bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolism of Glucose, Glycogen, and High-energy Phosphates during Transient Forebrain Ischemia in Diabetic Rats
Authors: Lanier William L. , Hofer Roger E. , Gallagher William J. 
Published: November 2003

Background
Hyperglycemia associated with diabetes mellitus will exacerbate neurologic injury after global brain ischemia. Studies in a rat model of forebrain ischemia (bilateral carotid occlusion plus hypotension for 10 min) discovered that acute restoration of normoglycemia in diabetics, using an insulin infusion, resulted in a neurologic outcome that was similar to normoglycemic rats without diabetes. The current study evaluated cerebral glucose, glycogen, lactate, and high-energy phosphate concentrations to identify metabolic correlates that might account for an alteration in postischemic outcome.

Methods
Fifty-four pentobarbital-anesthetized Sprague-Dawley rats were assigned to three groups: chronically hyperglycemic diabetic rats (D; N = 18); insulin-treated, acutely normoglycemic diabetic rats (ID; N = 18); and nondiabetic rats (ND; N = 18). These groups were further divided into groups of six rats each that received either no ischemia, forebrain ischemia of 10 min duration without reperfusion, or ischemia plus 15 min of reperfusion. Brains were excised after in situ freezing, and metabolites were measured using enzymatic fluorometric techniques.

Results
Before ischemia, D rats had greater concentrations of brain glucose (12.18 +/- 2.67 micromol/g) than did either ID (5.10 +/- 1.33) or ND (3.20 +/- 0.27) rats (P < 0.05). Preischemic brain glycogen was similar in all groups. At the completion of ischemia, brain lactate concentrations in D were 86% greater than in ID and 61% greater than in ND (P < 0.05), reflecting a higher intraischemic consumption of glucose plus glycogen in D (P < 0.05). High-energy phosphate concentrations, as assessed by the energy charge of the adenylate pool, were better preserved in D (energy charge = 0.60 +/- 0.28) than in either ID (0.29 +/- 0.09) or ND (0.36 +/- 0.07; P < 0.05) rats. After 15 min of reperfusion, the energy charge returned to preischemic values (i.e., 0.91-0.92) in all groups.

Conclusions
These studies demonstrated greater intraischemic carbohydrate consumption and lactate production in D than in ID or ND rats. Under these conditions, intraischemic-but not postischemic-energy status was better in D rats. Acute insulin therapy in ID rats resulted in a metabolic profile that was similar to that of ND rats. These results suggest that, in this model, primary energy failure during ischemia is not the origin of greater injury in hyperglycemic diabetics, nor is energy enhancement the origin of improved outcome after acute insulin treatment.
Pontine Cholinergic Mechanisms Modulate the Cortical Electroencephalographic Spindles of Halothane Anesthesia
Authors: Keifer J. C. , Baghdoyan H. A. , Lydic R. 
Published: November 2003

Background
Halothane anesthesia causes spindles in the electroencephalogram (EEG), but the cellular and molecular mechanisms generating these spindles remain incompletely understood. The current study tested the hypothesis that halothane-induced EEG spindles are regulated, in part, by pontine cholinergic mechanisms.

Methods
Adult male cats were implanted with EEG electrodes and trained to sleep in the laboratory. Approximately 1 month after surgery, animals were anesthetized with halothane and a microdialysis probe was stereotaxically placed in the medial pontine reticular formation (mPRF). Simultaneous measurements were made of mPRF acetylcholine release and number of cortical EEG spindles during halothane anesthesia and subsequent wakefulness. In additional experiments, carbachol (88 mM) ws microinjected in the the mPRF before halothane anesthesia to determine whether enhanced cholinergic neurotransmission in the MPRF would block the ability of halothane to induce cortical EEG spindles.

