bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose-dependent Enhancement of In Vivo GABAA–Benzodiazepine Receptor Binding by Isoflurane
Authors: Gyulai Ferenc E. , Mintun Mark A. , Firestone Leonard L. 
Published: November 2003

Background
Abundant in vitro and animal model data suggest the postsynaptic gamma-aminobutyric acid receptor type A (GABA(A)-R) is an important target for volatile general anesthetics, but the relevance of these models is untested in humans. Because benzodiazepines have also been shown to act via a specific GABA(A)-R site, they provide sensitive probes for the GABA(A)-R. Availability of the 11C-labeled benzodiazepine ligand, flumazenil, allowed us to quantitatively test in humans whether the volatile anesthetic isoflurane affects GABA(A)-Rs in vivo in a dose-dependent manner.

Methods
11C-flumazenil positron emission tomography scans were obtained in 12 healthy subjects while awake (control condition) and anesthetized with either 1.0 or 1.5 minimum alveolar concentration isoflurane (n = 7 and 5, respectively; isoflurane conditions). Regions of interest included areas of high, intermediate, and low GABA(A)-benzodiazepine site density. For each subject and experimental condition, the binding of 11C-flumazenil, expressed as distribution volume (which linearly correlates to maximal binding site density and apparent ligand affinity), was obtained by curve fitting using a two-compartment model.

Results
The ratio of distribution volume increased significantly in each examined region during the isoflurane conditions compared with control conditions (P < 0.01, one-tailed t test). Furthermore, the increases in ratio of distribution volume during the 1.5-minimum alveolar concentration isoflurane condition were significantly greater than those measured during 1.0 minimum alveolar concentration isoflurane inhalation (P < 0.002, one-tailed t test).

Conclusions
Isoflurane exposure appeared to enhance receptor-specific 11C-flumazenil binding in a dose-dependent manner. The results suggest the possibility that a conformational change of the GABA(A)-R is involved in the mechanism of action of isoflurane in the living human brain.
Different Patterns of Mast Cell Activation by Muscle Relaxants in Human Skin
Authors: Koppert Wolfgang , Blunk James A. , Petersen Lars J. , Skov Per , Rentsch Katharina , Schmelz Martin 
Published: November 2003

Background
Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the current study, dermal microdialysis was used for the investigation of mast cell activation by muscle relaxants. Dermal microdialysis enabled simultaneous assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic side effects.

Methods
Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each). After intradermal insertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a 60-min equilibration period, the muscle relaxants were delivered via the capillaries for 30 min, followed by a 30-min washout period. Dialysate was sampled at 15-min intervals, and histamine, mast cell tryptase, and protein extravasation were determined. Changes in skin blood flow were measured using a laser Doppler imager. Potency and efficacy were derived from nonlinear fittings of the dose-response curves.

Results
For succinylcholine and the isoquinolines, dose-response curves for the vascular and sensory effects paralleled the histamine and tryptase release. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase.

Conclusions
Dermal microdialysis has been successfully used to simultaneously assess mediator release, vascular reactions, and sensory effects. The different pattern of tryptase release by isoquinolines and aminosteroids suggests different mechanisms of mast cell activation.
Low-concentration Lidocaine Rapidly Inhibits Axonal Transport in Cultured Mouse Dorsal Root Ganglion Neurons
Authors: Kanai Akifumi , Hiruma Hiromi , Katakura Takashi , Sase Sumi , Kawakami Tadashi , Hoka Sumio 
Published: November 2003

Background
Axonal transport plays a critical role in supplying materials for a variety of neuronal functions such as morphogenetic plasticity, synaptic transmission, and cell survival. In the current study, the authors investigated the effects of the analgesic agent lidocaine on axonal transport in neurites of cultured mouse dorsal root ganglion neurons. In relation to their effects, the effects of lidocaine on the growth rate of the neurite were also examined.

Methods
Isolated mouse dorsal root ganglion cells were cultured for 48 h until full growth of neurites. Video-enhanced microscopy was used to observe particles transported within neurites and to measure the neurite growth during control conditions and in the presence of lidocaine.

