bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analgesic Mechanisms of Ketamine in the Presence and Absence of Peripheral Inflammation
Authors: Kawamata Tomoyuki , Omote Keiichi , Sonoda Hajime , Kawamata Mikito , Namiki Akiyoshi 
Published: November 2003

Background
The studies on the mechanisms of ketamine antinociception have led to conflicting results. In this study, the authors investigated the contribution of supraspinal monoaminergic descending inhibitory system to ketamine analgesia for acute nociception and inflammation-induced hyperalgesia.

Methods
Male Sprague-Dawley rats were used. The paw withdrawal latencies to radiant heat stimuli were measured to assess the thermal nociceptive threshold. The analgesic effects of intrathecal or intraperitoneal ketamine were examined in the rats that received unilateral intraplantar carrageenan and in those that were untreated. In addition, it was examined whether pretreatment with intrathecal yohimbine or methysergide inhibited the analgesic effects of ketamine. Using an intrathecal microdialysis method, noradrenaline and 5-hydroxytryptamine concentrations in lumbar cerebrospinal fluid were measured after intraperitoneal ketamine in both saline- and carrageenan-treated rats.

Results
In the untreated rats, intraperitoneal but not intrathecal ketamine produced antinociceptive effects in a dose-dependent manner. Pretreatment with intrathecal yohimbine or methysergide inhibited these antinociceptive effects. Intraplantar carrageenan significantly reduced paw withdrawal latencies on the injected paw but not on the contralateral paw. Both intraperitoneal and intrathecal ketamine reversed the shortened paw withdrawal latencies on the injected side in a dose-dependent manner without any effects on the contralateral side. Neither yohimbine nor methysergide inhibited these antihyperalgesic effects. In analyses of monoamines, the magnitude of increase in monoamines after intraperitoneal ketamine was significantly smaller in the carrageenan-treated rats than in the saline-treated rats.

Conclusion
These results demonstrated that ketamine produced antinociceptive effects through an activation of the monoaminergic descending inhibitory system, whereas, in a unilateral peripheral inflammation-induced hyperalgesic state, the monoaminergic system did not contribute to the antihyperalgesic effects of ketamine. The mechanisms of the antinociceptive and antihyperalgesic properties of ketamine are different.
Core Cooling by Central Venous Infusion of Ice-cold (4°C and 20°C) Fluid
Authors: Rajek Angela , Greif Robert , Sessler Daniel I. , Baumgardner James , Laciny Sonja , Bastanmehr Hiva 
Published: November 2003

Background
Central venous infusion of cold fluid may be a useful method of inducing therapeutic hypothermia. The aim of this study was to quantify systemic heat balance and regional distribution of body heat during and after central infusion of cold fluid.

Methods
The authors studied nine volunteers, each on two separate days. Anesthesia was maintained with use of isoflurane, and on each day 40 ml/kg saline was infused centrally over 30 min. On one day, the fluid was 20 degrees C and on the other it was 4 degrees C. By use of a tympanic membrane probe core (trunk and head) temperature and heat content were evaluated. Peripheral compartment (arm and leg) temperature and heat content were estimated with use of fourth-order regressions and integration over volume from 18 intramuscular thermocouples, nine skin temperatures, and "deep" hand and foot temperature. Oxygen consumption and cutaneous heat flux estimated systemic heat balance.

Results
After 30-min infusion of 4 degrees C or 20 degrees C fluid, core temperature decreased 2.5 +/- 0.4 degrees C and 1.4 +/- 0.2 degrees C, respectively. This reduction in core temperature was 0.8 degrees C and 0.4 degrees C more than would be expected if the change in body heat content were distributed in proportion to body mass. Reduced core temperature resulted from three factors: (1) 10-20% because cutaneous heat loss exceeded metabolic heat production; (2) 50-55% from the systemic effects of the cold fluid per se; and (3) approximately 30% because the reduction in core heat content remained partially constrained to core tissues. The postinfusion period was associated with a rapid and spontaneous recovery of core temperature. This increase in core temperature was not associated with a peripheral-to-core redistribution of body heat because core temperature remained warmer than peripheral tissues even at the end of the infusion. Instead, it resulted from constraint of metabolic heat to the core thermal compartment.

