bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition by Volatile Anesthetics of Endogenous Glutamate Release from Synaptosomes by a Presynaptic Mechanism
Authors: Schlame Michael , Hemmings Hugh C. Jr. 
Published: November 2003

Background
Synaptic transmission is more sensitive than axonal conduction to the effects of general anesthetics. Previous studies of the synaptic effects of general anesthetics have focused on postsynaptic sites of action. We now provide direct biochemical evidence for a presynaptic effect of volatile anesthetics on neurotransmitter release.

Methods
Rat cerebrocortical synaptosomes (isolated presynaptic nerve terminals) were used to determine the effects of general anesthetics on the release of endogenous L-glutamate, the major fast excitatory neurotransmitter. Basal and evoked (by 4-aminopyridine, veratridine, increased KCl, or ionomycin) glutamate release were measured by continuous enzyme-coupled fluorometry.

Results
Clinical concentrations of volatile halogenated anesthetics, but not of pentobarbital, inhibited 4-aminopyridine-evoked Ca(2+)-dependent glutamate release. Halothane also inhibited veratridine-evoked glutamate release but not basal, KCl-evoked, or ionomycin-evoked glutamate release. Halothane inhibited both the 4-aminopyridine-evoked and the KCl-evoked increase in free intrasynaptosomal [Ca2+].

Conclusions
Inhibition of glutamate release from presynaptic nerve terminals is a potential mechanism of volatile anesthetic action. Comparison of the sensitivity of glutamate release evoked by secretogogues that act at various steps in the neurotransmitter release process suggests that halothane does not affect Ca(2+)-secretion coupling or vesicle exocytosis but inhibits glutamate release at a step proximal to Ca2+ influx, perhaps by blocking presynaptic Na+ channels. Synaptosomal glutamate release evoked by 4-aminopyridine should provide a useful system for further characterization of the presynaptic effects of anesthetics.
Regulation of Norepinephrine Release by β2-Adrenergic Receptors during Halothane Anesthesia
Authors: Deegan Robert , He Huai Bing , Krivoruk Yuri , Wood Alastair , Wood Margaret 
Published: November 2003

Background
Presynaptic receptors control norepinephrine (NE) release. It has been hypothesized that epinephrine stimulates prejunctional beta 2-adrenergic receptors to facilitate NE release from sympathetic nerve endings, and therefore, presynaptic receptors controlling NE release are potential therapeutic targets to limit the adverse effects of excess sympathetic stimulation during anesthesia. We have previously demonstrated beta 2-adrenergic receptor-augmented release of NE in the human forearm and have shown that halothane inhibits sympathetic activity in vivo by decreasing the NE spillover rate into plasma. The goal of the current study was to determine the effect of halothane on beta 2-adrenergic receptor-augmented NE release in a canine hind-limb experimental model.

Methods
Seven female dogs were studied awake and during halothane anesthesia (1.0 minimum alveolar concentration). A trace dosage of [3H]NE (15 microCi over a 1-min period and 0.6 microCi/min thereafter) was infused into the femoral vein. Before and during femoral arterial administration of isoproterenol at two dosages (30 and 80 mg/min), hind-limb blood flow was measured by an ultrasonic flow probe and hind-limb NE spillover by an isotope dilutional technique.

Results
In awake dogs, isoproterenol significantly increased hind-limb blood flow and NE spillover into the hind limb. Halothane had no effect on baseline or isoproterenol-stimulated hind-limb blood flow (a postjunctional beta 2 effect) but significantly inhibited the isoproterenol-induced increase in hind-limb NE spillover (a prejunctional beta 2 effect).

Conclusions
The isoproterenol-mediated increase in NE release is inhibited by halothane anesthesia, indicating that halothane inhibits prejunctional beta 2-adrenergic receptor regulation of NE release.
A Subtype of α1Adrenoceptor Mediates Depression of Conduction in Purkinje Fibers Exposed to Halothane
Authors: Turner Lawrence A. , Vodanovic Sanja , Hoffmann Raymond G. , Kampine John P. , Bosnjak Zeljko J. 
Published: November 2003

Background
An action of epinephrine at alpha adrenoceptors has been reported to slow conduction in Purkinje fibers exposed to halothane. In Purkinje fibers one pharmacologically distinguishable alpha 1-adrenoceptor subtype (alpha 1B) sensitive to the noncompetitive antagonist chloroethylcholinidine mediates decreases in automaticity. Another alpha 1 subtype (alpha 1A), sensitive to the competitive antagonist WB4101, increases spontaneous rate and action potential duration by a mechanism thought to involve hydrolysis of membrane phosphoinositides by phospholipase C. This study examined the dose-response relation and receptor-effector mechanisms underlying depression of conduction in canine Purkinje fibers by epinephrine with halothane.

