bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebellar Nitric Oxide Is Increased during Isoflurane Anesthesia Compared to Halothane Anesthesia
Authors: Loeb Alex L. , Raj Nichelle R. , Longnecker David E. 
Published: November 2003

Background
This study examined the influences of isoflurane versus halothane anesthesia on basal and agonist-stimulated nitric oxide in the cerebellum of intact rats. Nitric oxide was measured using the hemoglobin-trapping method in an in vivo microdialysis technique. This method uses the stoichiometric reaction of nitric oxide with oxyhemoglobin to produce methemoglobin and nitrate; the change in methemoglobin concentration is measured spectrophotometrically to estimate nitric oxide concentration.

Methods
Male Wistar rats were anesthetized with isoflurane (1.4%) or halothane (1.2%), mechanically ventilated and paralyzed (intravenous pancuronium, 1 mg/kg). Microdialysis probes were implanted into the cerebellum. Bovine oxyhemoglobin dissolved in artificial cerebrospinal fluid was pumped through the probe (2 microl/min) and assayed at 15-min intervals. The glutamatergic agonist, kainic acid (KA, 5 mg/kg, intraarterially), was used to stimulate nitric oxide production. NG-nitro L-arginine methyl ester (L-NAME, 40 mg/kg, intravenously) was used to inhibit nitric oxide synthase.

Results
Unstimulated cerebellar nitric oxide concentrations were stable and greater during anesthesia with isoflurane (532+/-31 nM; mean +/- SEM) than with halothane (303+/-23 nM). L-NAME pretreatment reduced nitric oxide concentrations during isoflurane, but not halothane, anesthesia. Infusion of KA increased nitric oxide in both groups; however, the increase in nitric oxide was significantly greater during isoflurane anesthesia. Pretreatment with L-NAME inhibited the response to KA in both groups.

Conclusions
Nitric oxide production in the cerebellum, monitored by microdialysis, was greater during isoflurane anesthesia than during halothane anesthesia. Increased nitric oxide production during isoflurane anesthesia would be expected to impact central neuronal function and cerebral blood flow and vascular resistance.
Mechanisms of Isoflurane-increased Submaximum Ca2+-activatedForce in Rabbit Skinned Femoral Arterial Strips
Authors: Toda Hiroshi , Su Judy Y. 
Published: November 2003

Background
Isoflurane enhances contraction in isolated intact arterial rings by a protein kinase C (PKC) activator and also causes contracture in skinned arterial strips. This study investigated the mechanisms of this isoflurane activation of the contractile proteins of skinned strips.

Methods
The skinned strips, mounted on photodiode force transducers, were prepared from rabbit femoral arteries treated with saponin. The strips were activated by 1 microM Ca2+ (buffered with 7 mM EGTA) with or without inhibitors for PKC and calmodulin-dependent protein kinase II (CaM kinase II). When force reached steady state, isoflurane was administered and changes in force were observed. Another group of the strips was frozen to assay myosin light chain phosphorylation (MLC-p) using two-dimensional electrophoresis and immunoblotting. Analysis of variance was used to compare the results from test and control groups. Probability values <0.05 were significant.

Results
Isoflurane (1-5%) dose dependently increased (24-81%) the Ca2+-activated force. At 1% and 5% isoflurane, MLC-p did not change either as the force increased or reached a new steady state level. However, with 3% isoflurane, MLC-p transiently decreased (29.1% and 17.1% of total MLC for 0% and 3% isoflurane, respectively). The 3% isoflurane-increased force was blocked by 10 microM bisindolymaleidmide, an inhibitor of PKC, but not by 10 microM Gö-6976, an inhibitor of Ca2+-dependent PKC, and was enhanced 50% by 0.1 mM KN-62, an inhibitor of CaM kinase II.