Conclusions
Central venous infusion of cold fluid decreases core temperature more than would be expected were the reduction in body heat content proportionately distributed. It thus appears to be an effective method of rapidly inducing therapeutic hypothermia. When the infusion is complete, there is a spontaneous partial recovery in core temperature that facilitates rewarming to normothermia.
Physostigmine Reverses Propofol-induced Unconsciousness and Attenuation of the Auditory Steady State Response and Bispectral Index in Human Volunteers
Authors: Meuret Pascal , Backman Steven B. , Bonhomme Vincent , Plourde Gilles , Fiset Pierre 
Published: November 2003

Background
It is postulated that alteration of central cholinergic transmission plays an important role in the mechanism by which anesthetics produce unconsciousness. The authors investigated the effect of altering central cholinergic transmission, by physostigmine and scopolamine, on unconsciousness produced by propofol.

Methods
Propofol was administered to American Society of Anesthesiologists physical status 1 (n = 17) volunteers with use of a computer-controlled infusion pump at increasing concentrations until unconsciousness resulted (inability to respond to verbal commands, abolition of spontaneous movement). Central nervous system function was assessed by use of the Auditory Steady State Response (ASSR) and Bispectral Index (BIS) analysis of electrooculogram. During continuous administration of propofol, reversal of unconsciousness produced by physostigmine (28 microgram/kg) and block of this reversal by scopolamine (8.6 microgram/kg) were evaluated.

Results
Propofol produced unconsciousness at a plasma concentration of 3.2 +/- 0.8 (+/- SD) microgram/ml (n = 17). Unconsciousness was associated with reductions in ASSR (0.10 +/- 0.08 microV [awake baseline 0.32 +/- 0.18 microV], P < 0.001) and BIS (55.7 +/- 8.8 [awake baseline 92.4 +/- 3.9], P < 0.001). Physostigmine restored consciousness in 9 of 11 subjects, with concomitant increases in ASSR (0.38 +/- 0.17 microV, P < 0.01) and BIS (75.3 +/- 8.3, P < 0.001). In all subjects (n = 6) scopolamine blocked the physostigmine-induced reversal of unconsciousness and the increase of the ASSR and BIS (ASSR and BIS during propofol-induced unconsciousness: 0.09 +/- 0.09 microV and 58.2 +/- 7.5, respectively; ASSR and BIS after physostigmine administration: 0.08 +/- 0.06 microV and 56.8 +/- 6.7, respectively, NS).

Conclusions
These findings suggest that the unconsciousness produced by propofol is mediated at least in part via interruption of central cholinergic muscarinic transmission.
Diagnosing Sensory Abnormalities with Either Normal Values or Values from Contralateral Skin
Authors: Kemler Marius A. , Schouten Hubert J. A. , Gracely Richard H. 
Published: November 2003

Background
To diagnose sensory abnormalities, patient values can be compared with values of the general population (absolute approach) or to values measured at contralateral homologous skin (relative approach). The current study gives normal values for both approaches and compares the advantages of each method by applying the technique to patients with complex regional pain syndrome type I (CRPS I).

Methods
In 50 healthy control subjects, sensory and pain thresholds were measured for pressure, warmth, and cold on both wrists and both feet. In 53 patients with unilateral CRPS I (33 hand, 20 foot), the same assessments were conducted twice, at an interval of 1 month.

Results
In control subjects, contralateral homologous sides have approximately the same sensitivity, supporting the validity of the relative approach in patients. Hypoesthesia and allodynia can be diagnosed by either the absolute or relative approach, whereas hyperesthesia and hypoalgesia can only be identified with the relative approach. The two approaches obtain different results in 20% of cases. Age, gender, and subject criteria may influence the absolute but not the relative approach. Both approaches are comparable with regard to reproducibility. Frequency distributions of sensory abnormalities in chronic CRPS I are presented. The most frequent diagnoses were cold allodynia and mechanical hypoesthesia and allodynia.

Conclusions
To divide sensory characteristics into a binary classification of "normal" and "abnormal," the relative approach is the best choice, with the exception of cases in which the contralateral homologous side is absent or affected by disease. The authors recommend the relative approach for both research and clinical purposes.
Prevention of Isoflurane-induced Preconditioning by 5-Hydroxydecanoate and Gadolinium
Authors: Piriou Vincent , Chiari Pascal , Knezynski Sandra , Bastien Olivier , Loufoua Joseph , Lehot Jean-Jacques , Foëx Pierre , Annat Guy , Ovize Michel 
Published: November 2003

Background
Both mitochondrial adenosine triphosphate-sensitive potassium (MKATP) channels (selectively blocked by 5-hydroxydecanoate) and stretch-activated channels (blocked by gadolinium) have been involved in the mechanism of ischemic preconditioning. Isoflurane can reproduce the protection afforded by ischemic preconditioning. We sought to determine whether isoflurane-induced preconditioning may involve MKATP and stretch-activated channels.