Methods
Conduction velocity was determined in vitro by measuring the conduction time between action potentials recorded from two Purkinje fibers located about 6 mm apart along the length of free running portions of the ventricular conduction system, the false tendons. Velocity was evaluated at 1-min intervals during trials of rapid exposure to different agonists in groups of 6-12 preparations.

Results
Epinephrine (0.2-5.0 microM) transiently decreased Purkinje conduction velocity in a dose-related manner by as much as 33% (at 5 microM epinephrine with 0.86 mM (2.8%) halothane). Velocity decreased by 5% (P < or = 0.01) at an epinephrine concentration similar to "just-threshold" dysrhythmogenic plasma epinephrine concentrations (0.2 microM epinephrine with 0.46 mM halothane) reported in halothane-anesthetized dogs. The decreases of conduction velocity were blocked by prazosin but not by metoprolol, were produced by phenylephrine but not by clonidine, and were antagonized by equimolar (0.5 microM) concentrations of WB4101 more so (P < or = 0.01) than by chloroethylclonidine. WB4101 (0.1 microM) produced 87% inhibition of the response to 0.2 microM epinephrine after chloroethylclonidine pretreatment, indicating mediation by the alpha 1A subtype. Other agonists linked to cardiac phospholipase C activation, including endothelin 1 (40 nM) and the muscarinic agonist carbamylcholine (1 mM), also decreased conduction velocity in fibers exposed to halothane.

Conclusions
Clinically relevant concentrations of epinephrine transiently depress conduction in Purkinje fibers exposed to halothane by activating cardiac alpha 1 adrenoceptors, largely but not exclusively the WB4101-sensitive alpha 1A subtype, reportedly coupled to stimulation of phospholipase C and generation of the second messengers diacylglycerol and inositol trisphosphate. Anesthetic potentiation of cardiac alpha 1-adrenoceptor effects may contribute to the generation of halothane-epinephrine dysrhythmias by abnormally slowing conduction and facilitating reentry.
The Pharmacodynamic Interaction of Propofol and Alfentanil during Lower Abdominal Surgery in Women
Authors: Vuyk Jaap , Lim Toine , Engbers Frank H. M. , Burm Anton G. L. , Vletter Arie A. , Bovill James G. 
Published: November 2003

Background
Propofol and alfentanil are frequently combined to provide general anesthesia. The purpose of this study was to characterize the pharmacodynamic interaction between propofol and alfentanil for several clinically relevant end points.

Methods
Twenty-one women, aged 20-55 yr, scheduled for lower abdominal surgery, were randomly assigned in a double-blind manner to one of three groups to receive a computer-controlled infusion of propofol with target concentrations of 2, 4, or 6 micrograms/ml. In addition, all patients received computer-controlled infusion of alfentanil (initial target concentration 50 ng/ml). While the target concentration of propofol was maintained constant, the target concentration of alfentanil was varied in steps of 10-50 ng/ml according to the presence or absence of patient responses to perioperative stimuli. Arterial blood samples for alfentanil and propofol determination were taken at clinically relevant stimuli. Alfentanil-propofol interactions for laryngoscopy, intubation, skin incision, the opening of the peritoneum, and awakening were determined by logistic regression over the three groups (n = 21). The alfentanil concentrations associated with a 50% probability (EC50s) of suppression of responses to intraabdominal surgical stimuli, as determined by logistic regression in the individual patients, were related to corresponding mean blood propofol concentrations by nonlinear regression analysis.

Results
With blood propofol concentrations increasing from 2 to 10 micrograms/ml, the EC50 of alfentanil decreased from 170 to 25 ng/ml for laryngoscopy, from 280 to 23 ng/ml for intubation, from 259 to 9 ng/ml for the opening of the peritoneum, and from 209 to 16 ng/ml for the intraabdominal surgical stimuli. With plasma alfentanil concentrations increasing from 10 to 150 ng/ml, the EC50 of propofol for the regaining of consciousness decreased from 3.8 to 0.8 microgram/ml.

Discussion
We defined the pharmacodynamic interaction between propofol and alfentanil for suppression of responses to perioperative stimuli during lower abdominal surgery. We conclude that propofol reduces alfentanil requirements for all studied clinical end points. In addition, alfentanil decreases propofol concentrations at which patients regain consciousness.
Inhibition of Platelet Aggregation by Inhaled Nitric Oxide in Patients with Acute Respiratory Distress Syndrome
Authors: Samama Charles Marc , Diaby Mohamed , Fellahi Jean-Luc , Mdhafar Ayoub , Eyraud Daniel , Arock Michel , Guillosson Jean-Jacques , Coriat Pierre , Rouby Jean-Jacques 
Published: November 2003

Background
Nitric oxide inhibits platelet adhesion and aggregation in vitro. The aim of this prospective study was to assess the platelet antiaggregating activity of nitric oxide administered to patients with acute respiratory distress syndrome (ARDS) at increasing concentrations.

