bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Pentobarbital and Isoflurane on Conditioned Learning after Transient Global Cerebral Ischemia in Rabbits
Authors: Kwon Jae Young , Bacher Andreas , Deyo Donald J. , Disterhoft John F. , Uchida Tatsuo , Zornow Mark H. 
Published: November 2003

Background
The acquisition of a conditioned eyeblink response has been used extensively to study the neurologic substrates of learning and memory. We examined the effects of the anesthetics isoflurane and pentobarbital, or hypothermia (30 degrees C), on the ability of rabbits to acquire an eyeblink conditioned response after 6.5 min of cerebral ischemia.

Methods
New Zealand white rabbits (n = 48) were randomly assigned to sham, normothermic, hypothermic, isoflurane, or pentobarbital groups. In the normothermic, hypothermic, isoflurane, and pentobarbital groups, 6.5 min of global cerebral ischemia was produced. In animals randomized to the isoflurane and pentobarbital groups, a pattern of burst suppression was achieved on the electroencephalogram before the start of the ischemic episode. Animals in the hypothermia group were cooled to 30 degrees C before ischemia. Seven days after ischemia, eyeblink training was started using an audible tone presented for 100 ms as the conditioned stimulus. The unconditioned stimulus was an air puff directed at the cornea. The delay between the end of conditioned stimulus and the start of the unconditioned stimulus (the trace interval) was 300 ms in duration. A conditioned response was defined as an eyeblink that was initiated during the trace interval. Eighty trials per day and 15 days of training were delivered.

Results
Neurologic deficits were greatest in the normothermia group, and these animals also had fewer conditioned responses than those in the sham, hypothermia, or pentobarbital groups. Animals in the isoflurane group had an intermediate number of conditioned responses that was not significantly different from the normothermia group.

Conclusions
This study demonstrates that a brief episode of cerebral ischemia results in the impairment of associative learning. Hypothermia and burst-suppressive doses of pentobarbital were able to improve neurobehavioral outcome as measured by ability to acquire a trace conditioned response.
Endotracheal Cardiac Output Monitor
Authors: Wallace Arthur W. , Salahieh Ali , Lawrence Andrew , Spector Ken , Owens Chris , Alonso David 
Published: November 2003

Background
The endotracheal cardiac output monitor (ECOM) is a new device that uses an endotracheal tube with multiple electrodes to measure cardiac output (CO). It measures the changes in electrical impedance caused by pulsatile blood flow in the aorta. The system was tested for safety and efficacy in 10 swine.

Methods
Swine (60-80 kg) were chronically instrumented with a transit time flow probe on the ascending aorta and vascular occluders on the vena cava and pulmonary artery. After a minimum recovery of 4 days, the animals were anesthetized and intubated with an ECOM endotracheal tube. CO measurements from the ECOM system were compared to transit time flow probe measurements using linear regression and Bland-Altman analysis. Three different inotropic states were studied: (1) baseline; (2) increased (dobutamine); and (3) decreased (esmolol). CO was changed at each inotropic state by impeding left ventricular filling with the vena cava or pulmonary artery occluders. CO values between 0 and 15 l/min were studied. Pigs were studied for 24 h consecutively.

Results
There was no deterioration of the impedance signal with time and no tracheal injury from the ECOM electrodes. There is a linear relationship between the ECOM and transit time flow probe CO between 0 and 15 l/min (slope = 0.94; intercept = 0.15 l/min; R2= 0.77). The mean difference between the two measures (bias) is 0.15 l/min and the SD is 1.34 l/min. The limits of agreement are -2.53 to 2.82 l/min.

Conclusion
Endotracheal CO monitor is a promising technology that needs further evaluation in clinical trials.
Lack of Whole-body Pharmacokinetic Differences of Halothane Enantiomers in the Rat
Authors: Mather Laurence E. , Fryirs Bronwyn L. , Duke Colin C. , Cousins Michael J. 
Published: November 2003

Background
Halothane is made and used as a racemate (an equimolar mixture of R- and S- enantiomers). This study was initiated to determine whether there were demonstrable enantiomeric differences in the whole-body pharmacokinetics of halothane that might have significance for studies in which racemate is used.

Methods
Adult male Wistar rats were exposed to halothane vaporized in the atmosphere of a closed constant volume chamber supplied with O2 commensurate with CO2 production. Concentrations of halothane enantiomers were measured by a specific gas chromatography-mass spectrometry method. Experiments were performed at four initial concentrations of halothane (0.1%, 0.5%, 1.0%, and 1.5% vol/vol). Enantiomeric differences in whole-body pharmacokinetics were assessed indirectly from the relative chamber atmosphere concentrations of halothane enantiomers.