Methods
Anesthetized open-chest rabbits underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Before this, rabbits were randomized into one of six groups and underwent a treatment period consisting of either no intervention for 40 min (control group; n = 9) or 15 min of isoflurane inhalation (1.1% end tidal) followed by a 15-min washout period (isoflurane group; n = 9). The two groups received an intravenous bolus dose of either 5-hydroxydecanoate (5 mg/kg) or gadolinium (40 micromol/kg) before coronary occlusion and reperfusion (5-hydroxydecanoate, n = 9; gadolinium, n = 7). Two additional groups received 5-hydroxydecanoate or gadolinium before isoflurane exposure (isoflurane-5-hydroxydecanoate, n = 10; isoflurane-gadolinium, n = 8). Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining.

Results
Area at risk was comparable among the six groups (29 +/- 7, 30 +/- 5, 27 +/- 6, 35 +/- 7, 31 +/- 7, and 27 +/- 4% of the left ventricle in the control, isoflurane, isoflurane-5-hydroxydecanoate, 5-hydroxydecanoate, isoflurane-gadolinium, and gadolinium groups, respectively). Infarct size averaged 60 +/- 20% (SD) in untreated controls versus 54 +/- 27 and 65 +/- 15% of the risk zone in 5-hydroxydecanoate- and gadolinium-treated controls (P = nonsignificant). In contrast, infarct size in the isoflurane group was significantly reduced to 26 +/- 11% of the risk zone (P < 0.05 vs.control). Both 5-hydroxydecanoate and gadolinium prevented this attenuation: infarct size averaged 68 +/- 23 and 56 +/- 21% of risk zone in the isoflurane-5-hydroxydecanoate and isoflurane-gadolinium groups, respectively (P = nonsignificant vs.control).

Conclusion
5-Hydroxydecanoate and gadolinium inhibited pharmacologic preconditioning by isoflurane. This result suggests that MKATP channels and mechanogated channels are probably involved in this protective mechanism.
Moxonidine, a Selective Imidazoline–α2-Adrenergic Receptor Agonist, Produces Spinal Synergistic Antihyperalgesia with Morphine in Nerve-injured Mice
Authors: Fairbanks Carolyn A. , Nguyen H. Oanh , Grocholski Brent M. , Wilcox George L. 
Published: November 2003

Background
Moxonidine, a novel imidazoline-alpha2-adrenergic receptor-selective analgesic, was recently identified as antinociceptive but has yet to be evaluated in neuropathic pain models. alpha2-adrenergic receptor-selective analgesics, and high-efficacy opioids, effectively inhibit neuropathic pain behaviors in rodents. In contrast, morphine potency and efficacy decreases in states of neuropathic pain, both in rodents and in humans, but may be restored or enhanced by coadministration of morphine with alpha2-adrenergic receptor-selective analgesics. The current experiments extend the evaluation of opioid-coadjuvant interactions in neuropathic subjects by testing the respective antihyperalgesic interactions of moxonidine and clonidine with morphine in a test of mechanical hyperalgesia.

Methods
Nerve-injured mice (Chung model) were spinally administered moxonidine, clonidine, morphine, and the combinations moxonidine-morphine and clonidine-morphine. Hyperalgesia was detected by von Frey monofilament stimulation (3.3 mN) to the hind paws (plantar surface). The ED50 values were calculated and the interactions tested by isobolographic analysis.

Results
In nerve-injured mice, moxonidine, clonidine, and morphine all dose-dependently inhibited mechanical hyperalgesia. Furthermore, the combinations of moxonidine-morphine and clonidine-morphine resulted in substantial leftward shifts in the dose-response curves compared with those of each agonist administered separately. The calculated ED50 values of the dose-response curves of these combinations were significantly lower than their corresponding theoretical additive ED50 values. These results confirmed that both interactions were synergistic.

Conclusions
Moxonidine and clonidine both synergize with morphine to inhibit paw withdrawal from nociceptive mechanical stimuli in nerve-injured mice.
Comparative Ventricular Electrophysiologic Effect of Racemic Bupivacaine, Levobupivacaine, and Ropivacaine on the Isolated Rabbit Heart
Authors: Mazoit Jean Xavier , Decaux Anne , Bouaziz Hervé , Edouard Alain 
Published: November 2003

Background
Numerous local anesthetics have an asymmetric tetrahedron carbon, which confers stereoselective differences between the isomers. The authors attempted to quantify the depressant effect of racemic bupivacaine, levobupivacaine, and ropivacaine on myocardial ventricular conduction and on myocardial contractility.