Conclusions
Isoflurane increased submaximum Ca2+-activated force in skinned femoral arterial strips by activating Ca2+-independent PKC, possibly epsilon isoezyme. The isoflurane-decreased MLC-p may be caused by activation of CaM kinase II.
Dexmedetomidine Produces Similar Alterations in the Determinants of Left Ventricular Afterload in Conscious Dogs before and after the Development of Pacing-induced Cardiomyopathy
Authors: Pagel Paul S. , Hettrick Douglas A. , Kersten Judy R. , Warltier David C. 
Published: November 2003

Background
The authors tested the hypothesis that intravenous dexmedetomidine produces alterations in left ventricular (LV) afterload that are deleterious to cardiac performance in conscious dogs with pacing-induced cardiomyopathy.

Methods
Dogs (n = 8) were fitted with instruments for long-term measurement of LV and aortic blood pressure, aortic blood flow, and subendocardial segment length and received dexmedetomidine (1.25, 2.5, and 5 microg/kg) in a cumulative manner before and after 19+/-3 (mean +/- SEM) days of rapid LV pacing. LV afterload was measured with aortic input impedance [Zin(omega)] and quantified with a three-element Windkessel model. Hemodynamics and Zin(omega)) were assessed under control conditions and 5 and 60 min after administration of each dose.

Results
Dexmedetomidine caused early and late decreases in heart rate, the maximum rate of increase of LV pressure, mean aortic blood flow, and stroke volume in dogs before and after pacing. Dexmedetomidine caused similar early increases in total arterial resistance and decreases in total arterial compliance in dogs before and after pacing. Early dexmedetomidine-induced increases in resistance and decreases in compliance caused similar reductions in mean aortic blood flow in cardiomyopathic compared with healthy dogs. Resistance and compliance returned to control values, and characteristic aortic impedance decreased late after dexmedetomidine in healthy dogs. In contrast, resistance remained elevated late after dexmedetomidine in dogs with dilated cardiomyopathy.

Conclusions
Dexmedetomidine causes similar alterations in hemodynamics and LV afterload in conscious dogs with and without pacing-induced cardiomyopathy.
Effects of Respiratory Alkalosis and Acidosis on Myocardial Blood Flow and Metabolism in Patients with Coronary Artery Disease
Authors: Kazmaier Stephan , Weyland Andreas , Buhre Wolfgang , Stephan Heidrun , Rieke Horst , Filoda Klaus , Sonntag Hans 
Published: November 2003

Background
Variation of the arterial carbon dioxide partial pressure (PaCO2) is not uncommon in anesthetic practice. However, little is known about the myocardial consequences of respiratory alkalosis and acidosis, particularly in patients with coronary artery disease. The aim of the current study was to investigate the effects of variation in PaCO2 on myocardial blood flow (MBF), metabolism, and systemic hemodynamics in patients before elective coronary artery bypass graft surgery.

Methods
In 10 male anesthetized patients, measurements of MBF, myocardial contractility, metabolism, and systemic hemodynamics were made in a randomized sequence at PaCO2 levels of 30, 40, and 50 mmHg, respectively. The MBF was measured using the Kety-Schmidt technique with argon as a tracer. End-diastolic left ventricular pressure and the maximal increase of left ventricular pressure were assessed using a manometer-tipped catheter.

Results
The cardiac index significantly changed with varying PaCO2 levels (hypocapnia, - 9%; hypercapnia, 13%). This reaction was associated with inverse changes in systemic vascular resistance index levels. The MBF significantly increased by 15% during hypercapnia, whereas no change was found during hypocapnia. Myocardial oxygen and glucose uptake and the maximal increase of left ventricular pressure were not affected by varying PaCO2 levels.