Results
Concentrations of halothane decreased biphasically. The initial more rapid decrease was interpreted as incorporating absorption, distribution, and clearance; the slower decrease was interpreted as principally incorporating metabolic clearance. The ratio of concentrations of the two halothane enantiomers and of the ratios of the respective areas under the concentration-time curves remained constant without differing from unity at any time at any concentration of halothane. The dose-normalized areas under the concentration-time curves for the concentrations 0.1%, 0.5%, and 1.0% did not differ; that for 1.5% was significantly greater, suggesting nonlinear clearance, but the values did not differ significantly between enantiomers at any concentration.

Conclusions
As there were no significant differences in concentrations of the two enantiomers in the chamber atmosphere, enantioselectivity was not demonstrated in the whole-body pharmacokinetics of halothane.
Bupivacaine Inhibits Baroreflex Control of Heart Rate in Conscious Rats
Authors: Chang Kyoung S. K. , Morrow Don R. , Kuzume Kazuyo , Andresen Michael C. 
Published: November 2003

Background
Because exposure to intravenously administered bupivacaine may alter cardiovascular reflexes, the authors examined bupivacaine actions on baroreflex control of heart rate in conscious rats.

Methods
Baroreflex sensitivity (pulse interval vs. systolic blood pressure in ms/mmHg) was determined before, and 1.5 and 15.0 min after rapid intravenous administration of bupivacaine (0.5, 1.0, and 2.0 mg/kg) using heart rate changes evoked by intravenously administered phenylephrine or nitroprusside. The actions on the sympathetic and parasympathetic autonomic divisions of the baroreflex were tested in the presence of a muscarinic antagonist methyl atropine and a beta-adrenergic antagonist atenolol.

Results
Within seconds of injection of bupivacaine, mean arterial pressure increased and heart rate decreased in a dose-dependent manner. Baroreflex sensitivity was unaltered after administration of 0.5 mg/kg bupivacaine. In addition, 1 mg/kg bupivacaine at 1.5 min depressed phenylephrine-evoked reflex bradycardia (0.776 +/- 0.325 vs. 0.543 +/- 0.282 ms/mmHg, P < 0.05) but had no effect on nitroprusside-induced tachycardia. Bupivacaine (2 mg/kg), however, depressed reflex bradycardia and tachycardia (phenylephrine, 0.751 +/- 0.318 vs. 0.451 +/- 0.265; nitroprusside, 0.839 +/- 0.256 vs. 0.564 +/- 0.19 ms/mmHg, P < 0.05). Baroreflex sensitivity returned to prebupivacaine levels by 15 min. Bupivacaine (2 mg/kg), in the presence of atenolol, depressed baroreflex sensitivity (phenylephrine, 0.633 +/- 0.204 vs. 0.277 +/- 0.282; nitroprusside, 0.653 +/- 0.142 vs. 0.320 +/- 0.299 ms/mmHg, P < 0.05). In contrast, bupivacaine did not alter baroreflex sensitivity in the presence of methyl atropine.

Conclusions
Bupivacaine, in clinically relevant concentrations, inhibits baroreflex control of heart rate in conscious rats. This inhibition appears to involve primarily vagal components of the baroreflex-heart rate pathways.
Time-dependent Pressure Distortion in a Catheter–Transducer System
Authors: Promonet Claude , Anglade Daniel , Menaouar Ahmed , Bayat Sam , Durand Michel , Eberhard André , Grimbert Francis A. 
Published: November 2003

Background
Distortion of the pressure wave by a liquid-filled catheter-transducer system leads most often to an overestimation in systolic arterial blood pressure in pulmonary and systemic circulations. The pressure distortion depends on the catheter-transducer frequency response. Many monitoring systems use either mechanical or electronic filters to reduce this distortion. Such filters assume, however, that the catheter-transducer frequency response does not change over time. The current study aimed to study the changes with time of the catheter-transducer frequency response and design a flush procedure to reverse these changes back to baseline.

Methods
An in vitro setup was devised to assess the catheter-transducer frequency response in conditions approximating some of those met in a clinical environment (slow flushing, 37 degrees C, 48-h test). Several flush protocols were assessed.