Results
During wakefulness, mPRF acetylcholine release averaged 0.43 pmol/10 min of dialysis. Halothane at 1 minimum alveolar concentration decreased acetylcholine release (0.25 pmol/10 min) while significantly increasing the number of cortical EEG spindles. Cortical EEG spindles caused by 1 minimum alveolar concentration halothane were not significantly different in waveform, amplitude, or number from the EEG spindles of nonrapid eye movement sleep. Microinjection of carbachol into the mPRF before halothane administration caused a significant reduction in number of halothane-induced EEG spindles.

Conclusions
Laterodorsal and pedunculopontine tegmental neurons, which provide cholinergic input to the mPRF, play a causal role in generating the EEG spindles of halothane anesthesia.
Desflurane-mediated Neurocirculatory Activation in Humans
Authors: Muzi Michael , Lopatka Craig W. , Ebert Thomas J. 
Published: November 2003

Background
Rapid increases in the inspired concentration of desflurane have been associated with sympathetic activation, tachycardia, hypertension, and in select cases, myocardial ischemia. The current study examined the effects of the rate of change of the desflurane concentration on the sympathetic and hemodynamic responses to desflurane and sought to determine whether a finite concentration (end-tidal) of desflurane consistently initiated these responses.

Methods
After Institutional Review Board approval, 23 healthy male volunteers were instrumented for electrocardiogram (heart rate (HR)), intraarterial blood pressure, and peroneal nerve microneurography (sympathetic nerve activity (SNA)). Subjects were given propofol (2.5 mg/kg) and vecuronium (0.15 mg/kg), and their lungs were mechanically ventilated for 30 min at a minimum alveolar concentration of 0.5 MAC with either desflurane or isoflurane (random assignment). The end-tidal concentration was increased at either 1% per min (n = 7) or 0.5% per min (n = 7) for desflurane or 0.16% per min (n = 9) for isoflurane (MAC-multiple comparable to 1% per min desflurane group) until 1.5 MAC was reached. HR, blood pressure, and SNA were averaged over 1-min segments from 0.5 to 1.5 MAC levels.

Results
Awake neurocirculatory variables did not differ among the three groups. At 0.5 MAC, blood pressure had decreased (12-15%) and HR increased (12-20%) similarly in both groups. SNA decreased 77% in the isoflurane group but was not significantly changed in the desflurane groups. In the desflurane groups, the threshold (end-tidal concentration associated with a 10% increase in the measured variable) ranged between 4% and 10% for HR and between 4% and 7.7% for SNA. In the isoflurane group, the threshold occurred between 1.0% and 1.6% for HR and between 0.7% and 1.3% for SNA. The rate of change did not affect the threshold concentration or the peak HR increase in the desflurane groups. In contrast, SNA responses to desflurane were directly proportional to the rate of change.

Conclusion
There was no consistent threshold for the neurocirculatory activation associated with desflurane, and the HR and SNA thresholds generally were less than 1 MAC. The HR increase associated with desflurane was not rate- or concentration-dependent. In contrast, SNA responses were proportional to the rate of change and the concentration of desflurane.
Derivation and Cross-validation of Pharmacokinetic Parameters for Computer-controlled Infusion of Lidocaine in Pain Therapy
Authors: Schnider Thomas W. , Gaeta Raymond , Brose William , Minto Charles F. , Gregg Keith M. , Shafer Steven L. 
Published: November 2003

Background
Lidocaine administered intravenously is efficacious in treating neuropathic pain at doses that do not cause sedation or other side effects. Using a computer-controlled infusion pump (CCIP), it is possible to maintain the plasma lidocaine concentration to allow drug equilibration between the plasma and the site of the drug effect. Pharmacokinetic parameters were derived for CCIP administration of lidocaine in patients with chronic pain.

Methods
Thirteen patients (mean age 45 yr, mean weight 66 kg) were studied. Eight subjects received a computer-controlled infusion, targeting four increasing lidocaine concentrations (1-7 micrograms.ml-1) for 30 min each, based on published kinetic parameters in which venous samples were obtained infrequently after bolus administration. From the observations in these eight patients, new lidocaine pharmacokinetic parameters were estimated. These were prospectively tested in five additional patients. From the complete data set (13 patients), final structural parameters were estimated using a pooled analysis approach. The interindividual variability was determined with a mixed-effects model, with the structural model parameters fixed at the values obtained from the pooled analysis. Internal cross-validation was used to estimate the residual error in the final pharmacokinetic model.