Conclusions
In anesthetized patients with coronary artery disease, short-term variations in PaCO2 have significant effects on MBF but do not influence global myocardial oxygen and glucose uptake. Changes in systemic hemodynamics associated with respiratory alkalosis and acidosis are caused by changes in systemic vascular resistance rather than by alterations in myocardial contractility.
Antiemetic Activity of Propofol after Sevoflurane and Desflurane Anesthesia for Outpatient Laparoscopic Cholecystectomy
Authors: Song Dajun , Whitten Charles W. , White Paul F. , Yu Song Y. , Zarate Eduardo 
Published: November 2003

Background
Controversy exists regarding the effectiveness of propofol to prevent postoperative nausea and vomiting. This prospective, randomized, single-blinded study was designed to evaluate the antiemetic effectiveness of 0.5 mg/kg propofol when administered intravenously after sevoflurane- compared with desflurane-based anesthesia.

Methods
Two hundred fifty female outpatients undergoing laparoscopic cholecystectomy were assigned randomly to one of four treatment groups. All patients were induced with intravenous doses of 2 mg midazolam, 2 microg/kg fentanyl, and 2 mg/kg propofol and maintained with either 1-4% sevoflurane (groups 1 and 2) or 2-8% desflurane (groups 3 and 4) in combination with 65% nitrous oxide in oxygen. At skin closure, patients in groups 1 and 3 were administered 5 ml intravenous saline, and patients in groups 2 and 4 were administered 0.5 mg/kg propofol intravenously. Recovery times were recorded from discontinuation of anesthesia to awakening, orientation, and readiness to be released home. Postoperative nausea and vomiting and requests for antiemetic rescue medication were evaluated during the first 24 h after surgery.

Results
Propofol, in an intravenous dose of 0.5 mg/kg, administered at the end of a sevoflurane-nitrous oxide or desflurane-nitrous oxide anesthetic prolonged the times to awakening and orientation by 40-80% and 25-30%, respectively. In group 2 (compared with groups 1, 3, and 4), the incidences of emesis (22% compared with 47%, 53%, and 47%) and requests for antiemetic rescue medication (19% compared with 42%, 50%, and 47%) within the first 6 h after surgery were significantly lower, and the time to home-readiness was significantly shorter in duration (216 +/- 50 min vs. 249 +/- 49 min, 260 +/- 88 min, and 254 +/- 72 min, respectively).

Conclusions
A subhypnotic intravenous dose of propofol (0.5 mg/kg) administered at the end of outpatient laparoscopic cholecystectomy procedures was more effective in preventing postoperative nausea and vomiting after a sevoflurane-based (compared with a desflurane-based) anesthetic.
Combined Intravenous Lidocaine and Inhaled Salbutamol Protect against Bronchial Hyperreactivity More Effectively than Lidocaine or Salbutamol Alone
Authors: Groeben Harald , Silvanus Marie-Theres , Beste Mechthild , Peters Jurgen 
Published: November 2003

Background
Airway instrumentation in persons with asthma is linked to the risk of life-threatening bronchospasm. To attenuate the response to airway irritation, intravenous lidocaine is recommended (based on animal experiments) and mitigates the response to histamine inhalation in asthmatic volunteers. However, the effects of lidocaine have not been compared with standard prophylaxis with beta-sympathomimetic aerosols. Therefore, the effect of lidocaine, salbutamol, combined treatment, and placebo control were tested in awake volunteers with bronchial hyperreactivity.

Methods
After approval from the local ethics committee, 15 persons, who were selected because they showed a decrease in forced expiratory volume in 1 s (FEV1) more than 20% of baseline in response to inhaled histamine in a concentration less than 18 mg/ml (PC20), were enrolled in a placebo-controlled, double-blind, and randomized study. The challenge was repeated on four different days and the volunteers were pretreated with either intravenous lidocaine, inhalation of salbutamol, inhalation of salbutamol plus intravenous lidocaine, or placebo. Lidocaine plasma concentrations were also measured. Statistical analyses included the Friedman test and Wilcoxon's rank sum.