Results
Application of 30 microM lidocaine immediately reduced the number of particles transported in anterograde and retrograde axonal directions. These effects were persistently observed during the application (26 min) and were reversed by lidocaine washout. The inhibitory effect was dose-dependent at concentrations from 0.1 to 1,000 microM (IC50 = 10 microM). In Ca2+-free extracellular medium, lidocaine failed to inhibit axonal transport. Calcium ionophore A23187 (0.1 microM) reduced axonal transport in both directions. The inhibitory effects of lidocaine and A23187 were abrogated by 10 microM KN-62, a Ca2+-calmodulin-dependent protein kinase II inhibitor. Application of such low-concentration lidocaine (30 microM) for 30 min reduced the growth rate of neurites, and this effect was also blocked by KN-62.

Conclusions
Low-concentration lidocaine rapidly inhibits axonal transport and neurite growth via activation of calmodulin-dependent protein kinase II.
Minimum Alveolar Concentration of Volatile Anesthetics in Rats during Postnatal Maturation
Authors: Orliaguet Gilles , Vivien Benoît , Langeron Olivier , Bouhemad Belaid , Coriat Pierre , Riou Bruno 
Published: November 2003

Background
Although neonatal rats have become widely used as experimental laboratory animals, minimum alveolar concentration (MAC) values of volatile anesthetics in rats during postnatal maturation remain unknown.

Methods
We determined MAC values of volatile anesthetics in spontaneously breathing neonatal (2-, 9-, and 30-day-old) and adult Wistar rats exposed to increasing (in 0.1-0.2% steps) concentrations of halothane, isoflurane, or sevoflurane (n = 12-20 in each group), using the tail-clamp technique. MAC and its 95% confidence intervals were calculated using logistic regression and corrected for body temperature (37 degrees C).

Results
In adult rats, inspired MAC values corrected at 37 degrees C were as follows: halothane, 0.88% (confidence interval, 0.82-0.93%); isoflurane, 1.12% (1.07-1.18%); and sevoflurane, 1.97% (1.84-2.10%). In 30-day-old rats, the values were as follows: halothane, 1.14% (1.07-1.20%); isoflurane, 1.67% (1.58-1.76%); and sevoflurane, 2.95% (2.75-3.15%). In 9-day-old rats, inspired MAC values were as follows: halothane, 1.68% (1.58-1.78%); isoflurane, 2.34% (2.21-2.47%); and sevoflurane, 3.74% (3.64-3.86%). In 2-day-old rats, inspired MAC values were as follows: halothane, 1.54% (1.44-1.64%); isoflurane, 1.86% (1.72-2.01%); and sevoflurane, 3.28% (3.09-3.47%).

Conclusion
As postnatal age increases, MAC value significantly increases, reaching the greatest value in 9-day-old rats, and decreases thereafter, and at 30 days is still greater than the adult MAC value.
Comparison of Two Different Temperature Maintenance Strategies during Open Abdominal Surgery
Authors: Janicki Piotr K. , Higgins Michael S. , Janssen Jill , Johnson Raymond F. , Beattie Charles 
Published: November 2003

Background
A new system has been developed that circulates warm water through a whole body garment worn by the patient during surgery. In this study the authors compared two different strategies for the maintenance of intraoperative normothermia. One strategy used a new water garment warming system that permitted active warming of both the upper and lower extremities and the back. The other strategy used a single (upper body) forced-air warming system.

Methods
In this prospective, randomized study, 53 adult patients were enrolled in one of two intraoperative temperature management groups during open abdominal surgery with general anesthesia. The water-garment group (n = 25) received warming with a body temperature (rectal) set point of 36.8 degrees C. The forced-air-warmer group (n = 28) received routine warming therapy using upper body forced-air warming system (set on high). The ambient temperature in the operating room was maintained constant at approximately 20 degrees C. Rectal, distal esophageal, tympanic, forearm, and fingertip temperatures were recorded perioperatively and during 2 h after surgery. Extubated patients in both groups were assessed postoperatively for shivering, use of additional warming devices, and subjective thermal comfort.

Results
The mean rectal and esophageal temperatures at incision, 1 h after incision, at skin closure, and immediately postoperatively were significantly higher (0.4-0.6 degrees C) in the group that received water-garment warming when compared with the group that received upper body forced-air warming. The calculated 95% confidence intervals for the above differences in core temperatures were 0.7-0.1, 0.8-0.2, 0.8-0.2, and 0.9-0.1, retrospectively. In addition, 14 and 7% of patients in the control upper body forced-air group remained hypothermic (< 35.5 degrees C) 1 and 2 h after surgery, respectively. No core temperature less than 35.5 degrees C was observed perioperatively in any of the patients from the water-garment group. A similar frequency of the thermal stress events (shivering, use of additional warming devices, subjective thermal discomfort) was observed after extubation in both groups during the 2 h after surgery.

