bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between Local Cerebral Blood Flow and Metabolism during Mild and Moderate Hypothermia in Rats
Authors: Frietsch Thomas , Krafft Peter , Piepgras Axel , Lenz Christian , Kuschinsky Wolfgang , Waschke Klaus F. 
Published: November 2003

Background
Hypothermia may interfere with the relationship between cerebral blood flow (CBF) and metabolism. Because this conclusion was based on the analysis of global values, the question remains whether hypothermic CBF/metabolism uncoupling exists on a local cerebral level. This study investigated the effects of hypothermic anesthesia on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU).

Methods
Thirty-six rats were anesthetized with isoflurane (1 minimum alveolar concentration) and artificially ventilated to maintain normal arterial carbon dioxide partial pressure (pH-stat). Pericranial temperature was maintained as normothermic (37.5 degrees C, n = 12) or was reduced to 35 degrees C (n = 12) or 32 degrees C (n = 12). Pericranial temperature was maintained constant for 60 min until LCBF or LCGU were measured by autoradiography. Twelve conscious rats served as normothermic controls.

Results
Compared with conscious animals, mean CBF remained unchanged during normothermic anesthesia. Mean CBF significantly increased during mild hypothermia but was unchanged during moderate hypothermia. During normothermic anesthesia, mean CGU was 45% lower than in conscious controls (P < 0.05). No further CGU reduction was found during mild hypothermia, whereas CGU further decreased during moderate hypothermia (48%; P < 0.05). Local analysis showed a linear LCBF/LCGU relationship in conscious (r = 0.94) and anesthetized (r = 0.94) normothermic animals, as well as in both hypothermic groups (35 degrees C: r = 0.92; 32 degrees C: r = 0.95; P < 0.05). The LCBF-to-LCGU ratio increased from 1.4 (conscious controls) to 2.4 (normothermic isoflurane) and 3.6 ml/micromol (mild and moderate hypothermia, P < 0.05).

Conclusions
Decrease of mean CGU at unchanged or increased mean CBF during hypothermic anesthesia may not indicate uncoupling. Local analysis shows a maintained linear relationship that is reset to a higher CBF/CGU ratio.
Isoflurane Increases the Apparent Agonist Affinity of the Nicotinic Acetylcholine Receptor by Reducing the Microscopic Agonist Dissociation Constant
Authors: Raines Douglas E. , Zachariah Vinu T. 
Published: November 2003

Background
Isoflurane increases the apparent agonist affinity of ligand-gated ion channels. This action reflects a reduction in the receptor's agonist dissociation constant and/or the preopen/open channel state equilibrium. To evaluate the effect of isoflurane on each of these kinetic constants in the nicotinic acetylcholine receptor, the authors analyzed isoflurane's actions on (1) the binding of the fluorescent agonist Dns-C6-Cho to the nicotinic acetylcholine receptor's agonist self-inhibition site and (2) the desensitization kinetics induced by the binding of the weak partial agonist suberyldicholine.

Methods
The dissociation constant for Dns-C6-Cho binding to the self-inhibitory site was determined using stopped-flow fluorescence spectroscopy. The values of the kinetic constants for agonist binding, channel gating, and desensitization were determined by modeling the suberyldicholine concentration-dependence of the apparent rate of desensitization.

Results
Isoflurane did not significantly alter the dissociation constant for Dns-C6-Cho binding to the self-inhibitory site even at a concentration as high as 1.5 mM, the highest concentration studied. At this concentration, isoflurane substantially reduced the dissociation constant for suberyldicholine binding to its channel opening site by 97% from 17 +/- 5 microM to 0.5 +/- 0.2 microM, whereas the preopen/open channel state equilibrium was reduced only from 19.1 to 5 +/- 1.

Conclusions
Isoflurane increases the apparent agonist affinity of the nicotinic acetylcholine receptor primarily by reducing the agonist dissociation constant of the site responsible for channel opening rather than altering channel gating kinetics.
Complete Prevention but Stimulus-dependent Reversion of Morphine Tolerance by the Glycine/NMDA Receptor Antagonist (+)-HA966 in Neuropathic Rats
Authors: Christensen Dennis , Guilbaud Gisèle , Kayser Valérie 
Published: November 2003

Background
Tolerance to the analgesic effect of morphine complicates the management of chronic pain states. The authors studied the ability of the glycine/N-methyl-D-aspartate receptor antagonist (+)-HA966 to modify morphine tolerance in a rat model of neuropathic pain.