Results
The baseline PC20 was 6.4 +/- 4.3 mg/ml. Intravenous lidocaine and salbutamol aerosol both significantly increased the histamine threshold to 14.2 +/- 9.5 mg/ml and 16.8 +/- 10.9 mg/ml, respectively (mean +/- SD). However, the combination of lidocaine and salbutamol significantly increased the PC20 even further to 30.7 +/- 15.7 mg/ml than did salbutamol or lidocaine alone.

Conclusions
In volunteers with bronchial hyperreactivity, both lidocaine and salbutamol attenuate the response to an inhalational histamine challenge, and their combined administration has much greater effects than does either drug alone. Accordingly, pretreatment of patients with bronchial hyperreactivity with both beta-mimetic aerosol and intravenous lidocaine is recommended before airway irritation.
Non-thermoregulatory Shivering in Patients Recovering from Isoflurane or Desflurane Anesthesia
Authors: Horn Ernst-Peter , Sessler Daniel I. , Standl Thomas , Schroeder Frank , Bartz Hans-Jurgen , Beyer Juan Carlos , Schulte am Esch Jochen 
Published: November 2003

Background
Although cold-induced shivering is an obvious source of postanesthetic tremor, other causes may contribute. Consistent with this theory, the authors had previously identified an abnormal clonic component of postoperative shivering and proposed that it might be nonthermoregulatory. A subsequent study, however, failed to identify spontaneous muscular activity in normothermic volunteers. These data suggested that the initial theory was erroneous or that a yet-to-be identified factor associated with surgery might facilitate shivering in patients after operation. Therefore, the authors tested the hypothesis that some postoperative tremor is nonthermoregulatory.

Methods
One hundred twenty patients undergoing major orthopedic operation were observed. They were grouped randomly to receive maintenance anesthesia with nitrous oxide and isoflurane (0.8 +/- 0.4%) or desflurane (3.4 +/- 1.1%). Twenty patients in each group were allowed to become hypothermic, whereas normal body temperatures were maintained in the others (tympanic membrane temperature exceeding preinduction values). Arteriovenous shunt vasoconstriction was evaluated using forearm-minus-fingertip skin-temperature gradients; gradients less than 0 degrees C identified vasodilation. Postanesthetic shivering was graded by a blinded investigator. Tremor in patients who were normothermic and vasodilated was considered nonthermoregulatory.

Results
Thermoregulatory responses were similar after isoflurane or desflurane anesthesia. Approximately 50% of the unwarmed patients shivered. Shivering was observed in 27% of the patients who were normothermic; 55% of this spontaneous muscular activity occurred in vasodilated patients. Among the normothermic patients, 15% fulfilled the authors' criteria for nonthermoregulatory tremor.

Conclusions
The incidence of postoperative shivering is inversely related to core temperature. Therefore, it was not surprising that shivering was most common among the hypothermic patients. The major findings, however, were that shivering remained common even among patients who were kept scrupulously normothermic and that many shivered while they were vasodilated. Thus, postoperative patients differ from nonsurgical volunteers in demonstrating a substantial incidence of nonthermoregulatory tremor.
Prospective, Randomized Comparison of Deep or Superficial Cervical Plexus Block for Carotid Endarterectomy Surgery
Authors: Stoneham Mark D. , Doyle Anthony R. , Knighton John D. , Dorje Pema , Stanley James C. 
Published: November 2003

Background
Carotid endarterectomy may be performed under cervical plexus block with local anesthetic supplementation by the surgeon as necessary during surgery. It is unclear, however, whether deep or superficial cervical plexus block offers the best operating conditions or patient satisfaction. Therefore, the authors compared the two in patients undergoing carotid endarterectomy.

Methods
Forty patients undergoing carotid endarterectomy were randomized to receive either a superficial or a deep cervical plexus block with 20 ml bupivacaine, 0.375%. Outcomes subjected to statistical analysis included supplemental anesthetic supplementation with lidocaine, 1%, by the surgeon, dermatomes affected by the block, paresthesia during block placement, postoperative pain scores, and analgesic requirements.