Conclusions
The investigated water warming system, by virtue of its ability to deliver heat to a greater percentage of the body, results in better maintenance of intraoperative normothermia that does forced-air warming applied only to the upper extremities, as is common practice.
Respiratory Sites of Action of Propofol
Authors: Nieuwenhuijs Diederik , Sarton Elise , Teppema Luc J. , Kruyt Erik , Olievier Ida , van Kleef Jack , Dahan Albert 
Published: November 2003

Background
Propofol has a depressant effect on metabolic ventilatory control, causing depression of the ventilatory response to acute isocapnic hypoxia, a response mediated via the peripheral chemoreflex loop. In this study, the authors examined the effect of sedative concentrations of propofol on the dynamic ventilatory response to carbon dioxide to obtain information about the respiratory sites of action of propofol.

Methods
In 10 healthy volunteers, the end-tidal carbon dioxide concentration was varied according to a multifrequency binary sequence that involved 13 steps into and 13 steps out of hypercapnia (total duration, 1,408 s). In each subject, two control studies, two studies at a plasma target propofol concentration of 0.75 microg/ml (P(low)), and two studies at a target propofol concentration of 1.5 microg/ml (P(high)) were performed. The ventilatory responses were separated into a fast peripheral component and a slow central component, characterized by a time constant, carbon dioxide sensitivity, and apneic threshold. Values are mean +/- SD.

Results
Plasma propofol concentrations were approximately 0.5 microg/ml for P(low) and approximately 1.3 mg/ml for P(high), Propofol reduced the central carbon dioxide sensitivity from 1.5 +/- 0.4 to 1.2 +/- 0.3 (P(low); P < 0.01 vs. control) and 0.9 +/- 0.1 l x min(-1) x mmHg(-1) (P(high); P < 0.001 vs. control). The peripheral carbon dioxide sensitivity remained unaffected by propofol (control, 0.5 +/- 0.3; P(low), 0.5 +/- 0.2; P(high), 0.5 +/- 0.2 l x min(-1) x mmHg(-1)). The apneic threshold was reduced from 36.3 +/- 2.7 (control) to 35.0 +/- 2.1 (P(low); P < 0.01 vs. control) and to 34.6 +/- 1.9 mmHg (P(high); P < 0.01 vs. control).

Conclusions
Sedative concentrations of propofol have an important effect on the control of breathing, showing depression of the ventilatory response to hypercapnia. The depression is attributed to an exclusive effect within the central chemoreflex loop at the central chemoreceptors. In contrast to low-dose inhalational anesthetics, the peripheral chemoreflex loop, when stimulated with carbon dioxide, remains unaffected by propofol.
Effects of Mild Hypothermia on Blood–Brain Barrier Disruption during Isoflurane or Pentobarbital Anesthesia
Authors: Chi Oak Za , Liu Xia , Weiss Harvey R. 
Published: November 2003

Background
This study was performed to determine whether mild hypothermia (32 degrees C) could attenuate the degree of blood-brain barrier (BBB) disruption caused by a hyperosmolar solution and whether the degree of disruption would vary depending on anesthetic agents.

Methods
Rats were assigned to one of four groups: normothermic isoflurane, normothermic pentobarbital, hypothermic isoflurane, and hypothermic pentobarbital. During isoflurane (1.4%; normothermic or hypothermic) or pentobarbital (50 mg/kg administered intraperitoneally; normothermic or hypothermic) anesthesia, the external carotid artery and the femoral artery and vein were catheterized. Body temperature was maintained at 37 and 32 degrees C for the normothermic and hypothermic groups, respectively. To open the BBB, 25% mannitol was infused through the right carotid artery at the rate of 0.25 ml x kg(-1) x s(-1) for 30 s. The transfer coefficient of 14C-alpha-aminoisobutyric acid was determined.

Results
Blood pressure was similar among the four groups of animals. The degree of the BBB disruption by hyperosmolar mannitol was less with isoflurane than pentobarbital anesthesia in the normothermic groups (transfer coefficient: 29.9 +/- 17.1 and 50.4 +/- 17.5 microl x g(-1) x min(-1) for normothermic isoflurane and pentobarbital, respectively; P < 0.05). Mild hypothermia decreased the BBB disruption during anesthesia with both anesthetic agents (hypothermic isoflurane: 9.8 +/- 8.3 microl x g(-1) x min(-1), P < 0.05 vs. normothermic isoflurane; hypothermic pentobarbital: 30.2 +/- 13.9 microl x g(-1) x min(-1), P < 0.05 vs. normothermic pentobarbital), but the disruption was less during isoflurane anesthesia (hypothermic isoflurane vs. hypothermic pentobarbital, P < 0.005). In the contralateral cortex, there were no significant differences among these four experimental groups.