Methods
Mononeuropathy was induced by placing four ligatures around the common sciatic nerve. The 4-day pretreatment regimens with two daily subcutaneous injections of saline and saline, saline and morphine (10 mg/kg), (+)-HA966 (2.5 mg/kg) and morphine, or (+)-HA966 and saline were begun on post-operative day 12 to test the ability of (+)-HA966 to prevent the development of tolerance. Behavioral experiments were performed on postoperative day 16, when the pain-related behavior reached a stable maximum. The effect of an acute dose of morphine (1 mg/kg intravenously) was tested against both mechanical (vocalization threshold to paw pressure) and thermal (struggle latency to hind paw immersion into a 46 degrees C hot-water bath) stimuli. In addition, to test the ability of a single injection of (+)-HA966 to reverse established morphine tolerance, groups of morphine-pretreated rats received injections of either (+)-HA966 (2.5 mg/kg subcutaneously) and morphine (1 mg/kg intravenously), saline and morphine, or (+)-HA966 and saline.

Results
Baseline vocalization thresholds and struggle latencies did not differ in the various pretreatment groups, indicating that the pretreatments had no effect on pain-related behavior. Coadministration of (+)-HA966 prevented the reduction of the effect observed with morphine alone in both the mechanical test and the thermal test. (+)-HA966 reversed morphine tolerance in the thermal but not in the mechanical test.

Conclusion
(+)-HA966 prevented morphine tolerance in both mechanical and thermal tests but reversed established morphine tolerance in the thermal test only.
Efficacy of Continuous Insufflation of Oxygen Combined with Active Cardiac Compression–Decompression during Out-of-hospital Cardiorespiratory Arrest
Authors: Saïssy Jean-Marie , Boussignac Georges , Cheptel Eric , Rouvin Bruno , Fontaine David , Bargues Laurent , Levecque Jean-Paul , Michel Alain , Brochard Laurent 
Published: November 2003

Background
During experimental cardiac arrest, continuous insufflation of air or oxygen (CIO) through microcannulas inserted into the inner wall of a modified intubation tube and generating a permanent positive intrathoracic pressure, combined with external cardiac massage, has previously been shown to be as effective as intermittent positive pressure ventilation (IPPV).

Methods
After basic cardiorespiratory resuscitation, the adult patients who experienced nontraumatic, out-of-hospital cardiac arrest with asystole, were randomized to two groups: an IPPV group tracheally intubated with a standard tube and ventilated with standard IPPV and a CIO group for whom a modified tube was inserted, and in which CIO at a flow rate of 15 l/min replaced IPPV (the tube was left open to atmosphere). Both groups underwent active cardiac compression-decompression with a device. Resuscitation was continued for a maximum of 30 min. Blood gas analysis was performed as soon as stable spontaneous cardiac activity was restored, and a second blood gas analysis was performed at admission to the hospital.

Results
The two groups of patients (47 in the IPPV and 48 in the CIO group) were comparable. The percentages of patients who underwent successful resuscitation (stable cardiac activity; 21.3 in the IPPV group and 27.1% in the CIO group) and the time necessary for successful resuscitation (11.8 +/- 1.8 and 12.8 +/- 1.9 min) were also comparable. The blood gas analysis performed after resuscitation (8 patients in the IPPV and 10 in the CIO group) did not show significant differences. The arterial blood gases performed after admission to the hospital and ventilation using a transport ventilator (seven patients in the IPPV group and six in the CIO group) showed that the partial pressure of arterial carbon dioxide (PaCO2) was significantly lower in the CIO group (35.7 +/- 2.1 compared with 72.7 +/- 7.4 mmHg), whereas the pH and the partial pressure of arterial oxygen (PaO2) were significantly higher (all P < 0.05).

Conclusions
Continuous insufflation of air or oxygen alone through a multichannel open tube was as effective as IPPV during out-of-hospital cardiac arrest. A significantly greater elimination of carbon dioxide and a better level of oxygenation in the group previously treated with CIO probably reflected better lung mechanics.
Malignant Hyperthermia Phenotype
Authors: Sigg Daniel C. , Iaizzo Paul A. 
Published: November 2003

Background
Succinylcholine causes immediate and severe arterial hypotension in swine with the malignant hyperthermia phenotype. The underlying mechanisms are unknown.

