-mediated action of epinephrine that abnormally slows conduction in Purkinje fibers and may facilitate reentrant arrhythmias. This adverse drug interaction was further evaluated by examining conduction responses to epinephrine in combination with thiopental and propofol, which "sensitize" or reduce the dose of epinephrine required to induce arrhythmias in the heart, and with etomidate, which does not, and responses to epinephrine with verapamil, lidocaine, and l-palmitoyl carnitine, a potential ischemic metabolite.

Methods
Action potentials and conduction times were measured in vitro using two microelectrodes in groups of canine Purkinje fibers stimulated at 150 pulses/min. Conduction was evaluated each minute after exposure to 5 microm epinephrine (or phenylephrine) alone or with the test drugs. Changes in the rate of phase 0 depolarization (Vmax) and the electrotonic spread of intracellular current were measured during exposure to epinephrine with octanol to evaluate the role of inhibition of active and passive (intercellular coupling) membrane properties in the transient depression of conduction velocity.

Results
Lidocaine (20 microm) and octanol (0.2 mm) potentiated alpha1-AR-induced conduction depression like halothane (0.4 mm), with maximum depression at 3-5 min of agonist exposure, no decrease of Vmax, and little accentuation at a rapid (250 vs. 150 pulses/min) stimulation rate. Thiopental (95 microm), propofol (50 microm), and verapamil (2 microm) similarly potentiated epinephrine responses, whereas etomidate (10 microm) did not. Between groups, the decrease of velocity induced by epinephrine in the presence of (10 microm) l-palmitoyl carnitine (-18%) was significantly greater than that resulting from epinephrine alone (-6%; 0.05 </= P </= 0.10). Current injection experiments were consistent with marked transient inhibition of cell-to-cell coupling correlating with alpha1-AR conduction depression in fibers exposed to octanol.

Conclusions
Anesthetic "sensitization" to the arrhythmogenic effects of catecholamines may be a special case of a more general phenomenon by which not only some anesthetics and antiarrhythmic drugs but also possible ischemic fatty acid metabolites potentiate conduction depression due to acute alpha1-AR-mediated cell-to-cell uncoupling.
Volatile Anesthetics Activate the Human Tandem Pore Domain Baseline K+Channel KCNK5
Authors: Gray Andrew T. , Zhao Byron B. , Kindler Christoph H. , Winegar Bruce D. , Mazurek Matthew J. , Xu Jie , Chavez Raymond A. , Forsayeth John R. , Yost C. Spencer 
Published: November 2003

Background
Previous studies have identified a volatile anesthetic-induced increase in baseline potassium permeability and concomitant neuronal inhibition. The emerging family of tandem pore domain potassium channels seems to function as baseline potassium channels in vivo. Therefore, we studied the effects of clinically used volatile anesthetics on a recently described member of this family.

Methods
A cDNA clone containing the coding sequence of KCNK5 was isolated from a human brain library. Expression of KCNK5 in the central nervous system was determined by Northern blot analysis and reverse-transcription polymerase chain reaction. Functional expression of the channel was achieved by injection of cRNA into Xenopus laevis oocytes.

Results
Expression of KCNK5 was detected in cerebral cortex, medulla, and spinal cord. When heterologously expressed in Xenopus oocytes, KCNK5 currents exhibited delayed activation, outward rectification, proton sensitivity, and modulation by protein kinase C. Clinical concentrations of volatile general anesthetics potentiated KCNK5 currents by 8-30%.

Conclusion
Human KCNK5 is a tandem pore domain potassium channel exhibiting delayed activation and sensitivity to volatile anesthetics and may therefore have a role in suppressing cellular excitability during general anesthesia.
Sarcolemmal and Mitochondrial Adenosine Triphosphate– dependent Potassium Channels
Authors: Toller Wolfgang G. , Gross Eric R. , Kersten Judy R. , Pagel Paul S. , Gross Garrett J. , Warltier David C. 
Published: November 2003

Background
Volatile anesthetic-induced preconditioning is mediated by adenosine triphosphate-dependent potassium (KATP) channels; however, the subcellular location of these channels is unknown. The authors tested the hypothesis that desflurane reduces experimental myocardial infarct size by activation of specific sarcolemmal and mitochondrial KATP channels.

Methods
Barbiturate-anesthetized dogs (n = 88) were acutely instrumented for measurement of aortic and left ventricular pressures. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle (0.9% saline) or the nonselective KATP channel antagonist glyburide (0.1 mg/kg intravenously) in the presence or absence of 1 minimum alveolar concentration desflurane. In four additional groups, dogs received 45-min intracoronary infusions of the selective sarcolemmal (HMR 1098; 1 microg. kg-1. min-1) or mitochondrial (5-hydroxydecanoate [5-HD]; 150 microg. kg-1. min-1) KATP channel antagonists in the presence or absence of desflurane. Myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively.