Results
Median supplemental lidocaine requirements were 6 ml (range, 0.5 to 20 ml) in the deep block group and 6 ml (range, 0 to 20 ml) in the superficial block group (P = 0.7323). Patients in the deep block group who reported paresthesia during block placement required less lidocaine supplementation (median, 2; range, 0.5 to 20 ml) than the 9.5 ml (range, 6 to 15.5 ml) required by those who did not experience paresthesia (P = 0.0113). Compared with patients in the superficial block group, those in the deep block group were less likely to need analgesia in the first 24 h after operation (P = 0.047), and those who required analgesia received it later (6.6 +/- 4.1 vs. 3.9 +/- 1.4 h after operation; Student's t test, P = 0.02). One patient in each group expressed dissatisfaction with the technique.

Conclusions
Carotid endarterectomy may be performed satisfactorily during superficial or deep cervical plexus block placement with no differences in terms of supplemental local anesthetic requirements, although this is influenced by whether paresthesia is elicited during placement of the deep block. Therefore, the clinician's decision to use one block rather than another need not be based on any assumed superiority of one block based on intraoperative conditions or patient satisfaction.
Effects of Intravenous General Anesthetics on [(3) H]GABA Release from Rat Cortical Synaptosomes
Authors: Murugaiah Kamala D. , Hemmings Hugh C. 
Published: November 2003

Background
Potentiation by general anesthetics of gamma-aminobutyric acid (GABA)-mediated inhibitory transmission in the central nervous system is attributed to GABA(A) receptor-mediated postsynaptic effects. However, the role of presynaptic mechanisms in general anesthetic action is not well characterized, and evidence for anesthetic effects on GABA release is controversial. The effects of several intravenous general anesthetics on [3H]GABA release from rat cerebrocortical synaptosomes (isolated nerve terminals) were investigated.

Methods
Purified synaptosomes were preloaded with [3H]GABA and superfused with buffer containing aminooxyacetic acid and nipecotic acid to inhibit GABA metabolism and reuptake, respectively. Spontaneous and elevated potassium chloride depolarization-evoked [3H]GABA release were evaluated in the superfusate in the absence or presence of various anesthetics, extracellular Ca2+, GABA receptor agonists and antagonists, and 2,4-diaminobutyric acid.

Results
Propofol, etomidate, pentobarbital, and alphaxalone, but not ketamine, potentiated potassium chloride-evoked [3H]GABA release (by 1.3 to 2.9 times) in a concentration-dependent manner, with median effective concentration values of 5.4 +/- 2.8 microM (mean +/- SEM), 10.1 +/- 2.1 microM, 18.8 +/- 5.8 microM, and 4.4 +/- 2.0 microM. Propofol also increased spontaneous [3H]GABA release by 1.7 times (median effective concentration = 7.1 +/- 3.4 microM). Propofol facilitation of [3H]GABA release was Ca2+ dependent and inhibited by bicuculline and picrotoxin, but was insensitive to pretreatment with 2,4-diaminobutyric acid, which depletes cytoplasmic GABA pools.

Conclusions
Low concentrations of propofol, etomidate, pentobarbital, and alphaxalone facilitated [3H]GABA release from cortical nerve terminals. General anesthetics may facilitate inhibitory GABA-ergic synaptic transmission by a presynaptic mechanism in addition to their well-known postsynaptic actions.
Mechanistic Aspects of Carbon Monoxide Formation from Volatile Anesthetics
Authors: Baxter Pamela J. , Garton Kyle , Kharasch Evan D. 
Published: November 2003

Background
Desflurane, enflurane and isoflurane can be degraded to carbon monoxide (CO) by carbon dioxide absorbents, whereas sevoflurane and halothane form negligible amounts of CO. Carbon monoxide formation is greater with drier absorbent, and with barium hydroxide, than with soda lime. The mechanism, role of absorbent composition and water, and anesthetic structures determining CO formation are unknown. This investigation examined sequential steps in anesthetic degradation to CO.