Results
Within 48 h, catheter-transducer natural frequency decreased from 17.89 +/- 0.36 (mean +/- SD) to 7.35 +/- 0.25 Hz, and the catheter-transducer damping coefficient increased from 0.234 +/- 0.004 to 0.356 +/- 0.010. Slow and rapid flushing by the flush device built into the pressure transducer did not correct these changes, which were reversed only by manual fast flush of the transducer and of the catheter. These changes and parallel changes in catheter-transducer compliance may be explained by bubbles inside the catheter-transducer.

Conclusions
Catheter-transducer-induced blood pressure distortion changes with time. This change may be reversed by a manual fast flush or "rocket flush" procedure, allowing a con. stant correction by a filter.
Lumbar Epidural Morphine in Humans and Supraspinal Analgesia to Experimental Heat Pain
Authors: Angst Martin S. , Ramaswamy Bhamini , Riley Ed T. , Stanski Donald R. 
Published: November 2003

Background
Epidural administration of morphine is a common analgesic technique to manage pain. Morphine spreads from the epidural space to the cerebrospinal fluid and then rostrally, causing side effects mediated by the brain stem. However, data on the rostral spread of morphine-mediated analgesia are sparse. This study examined the rostral spread of analgesic effects on heat and electrical pain after epidural administration of morphine.

Methods
In a randomized, double-blinded, placebo-controlled, crossover study, 5 mg morphine or saline placebo were injected into the lumbar epidural space in nine healthy volunteers. Correct needle placement was confirmed with fluoroscopy. Analgesia to experimental nociceptive heat and electrical stimuli was measured at lumbar (L4), thoracic (T10), cervical (C2), and trigeminal (V2) levels before and 2, 5, 10, and 24 h after epidural injection. Plasma samples for assaying morphine concentrations were drawn before and after each analgesic evaluation.

Results
Epidural morphine significantly attenuated experimental heat pain at all dermatomes tested compared with saline placebo. Analgesic effects were significant at L4 after 2, 5, and 10 h, at T10 after 5, 10, and 24 h, and at V2 after 10 h. Electrical pain was attenuated at the lumbar and thoracic but not at the cervical dermatome. Analgesic effects were significant at L4 after 2, 5, and 10 h and at T10 after 5 and 10 h. Morphine plasma concentrations were below the detection limit (1 ng/ml) in eight of the nine subjects 10 h after epidural injection.

Conclusions
Lumbar epidural injection of morphine attenuated cutaneous heat pain up to the trigeminal dermatome during a 24-h observation period. In a clinical context, this implies that some types of pain may be attenuated up to the supraspinal level after lumbar epidural administration of morphine.
A Direct Search Procedure to Optimize Combinations of Epidural Bupivacaine, Fentanyl, and Clonidine for Postoperative Analgesia
Authors: Curatolo Michele , Schnider Thomas W. , Petersen-Felix Steen , Weiss Susanne , Signer Christoph , Scaramozzino Pasquale , Zbinden Alex M. 
Published: November 2003

Background
The authors applied an optimization model (direct search) to find the optimal combination of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate for continuous postoperative epidural analgesia.

Methods
One hundred ninety patients undergoing 48-h thoracic epidural analgesia after major abdominal surgery were studied. Combinations of the variables of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate were investigated to optimize the analgesic effect (monitored by verbal descriptor pain score) under restrictions dictated by the incidence and severity of side effects. Six combinations were empirically chosen and investigated. Then a stepwise optimization model was applied to determine subsequent combinations until no decrease in the pain score after three consecutive steps was obtained.

Results
Twenty combinations were analyzed. The optimization procedure led to a reduction in the incidence of side effects and in the mean pain scores. The three best combinations of bupivacaine dose (mg/h), fentanyl dose (microg/h), clonidine dose (microg/h), and infusion rate (ml/h) were: 9-21-5-7, 8-30-0-9, and 13-25-0-9, respectively.

Conclusions
Given the variables investigated, the aforementioned combinations may be the optimal ones to provide postoperative analgesia after major abdominal surgery. Using the direct search method, the enormous number of possible combinations of a therapeutic strategy can be reduced to a small number of potentially useful ones. This is accomplished using a scientific rather than an arbitrary procedure.
Pharmacokinetics of Dopamine in Healthy Male Subjects
Authors: MacGregor Drew A. , Smith Timothy E. , Prielipp Richard C. , Butterworth John F. , James Robert L. , Scuderi Phillip E. 
Published: November 2003

Background
Dopamine is an agonist of alpha, beta, and dopaminergic receptors with varying hemodynamic effects depending on the dose of drug being administered. The purpose of this study was to measure plasma concentrations of dopamine in a homogeneous group of healthy male subjects to develop a pharmacokinetic model for the drug. Our hypothesis was that dopamine concentrations can be predicted from the infusion dose using a population-based pharmacokinetic model.