Results
The lidocaine administration based on the published parameters consistently produced higher concentrations than desired, resulting in acute lidocaine toxicity in most of the first eight patients. The highest measured plasma concentration was 15.3 micrograms.ml-1. The pharmacokinetic parameters estimated from these eight patients differed from the initial estimates and included a central volume one-sixth of the initial estimate. In the subsequent prospective test in five subjects, the new parameters resulted in concentrations evenly distributed around the target concentration. None of the second group of subjects had evidence of acute lidocaine toxicity. The final parameters ( +/- population variability expressed as %CV) were estimated as follows: V1 0.101 +/- 53% 1.kg-1, V2 0.452 +/- 33% 1.kg-1, Cl1 0.0215 +/- 25% 1.kg-1.min-1, and Cl2 0.0589 +/- 35% 1.kg-1.min-1. The median error measured by internal cross-validation was +1.9%, and the median absolute error was 14%.

Conclusions
Pharmacokinetic parameters for lidocaine were derived and administration was prospectively tested via computer-controlled infusion pumps for patients with chronic neuropathic pain. The estimated parameters performed well when tested prospectively. A second estimation step further refined the parameters and improved performance, as measured using internal cross-validation.
Parental Presence during Induction of Anesthesia
Authors: Kain Zeev N. , Mayes Linda C. , Caramico Lisa A. , Silver David , Spieker Martha , Nygren Margaret M. , Anderson George , Rimar Stephen 
Published: November 2003

Background
To determine whether parental presence during induction of anesthesia is an effective preoperative behavioral intervention, a randomized controlled trial with children undergoing outpatient surgery was conducted.

Methods
Eighty-four children were randomly assigned to a parent-present or parent-absent group. Using multiple behavioral and physiologic measures of anxiety, the effect of the intervention on the children and their parents was assessed. Predictors for the response to the intervention were examined using multivariate linear regression analysis.

Results
When the intervention group (parent-present) was compared to the control group (parent-absent), overall there were no significant differences in any of the behavioral or physiologic measures of anxiety tested during induction of anesthesia. Using the child's serum cortisol concentration as the outcome, parental presence, the child's age and baseline temperament, and trait anxiety of the parent, were identified as predictors of the child's anxiety during induction. Analysis of variance demonstrated that three groups showed diminished cortisol concentrations with parental presence: children older than 4 yr (P = 0.001), children whose parent had a low trait anxiety (P = 0.02), and children who had a low baseline level of activity as assessed by temperament (P = 0.05).

Conclusions
Children who were older than 4 yr or those with a parent with a low trait anxiety or who had a low baseline level of activity/temperament benefited from parental presence during induction.
Pharmacokinetics and Pharmacodynamics of Cisatracurium in Young and Elderly Adult Patients
Authors: Sorooshian Shahpoor S. , Stafford Michael A. , Eastwood Nigel B. , Boyd Alastair H. , Hull Christopher J. , Wright Peter M. C. 
Published: November 2003

Background
The effects of a muscle relaxant may differ in elderly compared with young adult patients for a variety of reasons. The authors compared the effects of a new muscle relaxant (cisatracurium) in young and elderly adults and used pharmacokinetic/pharmacodynamic modeling to identify factors explaining differences in time course of effect.

Methods
Thirty-one young (18-50 yr) and 33 elderly ( > 65 yr) patients anesthetized with nitrous oxide, isoflurane, and fetanyl were studied. Cisatracurium (0.1 mg/kg) was given after induction of anesthesia and later additional boluses of 0.025 mg/kg or an infusion of cisatracurium was given. Neuromuscular transmission was measured using the first twitch of the train-of-four response at the adductor pollicis after supramaximal stimulation of the ulnar nerve at 2 Hz every 15 s. Five venous blood samples were obtained for plasma drug concentration at intervals ranging from 2 to 120 min from every patient. Three additional samples were obtained from those who received an infusion. A population pharmacokinetic/pharmacodynamic model was fitted to the plasma concentration and effect data. The parameters of the model were permitted to vary with age to identify where differences existed between young and elderly adults.