Methods
Carbon monoxide formation from anesthetics and desiccated barium hydroxide lime or soda lime was determined at equimole and equiMAC concentrations. Carbon monoxide formation from deuterium-substituted anesthetics was also quantified. Proton abstraction from anesthetics by strong base was determined by deuterium isotope exchange. A reactive chemical intermediate was trapped and identified by gas chromatography-mass spectrometry. The source of the oxygen in CO was identified by 18O incorporation.

Results
Desflurane,enflurane,andisoflurane(difluoromethylethyl ethers), but not sevoflurane (monofluoromethyl ether), methoxyflurane (methy-ethyl ether), or halothane (alkane) were degraded to CO. The amount of CO formed was desflurane > or = enflurane > isoflurane at equiMAC and enflurane > desflurane > isoflurane at equimole concentrations. Proton abstraction from the difluoromethoxy carbon was greater with potassium than with sodium hydroxide, but unmeasurable with barium hydroxide. Carbon monoxide formation was correlated (r = 0.95-1.00) with difluoromethoxy (enflurane > desflurane > isoflurane > or = methoxyflurane = sevoflurane = 0) but not ethyl carbon proton abstraction. Deuterium substitution on enflurane and desflurane diminished CO formation. Chemical trapping showed formation of a difluorocarbene intermediate from enflurane and desflurane. Incorporation of H2(18)O in barium hydroxide lime resulted in C18O formation from unlabeled enflurane and desflurane.

Conclusions
A difluoromethoxy group is a structural requirement for haloether degradation to CO. Results are consistent with initial base-catalyzed difluoromethoxy proton abstraction (potassium > sodium hydroxide, thus greater CO formation with barium hydroxide lime vs. soda lime) forming a carbanion (reprotonated by water to regenerate the anesthetic, hence requirements for relatively dry absorbent), carbanion decomposition to a difluorocarbene, and subsequent difluorocarbene reaction to form CO.
Prolonged Intercostal Nerve Blockade in Sheep Using Controlled-release of Bupivacaine and Dexamethasone from Polymer Microspheres
Authors: Drager Christiane , Benziger David , Gao Feng , Berde Charles B. 
Published: November 2003

Background
Previous work from the authors' group characterized a prolonged percutaneous blockade of the sciatic nerve in rats using bupivacaine-dexamethasone microspheres. The goals of the current study are to examine the (1) efficacy of bupivacaine microspheres with and without dexamethasone for intercostal blockade in sheep; (2) scaling of dose and duration with a 100-fold increase in body size from rats to sheep; (3) local toxicity and adverse systemic reactions to bupivacaine microspheres with and without dexamethasone.

Methods
Intercostal blocks were performed percutaneously in sedated sheep. Sensory blockade was measured at repeated time points by absent flinch response to skin pinch. Plasma bupivacaine concentrations were measured using high performance liquid chromatography. Chest wall specimens were examined by light microscopy.

Results
The duration of intercostal blockade increased with bupivacaine dose for animals receiving from 8 to 80 mg/kg of microspheres with and without dexamethasone. At each dose, microspheres containing dexamethasone had a longer duration of block than microspheres without dexamethasone. From 8 to 80 mg/kg, the mean duration of block with bupivacaine-dexamethasone microspheres increased from 4 to 13 days. Plasma concentrations of bupivacaine remained 10-fold below the convulsive EC50 concentration for sheep. Chest wall histology showed a significant granulomatous reaction around bupivacaine microspheres but not around bupivacaine-dexamethasone microspheres.

Conclusions
A single administration of bupivacaine-dexamethasone microspheres produces an effective chest wall analgesia of several days' duration. This may prove useful clinically for thoracic surgery or trauma.