Conclusions
The data demonstrated that hypothermia was effective in attenuating BBB disruption by hyperosmolar mannitol during isoflurane as well as pentobarbital anesthesia. The degree of disruption appeared smaller during isoflurane than during pentobarbital anesthesia in both the normothermic as well as the hypothermic groups.
Antiallodynic Effect of Intrathecal Neostigmine Is Mediated by Spinal Nitric Oxide in a Rat Model of Diabetic Neuropathic Pain
Authors: Chen Shao-Rui , Khan Ghous M. , Pan Hui-Lin 
Published: November 2003

Background
Intrathecal administration of acetylcholinesterase inhibitors produces antinociception in both animals and humans, but their effect on diabetic neuropathic pain has not been studied. In the current study, we determined the antiallodynic effect of intrathecal injection of an acetylcholinesterase inhibitor, neostigmine, in a rat model of diabetic neuropathic pain. In addition, since acetylcholine can increase release of nitric oxide in the spinal cord, we studied the role of spinal endogenous nitric oxide in the action of intrathecal neostigmine in diabetic neuropathic pain.

Methods
Rats were rendered diabetic with an intraperitoneal 50-mg/kg injection of streptozotocin. Intrathecal catheters were inserted, with tips in the lumbar intrathecal space. Mechanical allodynia was determined by application of von Frey filaments to the hind paw. We first determined the dose-dependent effect of intrathecal neostigmine on allodynia. The role of spinal nitric oxide in the action of intrathecal neostigmine was then examined through intrathecal treatments with a neuronal nitric oxide synthase inhibitor (TRIM), a nitric oxide scavenger (PTIO), L-arginine, or D-arginine.

Results
The diabetic rats developed a sustained tactile allodynia within 4 weeks after streptozotocin injection. Intrathecal injection of 0.1-0.5 microg neostigmine dose-dependently increased the withdrawal threshold in response to application of von Frey filaments. Intrathecal pretreatment with 30 microg TRIM or 30 microg PTIO abolished the antiallodynic effect of intrathecal neostigmine. Furthermore, the inhibitory effect of TRIM on the action of intrathecal neostigmine was reversed by intrathecal injection of 100 microg L-arginine but not D-arginine.

Conclusions
Intrathecal neostigmine produces a profound analgesic effect in a rat model of diabetic neuropathic pain. Spinal endogenous nitric oxide contributes to the analgesic action of intrathecal neostigmine in this rat model of diabetic neuropathic pain.
Cardiac and Neurologic Complications Identify Risks for Mortality for Both Men and Women Undergoing Coronary Artery Bypass Graft Surgery
Authors: Hogue Charles W. , Sundt Thoralf , Barzilai Benico , Schecthman Kenneth B. , Dávila-Román Victor G. 
Published: November 2003

Background
Despite a number of studies showing that women and men respond to coronary artery bypass graft surgery differently, it is not known whether variables associated with mortality are the same for women and men. The purpose of this study was to identify variables independently associated with mortality for women undergoing coronary artery bypass graft surgery.

Methods
Single-institutional data were prospectively collected from 5,113 patients (1,558 or 30.5% women) undergoing coronary artery bypass graft surgery. The database was reviewed for patient characteristics and operative outcomes based on sex. Complications evaluated included low cardiac output syndrome (cardiac index < 2.0 l x min(-1) x m(-2) for > 8 h, regardless of treatment), stroke (new permanent global or focal motor deficits), Q-wave myocardial infarction, postoperative atrial fibrillation, and operative mortality.

Results
Women were older than men, and they were more likely to have preexisting hypertension, diabetes, and a history of stroke. Operative mortality for women was higher than for men (3.5% vs. 2.5%, P < 0.05). Compared with men, women were more likely to experience a postoperative myocardial infarction, stroke, and low cardiac output syndrome. When performing analysis on data from both sexes separately, low cardiac output syndrome, new stroke, myocardial infarction, and duration of cardiopulmonary bypass were independently associated with mortality for women and men both. Patient age was not independently associated with risk for mortality for women, but it was for men. However, when the authors combined both sexes in the logistic regression analysis, the age-sex interaction was not significant (P = 0.266), indicating that there was insufficient evidence to assert that age has a different effect on mortality for men and women.