Results
Onset of block was delayed in the elderly; values being mean 3.0 (95% confidence interval 1.75-11.4) min and 4.0 (2.4-6.5) min in the young and elderly, respectively (P < 0.01). Duration of action was similar in the two groups. Plasma clearance was 319 (293-345) ml/min in the study population and did not differ between young and elderly patients. Apparent volume of distribution was 13.28 (9.9-16.7) 1 and 9.6 (7.6-11.7) 1 in the elderly and young adults, respectively (P < 0.05). There also were differences in pharmacodynamic parameters between the young and elderly; the predominant change being a slower rate of biophase equilibration (ke0) in the elderly (0.060 [0.052-0.068])/min compared with the young (0.071 [0.065-0.077]/min; P < 0.05).

Conclusions
The pharmacokinetics of cisatracurium differ only marginally between young and elderly adults. Onset is delayed in the elderly because of slower biophase equilibration.
Repeated Doses of Rocuronium Bromide Administered to Cirrhotic and Control Patients Receiving Isoflurane
Authors: Servin Frederique S. , Lavaut Elisabeth , Kleef Ursula , Desmonts Jean Marie 
Published: November 2003

Background
Steroid muscle relaxants often display pharmacodynamic changes in patients with cirrhosis because of alterations in elimination processes. Rocuronium is a new steroid muscle relaxant possibly eliminated through the liver. This study was designed to compare rocuronium pharmacodynamics and pharmacokinetics in cirrhotic and healthy patients.

Methods
Rocuronium was administered to 26 cirrhotic patients and 24 control subjects anesthetized with isoflurane for an elective procedure. Patients were randomly allocated to received an initial dose of rocuronium: 120, 180, 250, or 300 micrograms.kg-1. Dose-response curves were established, and ED50 was calculated. Preselected maintenance doses (75, 150, or 225 micrograms.kg-1) were administered at 25% recovery of twitch height to compare clinical duration of action. At the end of the procedure, relaxation was reversed in half of the patients, and the time course of recovery was compared in the two groups. Blood samples drawn during the procedure and after the last maintenance dose allowed pharmacokinetic analysis in six cirrhotic patients and six control subjects.

Results
ED50 of the initial dose was 144 micrograms.kg-1 in cirrhotic patients and 60 micrograms.kg-1 in control subjects, related to a higher initial volume of distribution (cirrhotic 78.5 +/- 31.7 ml.kg-1, control 29.8 +/- 17.3 ml.kg-1). Time from complementary dose to 25% recovery was longer in cirrhotic patients (41.0 +/- 20.7 min vs 30.2 +/- 9.7 min), but time course of action during maintenance was not statistically different in the two groups. In cirrhotic patients receiving five maintenance doses or more, prolongation of the duration of action with successive maintenance doses could be statistically demonstrated. Spontaneous recovery was delayed in cirrhotic patients, because of impaired elimination processes: greater volume of distribution at steady-state (264 +/- 92 vs. 151 +/- 59 ml.kg-1); trend toward a lower clearance (189 +/- 60 vs. 296 +/- 169 ml.min-1).

Conclusions
Rocuronium pharmacodynamics are moderately altered by cirrhosis, possible because of pharmacokinetic alterations. Individual variability in response to rocuronium is great, and dosage should be carefully titrated to that required.
Fiberoptic Intubation Using Anesthetized, Paralyzed, Apneic Patients
Authors: Cole A. F. D. , Mallon J. S. , Rolbin S. H. , Ananthanarayan C. 
Published: November 2003

Background
There is no consensus about the best way to teach fiberoptic intubation. This study assesses the effectiveness of a training program in which novice anesthetic residents routinely were taught fiberoptic tracheal intubation of anesthetized, paralyzed, apneic patients.