Methods
Malignant hyperthermia-susceptible (MHS; n = 10) and normal swine (n = 5) were anesthetized with thiopental. The following were monitored: electrocardiogram; arterial blood pressure; pulmonary artery, central venous, and left and right ventricular pressure; cardiac output; end-tidal carbon dioxide; core temperature; peripheral-blood flows; and arterial blood gases. After a control period, 2 mg/kg succinylcholine was given intravenously. Three MHS animals received 1 mg/kg vecuronium and two MHS animals received 2.5 mg/kg dantrolene intravenously. The effects of succinylcholine on left and right ventricular pressure and contractility were analyzed in isolated hearts. The effects of 0.06 mm succinylcholine on isometric tension development were recorded in isolated femoral artery rings.

Results
Succinylcholine caused an early, severe decrease in blood pressure, cardiac output, left ventricular pressure, and left ventricular contractility in MHS swine but not in normal swine; no significant differences were found in heart rate, right ventricular parameters, systemic vascular resistance, and preload (pulmonary diastolic pressure, central venous pressure). The succinylcholine-induced hypotension and associated effects were not prevented by dantrolene. However, pretreatment with high-dose vecuronium prevented not only the cardiovascular depression, but also MH. In addition, no phenotypic differences of succinylcholine on contractility or left ventricular pressure were observed in the isolated working hearts. Similary, succinylcholine did not cause a significantly different relaxation in rings in either phenotype.

Conclusion
Succinylcholine-induced hypotension occurred before muscle hypermetabolism in MHS swine. Succinylcholine had no differential physiologic effects on either the isolated heart or on isolated arteries. This hypotension could not be prevented by dantrolene but was prevented by pretreatment with high-dose vecuronium. Thus, an indirect mechanism such as the release of a cardiac depressant from skeletal muscle may have caused this hypotensive response.
Anesthesia-related Cardiac Arrest in Children
Authors: Morray Jeffrey P. , Geiduschek Jeremy M. , Ramamoorthy Chandra , Haberkern Charles M. , Hackel Alvin , Caplan Robert A. , Domino Karen B. , Posner Karen , Cheney Frederick W. 
Published: November 2003

Background
The Pediatric Perioperative Cardiac Arrest (POCA) Registry was formed in 1994 in an attempt to determine the clinical factors and outcomes associated with cardiac arrest in anesthetized children.

Methods
Institutions that provide anesthesia for children are voluntarily enrolled in the POCA Registry. A representative from each institution provides annual institutional demographic information and submits anonymously a standardized data form for each cardiac arrest (defined as the need for chest compressions or as death) in anesthetized children 18 yr of age or younger. Causes and factors associated with cardiac arrest are analyzed.

Results
In the first 4 yr of the POCA Registry, 63 institutions enrolled and submitted 289 cases of cardiac arrest. Of these, 150 arrests were judged to be related to anesthesia. Cardiac arrest related to anesthesia had an incidence of 1.4 +/- 0.45 (mean +/- SD) per 10,000 instances of anesthesia and a mortality rate of 26%. Medication-related (37%) and cardiovascular (32%) causes of cardiac arrest were most common, together accounting for 69% of all arrests. Cardiovascular depression from halothane, alone or in combination with other drugs, was responsible for two thirds of all medication-related arrests. Thirty-three percent of the patients were American Society of Anesthesiologists physical status 1-2; in this group, 64% of arrests were medication-related, compared with 23% in American Society of Anesthesiologists physical status 3-5 patients (P < 0.01). Infants younger than 1 yr of age accounted for 55% of all anesthesia-related arrests. Multivariate analysis demonstrated two predictors of mortality: American Society of Anesthesiologists physical status 3-5 (odds ratio, 12.99; 95% confidence interval, 2.9-57.7), and emergency status (odds ratio, 3. 88; 95% confidence interval, 1.6-9.6).

Conclusions
Anesthesia-related cardiac arrest occurred most often in patients younger than 1 yr of age and in patients with severe underlying disease. Patients in the latter group, as well as patients having emergency surgery, were most likely to have a fatal outcome. The identification of medication-related problems as the most frequent cause of anesthesia-related cardiac arrest has important implications for preventive strategies.
In Vivo Whole-Body Resting Energy Expenditure and Insulin Action in Human Malignant Hyperthermia
Authors: Freymond Daniel , Dériaz Olivier , Frascarolo Philippe , Reiz Sebastian , Jéquier Eric , Urwyler Albert 
Published: November 2003

Background
Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by volatile anesthetics or succinylcholine. The disorder is heterogenetic and caused by abnormal calcium regulation within skeletal muscle cells. No clear metabolic differences have been found in MH-susceptible (MHS) persons in vivo while not having MH episodes, but some reported signs suggest that insulin action and energy turnover might be altered in muscle of MHS persons.