Methods
The authors studied the pharmacokinetics (outflow concentration) and pharmacodynamics (QRS widening) of the three drugs infused in an isolated rabbit heart preparation. All data were fitted simultaneously with use of mixed-effect modeling, thus allowing precise statistical comparison between the three drug parameters. The rate dependence of QRS widening was fitted separately.

Results
Racemic bupivacaine, levobupivacaine, and ropivacaine induced a calculated maximum increase in QRS duration in the ratio 1:0.4:0.3. Css50, the dose which caused half the maximum increase in QRS duration at steady state, was similar for all three drugs (22 micrometer free concentration). A rate dependence of QRS widening was observed, which was in the ratio 1:0.5:0.25 for racemic bupivacaine, levobupivacaine, and ropivacaine, respectively.

Conclusions
In the isolated rabbit heart, racemic bupivacaine, levobupivacaine, and ropivacaine induce an increase in QRS duration in the respective ratio of 1:0.4:0.3, which was rate dependent in approximately the same ratio.
Cardiac Troponin I and Myocardial Contusion in the Rabbit
Authors: Okubo Naomitsu , Hombrouck Cecile , Fornes Paul , Cosson Claudine , Samii Kamran , Mazoit Jean Xavier , Edouard Alain 
Published: November 2003

Background
Patients with cardiac contusion have a high risk of cardiac complications during emergency anesthesia. Despite the progress in cardiac imaging, a biologic marker of myocardial damage such as cardiac troponin I remains useful and has been proposed in clinical practice. The relationship among histologic injury, left-ventricular function, and release of cardiac enzymes and cardiac troponin I has been investigated after a controlled myocardial contusion in a rabbit model.

Methods
A global trauma (two levels of energy: 250 and 350 mJ) was produced on an isolated preparation of rabbit's heart, of which the temperature, perfusion flow, beating rate, and left-ventricular volume were kept constant. Left-ventricular pressure and its first derivative as a function of time were measured during a 60-min period after the blow; a timed collection of the effluent was made to assess creatine kinase, lactate dehydrogenase, and cardiac troponin I. At the end of the period, an anatomic score of the contusion was calculated by histologic examination of the hearts.

Results
Compared with a control group, the two levels of cardiac trauma resulted in a proportional anatomic injury significantly correlated with left-ventricular dysfunction (Delta%dP/dtmax = -16 +/- 12 and -36 +/- 20% at 3 min, mean +/- SD). Transient releases in cardiac markers after the lesser amount of trauma contrasted with a prolonged and biphasic release of cardiac troponin I after the greater amount. Peak cardiac troponin I level was correlated with anatomic injury (rho = 0.596, P= 0.001) and negatively correlated with left-ventricular dysfunction (r = -0.375, P= 0.04).

Conclusion
Cardiac troponin I is a marker of anatomic and functional consequences of experimental cardiac trauma and may be a predictive indicator of early posttraumatic cardiac complications during the postoperative period.
Desflurane Induces Only Minor Ca2+Release from the Sarcoplasmic Reticulum of Mammalian Skeletal Muscle
Authors: Kunst Gudrun , Stucke Astrid G. , Graf Bernhard M. , Martin Eike , Fink Rainer H. A. 
Published: November 2003

Background
Desflurane is a weaker trigger of malignant hyperthermia than is halothane. There are very few data of the pathophysiologic background of this observation. Therefore, the authors' aim was to investigate the direct effect of desflurane on calcium release in skinned skeletal muscle fibers.

Methods
For the measurements, single saponin-skinned muscle fiber preparations of BALB/c mice were used. For Ca2+ release experiments, liquid desflurane at 0.6 and 3.5 mm was applied to weakly calcium-buffered solutions with no added Ca2+. Desflurane was diluted in strongly Ca2+-buffered solutions, with [Ca2+] between 3.0 and 24.9 micrometer for [Ca2+]-force relations. Force transients were transformed into Ca2+ transients based on the individual [Ca2+]-force relations. As controls, 30 mm caffeine and equimolar sevoflurane were investigated in the same muscle fibers.

Results
At 3.5 mm, desflurane induced peak force transients of 8 +/- 4% (mean +/- SD) of maximal Ca2+-activated force (Tmax). These peak values were significantly smaller than those in the presence of 3.5 mm sevoflurane (24 +/- 10% of Tmax, P < 0.05), and 4 or 5 times smaller than previously reported Ca2+-release-induced force transients by equimolar halothane. Calculated peak Ca2+ transients derived from force transients and induced by 3.5 and 0.6 mm desflurane were significantly smaller than those induced by 30 mm caffeine. The [Ca2+]-force relation was shifted by desflurane, resulting in a Ca2+-sensitizing effect. The maximal Ca2+-activated force was significantly increased by 0.6 mm desflurane in comparison with the control, with no added substance (P </= 0.05).