Methods
Eight inexperienced anesthetic residents learned fiberoptic and conventional tracheal intubation simultaneously during their first 4 months of training. All intubations were performed using general anesthesia and muscle paralysis. Of these intubations, 223 (23%) were fiberoptic and 743 (77%) were laryngoscopic. Subsequently, their intubation skills with the two techniques were studied in a prospective, single-blind randomized trial involving 131 elective patients. Intubation times, SpO2, ETCO2, hemodynamic changes on intubation, and complications were recorded for 71 fiberoptic and 57 laryngoscopic intubations.

Results
There were two failures of the rigid and one failure of the fiberoptic technique due to inability to intubate within 180 s. In cases of failure, the tracheas were intubated successfully after mask ventilation by the alterative technique. No hypoxemia or hypercarbia occurred in any patient. There were no differences in hemodynamic indexes nor incidence of sore throat or hoarseness between the two groups. Mean intubation times were 56 +/- 24 s (mean +/- SD) for fiberoptic and 34 +/- 10 s (mean +/- SD) for laryngoscopic (P < 0.001).

Conclusions
Novices taught fiberoptic intubation and rigid laryngoscopic intubation under similar conditions, with similar volumes of experience, learn both techniques well. The safety and effectiveness of this training regimen commend it for inclusion in any residency program.
Rate of Coronary Flow Adaptation in Response to Changes in Heart Rate before and during Anesthesia for Coronary Artery Surgery
Authors: van Wezel Harry B. , Kal Jasper E. , Vergroesen Isabelle , Vroom Margreeth B. , De Graaf Ruud , Dankelman Jenny , Porsius Marjolein , Spaan Jos A. E. 
Published: November 2003

Background
The rate of adaptation of coronary blood flow in response to stepwise changes in heart rate (HR) has been extensively studied in dogs and goats to improve our understanding of the dynamics of coronary regulation processes and their pathophysiology and to obtain time constants for mathematical modeling of the coronary regulation. However, little is known about the dynamic characteristics of coronary flow adaptation in humans. In patients undergoing coronary artery surgery, we investigated the rate of coronary adaptation in response to stepwise changes in HR, in the awake and anesthetized states.

Methods
In 11 patients with stable coronary artery disease, arterial blood pressure, right atrial pressure, and coronary sinus blood flow, measured by continuous thermodilution, were calculated per beat. The ratio of beat-averaged arterial blood pressure minus right atrial pressure and coronary sinus blood flow was calculated to obtain an index of coronary resistance. The rate of change of coronary resistance index was quantified by t50, defined as the time required to establish 50% of the total change in coronary resistance index. Responses of coronary resistance index after HR changes, before and after induction of anesthesia, were compared. The anesthesia technique consisted of 100 micrograms.kg-1 fentanyl and 0.1 mg.kg-1 pancuronium bromide in combination with oxygen in air ventilation (FIO2 = 0.5).

Results
In the awake situation, t50 values of the dilating and constricting responses, induced by an increase and a decrease in HR were 5.0 +/- 2.1 (SD) s (range 2.6-9.0 s) and 5.7 +/- 1.2 s (range 4.1-7.8 s), respectively. During fentanyl/pancuronium anesthesia, the rate of coronary flow adaptation was significantly slower, with t50 values of 10.2 +/- 2.1 s (range 7.7-13.1 s) after an HR step-up and 9.8 +/- 2.1 s (range 6.6-13.2 s) after an HR step-down. Compared to the awake situation, arterial blood pressure was significantly reduced during anesthesia, but coronary vascular resistance remained unchanged. This implies that the steady-state static regulation of coronary blood flow had not changed.

Conclusions
These preliminary data suggest that, in patients with coronary artery disease, the rate of change in coronary vascular resistance in response to pacing-induced changes in HR is mitigated by fentanyl/pancuronium anesthesia during positive pressure ventilation. A further qualification of our findings in a larger number of patients is warranted.