Results
Desflurane significantly (P < 0.05) decreased infarct size to 10 +/- 2% (mean +/- SEM) of the area at risk as compared with control experiments (25 +/- 3% of area at risk). This beneficial effect of desflurane was abolished by glyburide (25 +/- 2% of area at risk). Glyburide (24 +/- 2%), HMR 1098 (21 +/- 4%), and 5-HD (24 +/- 2% of area at risk) alone had no effects on myocardial infarct size. HMR 1098 and 5-HD abolished the protective effects of desflurane (19 +/- 3% and 22 +/- 2% of area at risk, respectively).

Conclusion
Desflurane reduces myocardial infarct size in vivo, and the results further suggest that both sarcolemmal and mitochondrial KATP channels could be involved.
Single-beat Estimation of Ventricular End-systolic Elastance–Effective Arterial Elastance as an Index of Ventricular Mechanoenergetic Performance
Authors: Hayashi Kazuko , Shigemi Kenji , Shishido Toshiaki , Sugimachi Masaru , Sunagawa Kenji 
Published: November 2003

Background
The ratio of ventricular end-systolic elastance (Ees) to effective arterial elastance (Ea) is known to reflect not only ventricular mechanical performance but also energetic performance. Despite these useful features, technical difficulties associated with estimating Ees make the clinical application of Ees/Ea impractical. We developed a framework to estimate Ees/Ea without measuring ventricular volume or altering the loading condition.

Methods
To achieve this goal, we approximated the ventricular time-varying elastance curve with two straight lines, one for the isovolumic phase and the other for the ejection phase, and characterized the curve with the slope ratio, k, of these two straight lines. Using the concept of the pressure-volume relationship, Ees/Ea is algebraically expressed as Ees/Ea = Pad/Pes (1 + k. ET/PEP) - 1, where Pes is end-systolic pressure, Pad is aortic diastolic pressure, ET is ejection time, and PEP is pre-ejection period. In 11 anesthetized dogs, we recorded arterial and ventricular pressures and ventricular volume and estimated Ees and Ea under various contractile states and loading conditions.

Results
An empirical relation between k and Ees/Ea was found as k = 0.53 (Ees/Ea)0.51. Simultaneous solution of these two equations yielded Ees/Ea as a function of Pad/Pes and ET/PEP. The estimated Ees/Ea values correlated well with the measured Ees/Ea values ([Measured Ees/Ea] = 0.96 [Estimated Ees/Ea] + 0.098, r = 0.925, SEE = 0.051).

Conclusions
The proposed framework is capable of estimating Ees/Ea from ventricular and aortic pressure.
Hypersensitivity of Malignant Hyperthermia–susceptible Swine Skeletal Muscle to Caffeine Is Mediated by High Resting Myoplasmic [Ca2+]
Authors: López Jose R. , Contreras Jaime , Linares Nancy , Allen Paul D. 
Published: November 2003

Background
Malignant hyperthermia (MH) is an inherited pharmacogenetic syndrome that is triggered by halogenated anesthetics and/or depolarizing muscle relaxants. MH-susceptible (MHS) skeletal muscle has been shown to be more sensitive to caffeine-induced contracture than muscle from nonsusceptible (MHN) subjects and is the basis for the most commonly used clinical diagnostic test to determine MH susceptibility.

Methods
We studied the effects of caffeine on myoplasmic free calcium concentration ([Ca2+]i) in MHN and MHS swine muscle fibers by means of Ca2+-selective microelectrodes before and after K+-induced partial depolarization.

Results
[Ca2+]i in untreated MHN fibers was 123 +/- 8 nm versus 342 +/- 33 nm in MHS fibers. Caffeine (2 mm) caused an increase in [Ca2+]i in both groups (296 +/- 41 nm MHN vs. 1,159 +/- 235 nm MHS) with no change in resting membrane potential. When either MHN or MHS, muscle fibers were incubated in 10 mm K+ [Ca2+]i transiently increased to 272 +/- 22 nm in MHN and 967 +/- 38 nm in MHS for 6-8 min. Exposure of MHN fibers to 2 mm caffeine while resting [Ca2+]i was elevated induced an increment in [Ca2+]i to 940 +/- 37 nm. After 6-8 min of exposure to 10 mm K+, [Ca2+]i returned to control levels in all fibers, and the effect of 2 mm caffeine on resting [Ca2+]i returned to control, despite continued partial membrane depolarization.