Conclusion
Desflurane induces only slight Ca2+ release in skinned skeletal muscle fibers.
Emergence from Anesthesia in the Prone versus Supine Position in Patients Undergoing Lumbar Surgery
Authors: Olympio Michael A. , Youngblood B. Lee , James Robert L. 
Published: November 2003

Background
Conventional supine emergence in patients undergoing prone lumbar surgery frequently results in tachycardia, hypertension, coughing, and loss of monitoring as the patient is rolled supine. The prone position might facilitate a smoother emergence because the patient is not disturbed. No data describe this technique.

Methods
Fifty patients were anesthetized with fentanyl, nitrous oxide, isoflurane, and rocuronium. By the conclusion of surgery, all patients achieved spontaneous ventilation and full reversal of neuromuscular blockade in the prone position, as the volatile anesthetic level was reduced. Baseline heart rate and mean arterial pressure were recorded. Patients were then randomized at time 0 to the supine (n = 24) or prone (n = 21) position as 100% oxygen was administered. Patients in the supine position were then rolled over, while those in the prone position remained undisturbed. Heart rate, mean arterial pressure, and coughs were recorded until extubation. Tracheas were extubated on eye opening or purposeful behavior.

Results
When compared with the supine group, prone patients had significantly less increase in heart rate (P = 0.0003, maximum increase 9.3 vs. 25 beats/min), less increase in mean arterial pressure (P = 0.0063, maximum increase 4.8 vs. 19 mmHg), less coughing (P = 0.0004, 7.0 vs. 23 coughs), and fewer monitor disconnections (P < 0.0001). Time to extubation from time 0 was similar (4.0 vs. 3.7 min, prone vs. supine). No one required airway rescue. There was no significant difference in need for restraint (three prone, four supine).

Conclusions
Prone emergence and extubation is associated with less hemodynamic stimulation, less coughing, and less disruption of monitors, without specifically observed adverse effects, when compared with conventional supine techniques.
Transcranial Doppler Ultrasonography as a Screening Technique for Detection of a Patent Foramen Ovale before Surgery in the Sitting Position
Authors: Stendel Ruediger , Gramm Hans-Joachim , Schröder Klaus , Lober Conny , Brock Mario 
Published: November 2003

Background
Venous air embolism has been reported to occur in 23-45% of patients undergoing neurosurgical procedures in the sitting position. If venous air embolism occurs, a patent foramen ovale (PFO) is a risk factor for paradoxical air embolism and its sequelae. Preoperative screening for a PFO is therefore recommended by some investigators. The reference standard for identifying a PFO is contrast-enhanced transesophageal echocardiography (c-TEE). Contrast-enhanced transcranial Doppler ultrasonography (c-TCD) and contrast-enhanced transthoracic echocardiography (c-TTE) are noninvasive alternative methods, but so far there are no studies as to their diagnostic validity in neurosurgical patients.

Methods
The sensitivity and specificity of c-TCD and c-TTE in detecting a PFO were determined in a prospective study using c-TEE as the reference standard. Preoperative c-TCD, c-TTE, and c-TEE studies were performed during the Valsalva maneuver after intravenous echo-contrast medium (D-Galactose, Echovist-300, Schering AG, Berlin, Germany) was administered in 92 consecutive candidates (47 men and 45 women; mean age, 51 yr; range, 25-72 yr) before neurosurgical procedures in the sitting position.

Results
A PFO was detected in 24 of the 92 patients (26.0%) using c-TEE. c-TCD correctly identified 22 patients, whereas c-TTE only correctly identified 10. This corresponds to a sensitivity of 0.92 for c-TCD and 0.42 for c-TTE. The negative predictive value was 0.97 for c-TCD compared with 0.83 for c-TTE. The prevalence of a PFO in patients with a posterior fossa lesion was 27%, and in the group with cervical disc herniation was 24% as detected by c-TEE. The incidence of intraoperative venous air embolism was 35% in cases of cervical foraminotomy and 75% in posterior fossa surgery as detected by c-TEE.

Conclusions
c-TCD is a highly sensitive and highly specific method for detecting a PFO. Because c-TCD is noninvasive, it may be more suitable than c-TEE for routine preoperative screening for a PFO. C-TTE is not reliable in detecting a PFO.