Methods
Nine healthy male volunteers aged 23 to 45 yr were studied in a clinical research facility within our academic medical center. After placement of venous and arterial catheters, dopamine was infused at 10 microg x kg(-1) x min(-1) for 10 min, followed by a 30-min washout period. Subsequently, dopamine was infused at 3 microg x kg(-1) x min(-1) for 90 min, followed by another 30-min washout period. Timed arterial blood samples were centrifuged, and the plasma was analyzed by high-performance liquid chromatography. Mixed-effects pharmacokinetic models using NONMEM software (NONMEM Project Group, University of California, San Francisco, CA) were used to determine the optimal compartmental pharmacokinetic model for dopamine.

Results
Plasma concentrations of dopamine varied from 12,300 to 201,500 ng/l after 10 min of dopamine infusion at 10 microg x kg(-1) x min(-1). Similarly, steady-state dopamine concentrations varied from 1,880 to 18,300 ng/l in these same subjects receiving 3-microg x kg(-1) x min(-1) infusions for 90 min. A two-compartment model adjusted for body weight was the best model based on the Schwartz-Bayesian criterion.

Conclusions
Despite a homogeneous population of healthy male subjects and weight-based dosing, there was 10- to 75-fold intersubject variability in plasma dopamine concentrations, making standard pharmacokinetic modeling of less utility than for other drugs. The data suggest marked intraindividual and interindividual variability in dopamine distribution and/or metabolism. Thus, plasma dopamine concentrations in patients receiving dopamine infusion at identical rates may vary profoundly. Our data suggest that dosing dopamine based on body weight does not yield predictable blood concentrations.
Efficacy of Neurolytic Celiac Plexus Block in Varying Locations of Pancreatic Cancer
Authors: Rykowski Jan J. , Hilgier Maciej 
Published: November 2003

Background
Neurolytic celiac plexus block (NCPB) is an effective way of treating severe pain in some patients with pancreatic malignancy. However, there are no studies to date that evaluate the effectiveness of NCPB related to the site of primary pancreas cancer. The aim of the study was to assess the effectiveness of NCPB in pancreatic cancer pain, depending on the location of the pancreatic tumor.

Methods
The prospective study was conducted in 50 consecutive patients diagnosed with pancreatic cancer. The patients were categorized into two different groups depending on tumor localization: group 1: patients with the cancer of the head of the pancreas and group 2: patients with the cancer of the body and tail of the pancreas. The qualitative and quantitative pain analyses were performed before and after NCPB. The patients underwent prognostic celiac plexus block with bupivacaine, followed by neurolysis during fluoroscopic control within the next 24 h.

Results
After NCPB, 37 patients (74%) had effective pain relief during the first 3 months or until death. Of the 37 patients who had effective pain relief, 33 (92%) were from group 1 and 4 (29%) were from group 2. In the remaining 13 patients (3 patients from group 1 and 10 patients from group 2), pain relief after NCPB was not satisfactory. Those patients were scheduled for repeated retrocrural neurolysis during computed tomography control. Computed tomography showed massive growth of the tumor around the celiac axis with metastases. After repeated neurolysis, pain relief clinically still was not satisfactory, necessitating additional opioid treatment.

Conclusion
In this study, unilateral transcrural celiac plexus neurolysis has been shown to provide effective pain relief in 74% of patients with pancreatic cancer pain. Neurolysis was more effective in cases with tumor involving the head of the pancreas. In the cases with advanced tumor proliferation, regardless of the technique used, the analgesic effects of NCPB were not satisfactory.
Female Gender Associates with Increased Duration of Intubation and Length of Stay after Coronary Artery Surgery
Authors: Butterworth John , James Robert , Prielipp Richard , Cerese Julie , Livingston Jean , Burnett David 
Published: November 2003

Background
Females have worse outcome than do males after coronary artery bypass grafting; however, gender effects on length of stay (LOS) outcomes, such as duration of intubation or intensive care unit (ICU) LOS, have not been evaluated previously. The authors hypothesized that adjustment for pertinent preoperative covariates would eliminate any significant effect of gender on duration of intubation, LOS in the ICU after extubation, total ICU LOS, postoperative (exclusive of ICU) LOS, or total postoperative LOS.