Methods
In fasting and insulin-stimulated conditions, using the glucose clamp technique and indirect calorimetry, we assessed in vivo resting energy expenditure (REE) and nutrient utilization rates in 10 MHS, 5 MH-equivocal (MHE) and 10 MH-negative (MHN) persons from 14 families. With a model using the persons' fat-free mass, fat mass, age, and gender, we calculated their predicted REE and compared it with measured REE in 10 MHS and 10 MHN persons (measured - predicted = residual REE).

Results
In vivo measured REE and glucose disposal rates were similar in 10 MHS and 10 MHN persons. Only during insulin stimulation was residual REE greater in MHS persons (6.4%; P = 0. 013).

Conclusions
In vivo insulin action is unimpaired in MHS persons. Although the absolute values of whole-body REE are the same in MHS and MHN persons, the part of REE independent of the determinants fat-free mass, fat mass, age, and gender is moderately greater in MHS than in MHN persons during insulin exposure. This suggests that MH susceptibility might influence insulin-stimulated energy turnover in muscle.
Airway Occlusion Pressure to Titrate Positive End-expiratory Pressure in Patients with Dynamic Hyperinflation
Authors: Mancebo Jordi , Albaladejo Pierre , Touchard Dominique , Bak Ela , Subirana Mireia , Lemaire François , Harf Alain , Brochard Laurent 
Published: November 2003

Background
Although the use of external positive end-expiratory pressure (PEEP) is recommended for patients with intrinsic PEEP, no simple method exists for bedside titration. We hypothesized that the occlusion pressure, measured from airway pressure during the phase of ventilator triggering (P0.1t), could help to indicate the effects of PEEP on the work of breathing (WOB).

Methods
Twenty patients under assisted ventilation with chronic obstructive pulmonary disease were studied with 0, 5, and 10 cm H2O of PEEP while ventilated with a fixed level of pressure support.

Results
PEEP 5 significantly reduced intrinsic PEEP (mean +/- SD, 5.2 +/- 2.4 cm H2O at PEEP 0 to 3.6 +/- 1.9 at PEEP 5; P < 0.001), WOB per min (12. 6 +/- 6.7 J/min to 9.1 +/- 5.9 J/min; P = 0.003), WOB per liter (1.2 +/- 0.4 J/l to 0.8 +/- 0.4 J/l; P < 0.001), pressure time product of the diaphragm (216 +/- 86 cm H2O. s-1. min-1 to 155 +/- 179 cm H2O. s-1. min-1; P = 0.001) and P0.1t (3.3 +/- 1.5 cm H2O to 2.3 +/- 1.4 cm H2O; P = 0.002). At PEEP 10, no further significant reduction in muscle effort nor in P0.1t (2.5 +/- 2.1 cm H2O) occurred, and transpulmonary pressure indicated an increase in end-expiratory lung volume. Significant correlations were found between WOB per min and P0.1t at the three levels of PEEP (P < 0.001), and between the changes in P0.1t versus the changes in WOB per min (P < 0.005), indicating that P0.1t and WOB changed in the same direction. A decrease in P0.1 with PEEP indicated a decrease in intrinsic PEEP with a specificity of 71% and a sensitivity of 88% and a decrease in WOB with a specificity of 86% and a sensitivity of 91%.

Conclusion
These results show that P0.1t may help to assess the effects of PEEP in patients with intrinsic PEEP.
Difficult Intubation in Acromegalic Patients
Authors: Schmitt Hubert , Buchfelder Michael , Radespiel-Tröger Martin , Fahlbusch Rudolf 
Published: November 2003

Background
Previous studies have suggested that the incidence of difficult intubation in acromegalic patients is higher than in normal patients. However, these studies were retrospective and did not include preoperative assessment of the airways. The aims of this study were to determine the incidence of difficult intubation and to assess the usefulness of preoperative tests in predicting difficult laryngoscopy.

Methods
One hundred twenty-eight consenting acromegalic patients requiring general anesthesia and tracheal intubation were studied. Preoperatively, Mallampati classification, thyromental distance, and head and neck movement were determined in each patient. After induction of anesthesia and muscle paralysis, laryngoscopic grade was assessed during direct laryngoscopy; Cormack and Lehane grade III or IV were classified as difficult. The association of individual airway assessment with laryngeal view was evaluated using the Fisher exact test. Predictors of difficult laryngoscopy were evaluated by calculating their sensitivity and specificity.

Results
Laryngoscopy was difficult (grade III) in 33 of 128 patients (26%). Application of external laryngeal pressure improved laryngeal visualization to grade II in 20 of these 33 patients. In the remaining 13 patients (10%), intubation was difficult (more than two attempts, blade change, use of gum-elastic bougie). Mallampati classes 3 and 4 were significantly related to laryngoscopy grade III (Fisher exact test, P = 0.001).