Conclusions
These results suggest that the increased "sensitivity" to caffeine of MHS swine muscle fibers is a nonspecific response related, at least in part, to the high resting [Ca2+]i and not an increased caffeine sensitivity of the sarcoplasmic reticulum Ca2+ release channel per se.
Supplemental Intraoperative Oxygen Augments Antimicrobial and Proinflammatory Responses of Alveolar Macrophages
Authors: Kotani Naoki , Hashimoto Hiroshi , Sessler Daniel I. , Muraoka Masatoshi , Hashiba Eiji , Kubota Takeshi , Matsuki Akitomo 
Published: November 2003

Background
The first goal was to test the hypothesis that 100% inspired oxygen maintained for approximately 8 h intraoperatively is not associated with impaired pulmonary oxygenation. The authors also tested the hypothesis that intraoperative inhalation of 100% oxygen augments proinflammatory and antimicrobial responses of alveolar macrophages during anesthesia and surgery.

Methods
The authors studied patients administered 100% oxygen (n = 30) and 30% oxygen (n = 30) during propofol-fentanyl general anesthesia. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, 2, 4, and 6 h after induction of anesthesia, and at the end of surgery. The authors measured "opsonized" and "unopsonized" phagocytosis and microbicidal activity. RNA was extracted from harvested cells and cDNA was synthesized. The expression of interleukin(IL)-1beta, IL-6, IL-8, interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) was measured by semiquantitative polymerase chain reaction.

Results
Gene expression of all proinflammatory cytokines except IL-6 increased fourfold to 20-fold over time in both groups. However, expression of TNF-alpha and IL-8, IFN-gamma, and IL-6 and IL-1beta was 2-20 times greater in patients administered 100% than in those administered 30% oxygen. Unopsonized and opsonized phagocytosis and microbicidal activity decreased progressively, with the decreases being nearly twice as great during inhalation of 30% oxygen versus 100% oxygen.

Conclusion
Inhalation of 100% oxygen improved intraoperative decreases in phagocytic and microbicidal activity possibly because expression of proinflammatory cytokines was augmented. These data therefore suggest that intraoperative inhalation of 100% oxygen augments antimicrobial and proinflammatory responses in alveolar macrophages during anesthesia and surgery.
Comparison of Isoflurane Effects on Motor Evoked Potential and F Wave
Authors: Zhou Henry H. , Zhu Ching 
Published: November 2003

Background
Volatile anesthetics produce surgical immobility by suppressing the motor system. The anesthetic action site in the motor pathway is unclear. Anesthetic effects on the whole and the lower portion of motor pathway can be studied by measuring the motor evoked potentials (MEP) and the F wave. This study measured the effect of isoflurane on the MEP and the F wave.

Methods
With institutional review board approval, we studied 12 adult patients with American Society of Anesthesiologists physical status I or II. After intubation, anesthesia was maintained with nitrous oxide/oxygen and propofol infusion. MEPs were elicited by transcranial electrical stimuli (train-of-five pulse; stimuli intensity 40-160 mA) through electrodes placed in the scalp at C3/C4 positions and recorded at the anterior tibialis muscle with an Axon Sentinel-4EP monitor. F waves were elicited by an electrode fixed over the posterior tibial nerve at the medial malleolus and recorded at the abductor hallucis muscle. After end-tidal concentration of isoflurane was maintained at 0.5% for 20 min, the MEP and F wave were measured again. MEP and F-wave changes before and after isoflurane were analyzed using paired Wilcoxon test with Bonferroni correction. The difference between the changes in MEP and F wave was analyzed using Friedman's test.

Results
Motor evoked potential amplitudes (median, 205 microV; 25th-75th percentiles, 120-338 microV), F-wave amplitude (median, 100 microV; 25th-75th percentiles, 64.2-137.5 microV), and F-wave persistence (59 +/- 29%) were decreased to 0 microV (0-15 microV), 49 microV (12.4-99.6 microV), and 30 +/- 31%, respectively, by 0.5% isoflurane. MEP amplitude suppression was different from the changes in F-wave amplitude and persistence (P < 0.02).

Conclusions
Isoflurane 0.5% suppresses the motor pathway by decreasing both MEP and F wave. The MEP is suppressed more than the F wave.
Relation between Perioperative Hypertension and Intracranial Hemorrhage after Craniotomy
Authors: Basali Ayman , Mascha Edward J. , Kalfas Iain , Schubert Armin 
Published: November 2003

Background
Previous data suggest that systemic hypertension (HTN) is a risk factor for postcraniotomy intracranial hemorrhage (ICH). The authors examined the relation between perioperative blood pressure elevation and postoperative ICH using a retrospective case control design.