Conclusions
These data confirm that women have higher perioperative mortality after coronary artery bypass graft surgery compared with men. A higher frequency of cardiac and neurologic complications seem to account to a large extent for the higher operative mortality for women. Factors independently associated with perioperative mortality are generally similar for women and men.
Intracuff Pressure and Tracheal Morbidity
Authors: Combes Xavier , Schauvliege Franck , Peyrouset Olivier , Motamed Cyrus , Kirov Kracen , Dhonneur Gilles , Duvaldestin Philippe 
Published: November 2003

Background
Diffusion of nitrous oxide into the cuff of the endotracheal tube results in an increase in cuff pressure. Excessive endotracheal tube cuff pressure may impair tracheal mucosal perfusion and cause tracheal damage and sore throat. Filling the cuff of the endotracheal tube with saline instead of air prevents the increase in cuff pressure due to nitrous oxide diffusion. This method was used to test whether tracheal morbidity is related to excess in tracheal cuff pressure during balanced anesthesia.

Methods
Fifty patients with American Society of Anesthesiologists physical status I or II were randomly allocated to two groups with endotracheal tube cuffs initially inflated to 20-30 cm H(2)O with either air (group A) or saline (group S). Anesthesia was maintained with isoflurane and nitrous oxide. At the time of extubation, a fiberoptic examination of the trachea was performed by an independent observer, and abnormalities of tracheal mucosa at the level of the cuff contact area were scored. Patients assessed their symptoms (sore throat, dysphagia, and hoarseness) at the time of discharge from the postanesthesia care unit and 24 h after extubation on a 101-point numerical rating scale.

Results
Cuff pressure increased gradually during anesthesia in group A but remained stable in group S. The incidence of sore throat was greater in group A than in group S in the postanesthesia care unit (76 vs. 20%) and 24 h after extubation (42 vs. 12%; P < 0.05). Tracheal lesions at time of extubation were seen in all patients of group A and in eight patients (32%) of group S (P < 0.05).

Conclusion
Excess in endotracheal tube cuff pressure during balanced anesthesia due to nitrous oxide diffusion into this closed gas space causes sore throat that is related to tracheal mucosal erosion.
Inhaled Furosemide Inhibits Behavioral Response to Airway Occlusion in Anesthetized Cats
Authors: Nehashi Shino , Nishino Takashi , Ide Tohru 
Published: November 2003

Background
A recent study showed that inhaled furosemide greatly improves experimentally induced dyspnea in humans. The objective of the current study is to test the hypothesis that inhaled furosemide suppresses the behavioral response to airway occlusion without changing the behavioral response to a somatic noxious stimulus in anesthetized animals.

Methods
In 10 spontaneously breathing cats anesthetized with isoflurane, anesthetic ED(50) was determined by measuring an end-tidal anesthetic concentration while observing escape behavior. The monitored behavior consisted of purposeful movement of the head and forearm after endotracheal tube occlusion. The duration from the start of airway occlusion to the onset of the positive response (DOCCL) was measured at the highest concentration of isoflurane permitting the positive motor response to airway occlusion before pretreatment. ED(50) values (minimum alveolar concentration) for the suppression of a somatic motor response to a noxious stimulus induced by toe pinch (toe-pinch ED(50)) were also determined. Then, the effects of inhaled furosemide or vehicle on the ED(50) for the suppression of the behavioral response to airway occlusion, DOCCL, and toe-pinch ED(50) were evaluated in a randomized, cross-over design.

Results
The ED(50) for the suppression of the behavioral response to airway occlusion significantly decreased (P < 0.01) and DOCCL was significantly prolonged (P < 0.01) after furosemide inhalation, whereas vehicle inhalation did not change these measurements. The decrease in ED(50) for the suppression of the behavioral response to airway occlusion after furosemide inhalation lasted 3 h. Furosemide inhalation did not affect the toe-pinch ED(50).

Conclusion
Inhaled furosemide suppressed the behavioral response to airway occlusion in anesthetized animals without affecting the response to somatic noxious stimulus. The authors' animal model of respiratory distress may be applicable to the study of dyspnea in regard to its mechanism and treatment.