Methods
Patients undergoing elective or urgent primary coronary artery bypass grafting surgery at 51 academic health centers in 1995 and 1997 were studied. Unique multivariable statistical models were developed for duration of intubation, ICU LOS after extubation, total ICU LOS, and postoperative (exclusive of ICU and total) LOS to test for independent associations with gender. Preoperative but not intraoperative or postoperative variables were included in the model. P> or =0.01 was considered significant.

Results
All LOSs were of significantly longer duration in females than in males in both the 1995 (n = 1,064) and 1997 (n = 910) data collections. After covariate adjustment, female sex remained associated with significantly longer duration ICU LOS and total postoperative LOS in both the 1995 (female:male ratios 1.30:1 and 1.13:1, respectively) and the 1997 (female:male ratios 1.19:1 and 1.12:1, respectively) data sets. After covariate adjustment, duration of intubation and ICU LOS after extubation were of significantly longer duration in women than men in 1995 (female:male ratios 1.22:1 and 1.39:1, respectively), but the differences were not significant in 1997.

Conclusions
Even in the context of accelerated recovery programs, these analyses show that female sex has powerful associations with increased LOS intervals for coronary artery bypass grafting surgery, even after adjustment for preoperative covariates. These effects could result from differences in the ways in which men and women respond to coronary artery disease, anesthesia, and coronary artery bypass grafting surgery, or to bias on the part of healthcare workers.
Efficacy of Two Methods for Reducing Postbypass Afterdrop
Authors: Rajek Angela , Lenhardt Rainer , Sessler Daniel I. , Brunner Gabriele , Haisjackl Markus , Kastner Johannes , Laufer Günther 
Published: November 2003

Background
Afterdrop, defined as the precipitous reduction in core temperature after cardiopulmonary bypass, results from redistribution of body heat to inadequately warmed peripheral tissues. The authors tested two methods of ameliorating afterdrop: (1) forced-air warming of peripheral tissues and (2) nitroprusside-induced vasodilation.

Methods
Patients were cooled during cardiopulmonary bypass to approximately 32 degrees C and subsequently rewarmed to a nasopharyngeal temperature near 37 degrees C and a rectal temperature near 36 degrees C. Patients in the forced-air protocol (n = 20) were assigned randomly to forced-air warming or passive insulation on the legs. Active heating started with rewarming while undergoing bypass and was continued for the remainder of surgery. Patients in the nitroprusside protocol (n = 30) were assigned randomly to either a control group or sodium nitroprusside administration. Pump flow during rewarming was maintained at 2.5 l x m(-2) x min(-1) in the control patients and at 3.0 l x m(-2) x min(-1) in those assigned to sodium nitroprusside. Sodium nitroprusside was titrated to maintain a mean arterial pressure near 60 mm Hg. In all cases, a nasopharyngeal probe evaluated core (trunk and head) temperature and heat content. Peripheral compartment (arm and leg) temperature and heat content were estimated using fourth-order regressions and integration over volume from 18 intramuscular needle thermocouples, nine skin temperatures, and "deep" hand and foot temperature.

Results
In patients warmed with forced air, peripheral tissue temperature was higher at the end of warming and remained higher until the end of surgery. The core temperature afterdrop was reduced from 1.2+/-0.2 degrees C to 0.5+/-0.2 degrees C by forced-air warming. The duration of afterdrop also was reduced, from 50+/-11 to 27+/-14 min. In the nitroprusside group, a rectal temperature of 36 degrees C was reached after 30+/-7 min of rewarming. This was only slightly faster than the 40+/-13 min necessary in the control group. The afterdrop was 0.8+/-0.3 degrees C with nitroprusside and lasted 34+/-10 min which was similar to the 1.1+/-0.3 degrees C afterdrop that lasted 44+/-13 min in the control group.

Conclusions
Cutaneous warming reduced the core temperature afterdrop by 60%. However, heat-balance data indicate that this reduction resulted primarily because forced-air heating prevented the typical decrease in body heat content after discontinuation of bypass, rather than by reducing redistribution. Nitroprusside administration slightly increased peripheral tissue temperature and heat content at the end of rewarming. However, the core-to-peripheral temperature gradient was low in both groups. Consequently, there was little redistribution in either case.