Methods
The hospital's database of all patients undergoing craniotomy from 1976 to 1992 was screened. Coagulopathic and unmatchable patients were excluded. There were 69 evaluable patients who developed ICH postoperatively (n = 69). A 2-to-1 matched (by age, date of surgery, pathologic diagnosis, surgical procedure, and surgeon) control group without postoperative ICH was assembled (n = 138). Preoperative, intraoperative, and postoperative blood pressure records (up to 12 h) were examined. Incidence of perioperative HTN (blood pressure > or = 160/90 mmHg) and odds ratios for ICH were determined.

Results
Of the 11,214 craniotomy patients, 86 (0.77%) suffered ICH, and 69 fulfilled inclusion criteria. The incidence of preoperative HTN was similar in the ICH (34%) and the control (24%) groups. ICH occurred 21 h (median) postoperatively, with an interquartile range of 4-52 h. Sixty-two percent of ICH patients had intraoperative HTN, compared with only 34% of controls (P < 0.001). Sixty-two percent of the ICH patients had prehemorrhage HTN in the initial 12 postoperative hours versus 25% of controls (P < 0.001), with an odds ratio of 4.6 (P < 0.001) for postoperative ICH. Hospital stay (median, 24.5 vs. 11.0 days), and mortality (18.2 vs. 1.6%) were significantly greater in the ICH than in the control groups.

Conclusions
ICH after craniotomy is associated with severely prolonged hospital stay and mortality. Acute blood pressure elevations occur frequently prior to postcraniotomy ICH. Patients who develop postcraniotomy ICH are more likely to be hypertensive in the intraoperative and early postoperative periods.
Regulation of Proprioceptive Memory by Subarachnoid Regional Anesthesia
Authors: Isaacson Sheldon A. , Funderburk Matthew , Yang Jay 
Published: November 2003

Background
Patient perception of limb position during regional anesthesia is frequently incorrect. The existing model ascribes this misperception, or phantom sensation, as a reversion to a fixed, slightly flexed, body schema. A model was developed to evaluate the influence of limb position changes on the incidence of incorrect or phantom sensations during regional anesthesia.

Methods
Forty American Society of Anesthesiologists physical status I-III adult patients undergoing genitourinary procedures under subarachnoid anesthesia were assigned to a lidocaine or bupivacaine treatment group and randomly assigned to one of four time groups (1, 4, 7, and 10 min). After blockade, patients were placed supine and blinded to limb positioning manipulations. One leg was flexed and the contralateral leg extended, with leg positions subsequently reversed at the assigned time point. At 10 min, patients were asked to identify the position of each leg. Percentage of incorrect response was analyzed using a logistic regression model with two independent variables: treatment and time. A supplemental study was undertaken to evaluate the observed difference in incorrect perceptions relative to flexed first versus extended limb first sequencing.

Results
The inability to perceive a change in limb position under regional anesthesia is dependent on the time after the block that the position change is initiated in relation to the onset characteristics of the local anesthetic. A phantom sensation of an extended leg position clearly exists. The flexed-first limb has a significantly higher incidence of incorrect or phantom perceptions.

Conclusion
Proprioceptive memory involves a dynamic neuroplastic imprinting process that is influenced by limb or joint position prior to onset of regional anesthesia. This contrasts with previously held beliefs of a purely fixed body schema.
Usefulness of Continuous Oxygen Insufflation into Trachea for Management of Upper Airway Obstruction during Anesthesia
Authors: Okazaki Junko , Isono Shiroh , Tanaka Atsuko , Tagaito Yugo , Schwartz Alan R. , Nishino Takashi 
Published: November 2003

Background
Severe complications associated with upper airway obstruction often occur during the perioperative period. Development of a simple and reliable technique for reversing the impaired airway patency may improve airway management. The purpose of the current study is to evaluate the usefulness of transtracheal oxygen insufflation (TTI) for management of upper airway obstruction during anesthesia and to explore the mechanisms of TTI in detail.

Methods
During propofol anesthesia in eight spontaneously breathing patients, the upper airway cross-sectional area and pressure-flow measurements during neck flexion with TTI were compared with those during triple airway maneuvers (TAM) without TTI. Blood gas analyses assessed efficacy of CO2 elimination during TTI in an additional nine patients.

Results
TTI achieved adequate PaCO2 and PaO2 levels equivalent to those during TAM. In addition to a significantly smaller cross-sectional area during TTI, the location and slope of the pressure-flow relation during TTI completely differed from those during TAM, indicating that upper airway resistance was much higher during TTI. Notably, minute ventilation during TTI was significantly smaller than that during TAM, suggesting reduced dead space or other mechanisms for CO2 elimination.

Conclusions
TTI is capable of maintaining adequate blood gases through mechanisms different from those of conventional airway support in anesthetized subjects with upper airway obstruction.