Conclusions
The incidence of difficult laryngoscopy and intubation in acromegalic patients is higher than in normal patients. Preoperative Mallampati scores of 3 and 4 were of value in predicting difficult laryngoscopy. Nevertheless, even this test will miss a significant number of patients with a difficult airway.
Intestinal Inflammation and Morphine Tolerance Alter the Interaction between Morphine and Clonidine on Gastrointestinal Transit in Mice
Authors: Puig Margarita M. , Warner William , Pol Olga 
Published: November 2003

Background
Morphine and clonidine show synergy or antagonism inhibiting gastrointestinal transit depending on their proportion and level of effect. Their interaction during morphine tolerance and intestinal inflammation were assessed.

Methods
Gastrointestinal transit in mice was evaluated with charcoal and antitransit effects expressed as percent mean values +/- SEM. Tolerance was induced with a morphine pellet (75 mg) implanted for 72 h, and inflammation with intragastric croton oil. Dose-response curves for morphine and clonidine alone and combined at a 1:1 potency ratio were obtained, and doses producing a 50% and 60% inhibition were calculated (ED50, ED60). Interaction was established by isobolograms, interaction indexes, and analysis of variance.

Results
In naive and tolerant mice, the combination induced linear dose-response curves up to the ED60 and then reached a plateau. In naive mice, ED50 values were as follows: morphine 1.52 +/- 0.15 mg/kg, clonidine 0.09 +/- 0.008 mg/kg, and combined 0.506 +/- 0.084 mg/kg (0.478 +/- 0.08 mg/kg morphine plus 0.028 +/- 0.004 mg/kg clonidine). During tolerance, ED50 values were as follows: morphine 9.73 +/- 0.8 mg/kg, clonidine 0.09 +/- 0.007 mg/kg, combination 0.131 +/- 0.09 mg/kg (morphine 0. 13 +/- 0.09 mg/kg plus clonidine 0.0013 +/- 0.0005 mg/kg). In both groups, the interaction was synergistic up to the ED60 and antagonistic thereafter; synergy was enhanced during tolerance. During inflammation, ED50 values were as follows: morphine 0.17 +/- 0.04 mg/kg, clonidine 0.015 +/- 0.006 mg/kg, combined 0.62 +/- 0.04 mg/kg (morphine 0.568 +/- 0.04 mg/kg plus clonidine 0.052 +/- 0.004 mg/kg); thus, potencies of morphine and clonidine increased 9.3 and 7.1 times, while the combination remained unaltered. Moreover, inflammation transformed synergy into antagonism.

Conclusions
The interaction between morphine and clonidine was significantly altered during tolerance and inflammation. During tolerance, synergy was present up to 60% effect and then became antagonistic. Inflammation converted synergy to antagonism. A common pathway in signal transduction could partially explain the results.
Competence of the Internal Jugular Vein Valve Is Damaged by Cannulation and Catheterization of the Internal Jugular Vein
Authors: Wu Xianren , Studer Wolfgang , Erb Thomas , Skarvan Karl , Seeberger Manfred D. 
Published: November 2003

Background
Experimental results suggest that the competence of the internal jugular vein (IJV) valve may be damaged when the IJV is cannulated for insertion of a central venous catheter. It has further been hypothesized that the risk of causing incompetence of the proximally located valve might be reduced by using a more distal site for venous cannulation. The present study evaluated these hypotheses in surgical patients.

Methods
Ninety-one patients without preexisting incompetence of the IJV valve were randomly assigned to undergo distal or proximal IJV cannulation (> or = 1 cm above or below the cricoid level, respectively). Color Doppler ultrasound was used to study whether new valvular incompetence was present during Valsalva maneuvers after insertion of a central venous catheter, immediately after removal of the catheter, and, in a subset of patients, several months after catheter removal, when compared with baseline findings before cannulation of the IJV.

Results
Incompetence of the IJV valve was frequently induced both by proximal and distal cannulation and catheterization of the IJV. Its incidence was higher after proximal than after distal cannulation (76% vs. 41%; P < 0.01) and tended to be so after removal of the catheter (47% vs. 28%; P = 0.07). Valvular incompetence persisting immediately after removal of the catheter did not recover within 8-27 months in most cases.

Conclusions
Cannulation and catheterization of the IJV may cause persistent incompetence of the IJV valve. Choosing a more distal site for venous cannulation may slightly lower the risk of causing valvular incompetence but does not reliably avoid it.