Methods
In six critically ill patients (mean age 37 +/- 16 yr) with ARDS (lung injury severity score > or = 2.2), the lungs were mechanically ventilated with inhaled nitric oxide (1, 3, 10, 30, and 100 ppm) randomly administered. Patients with cardiac dysrhythmias, septic shock, an underlying hemostasis disorder (constitutive or acquired), a platelet count less than 100 Giga/l, or a decreased platelet aggregation and those treated with antiplatelet or anticoagulant agents were excluded. Platelet aggregation was measured without nitric oxide and at each nitric oxide concentration in platelet-rich plasma issued from radial artery. Ivy bleeding time using a horizontal incision was simultaneously performed.

Results
After nitric oxide, a non-dose-dependent but statistically significant decrease in ex vivo platelet aggregation induced by three aggregating agents was observed: adenosine diphosphate = -56 +/- 18%, collagen = -37 +/- 18%, and ristocetin = -45 +/- 18% (P < 0.05). In each individual, Ivy bleeding time remained within normal values measured in healthy volunteers, and variations after nitric oxide did not correlate with changes in platelet aggregation. Simultaneously, arterial oxygenation improved significantly and pulmonary artery pressure decreased significantly.

Conclusions
In patients with ARDS and without preexisting coagulation disorders, the beneficial effects of inhaled nitric oxide on arterial oxygenation and pulmonary circulation are associated with a significant inhibition of platelet aggregation. This antithrombotic effect is not associated with a significant prolongation of the bleeding time.
Dynamic and Static Cerebral Autoregulation during Isoflurane, Desflurane, and Propofol Anesthesia
Authors: Strebel Stephan , Lam Arthur , Matta Basil , Mayberg Teresa S. , Aaslid Rune , Newell David W. 
Published: November 2003

Background
Although inhalation anesthetic agents are thought to impair cerebral autoregulation more than intravenous agents, there are few controlled studies in humans.

Methods
In the first group (n = 24), dynamic autoregulation was assessed from the response of middle cerebral artery blood flow velocity (Vmca) to a transient step decrease in mean arterial blood pressure (MABP). The transient hypotension was induced by rapid deflation of thigh cuffs after inflation for 3 min. In the second group (n = 18), static autoregulation was studied by observing Vmca in response to a phenylephrine-induced increase in MABP. All patients were studied during fentanyl (3 micrograms.kg-1.h-1)/nitrous oxide (70%) anesthesia, followed by, in a randomized manner, isoflurane, desflurane, or propofol in a low dose (0.5 MAC or 100 micrograms.kg-1.min-1) and a high dose (1.5 MAC or 200 micrograms.kg-1.min-1). The dynamic rate of regulation (dROR) was assessed from the rate of change in cerebrovascular resistance (MABP/Vmca) with the blood pressure decreases using computer modeling, whereas the static rate of regulation (sROR) was assessed from the change in Vmca with the change in MABP.

Results
Low-dose isoflurane delayed (dROR decreased) but did not reduce the autoregulatory response (sROR intact). Low-dose desflurane decreased both dROR and sROR. During 1.5 MAC isoflurane or desflurane, autoregulation was ablated (both dROR and sROR impaired). Neither dROR nor sROR changed with low- or high-dose propofol.

Conclusions
At 1.5 MAC, isoflurane and desflurane impaired autoregulation whereas propofol (200 micrograms.kg-1.min-1) preserved it.
The Effect of Neostigmine on Twitch Tension and Muscle Relaxant Concentration during Infusion of Mivacurium or Vecuronium
Authors: Szenohradszky Janos , Lau Marie , Brown Ronald , Sharma Manohar L. , Fisher Dennis M. 
Published: November 2003

Background
An investigation suggested that neostigmine may not effectively antagonize mivacurium, presumably because neostigmine impairs mivacurium's metabolism. However, the effect of neostigmine on mivacurium's metabolism in vivo has not been reported. Therefore, the effect of neostigmine on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion was determined.

Methods
Mivacurium was infused in five patients to maintain 90% depression of adductor pollicis twitch tension, then 50 micrograms/kg intravenous neostigmine was administered without altering the mivacurium infusion. Peak twitch tension after neostigmine, plasma cholinesterase activity, and mivacurium concentrations before and after neostigmine were measured. Five additional patients were given 50 micrograms/kg neostigmine to antagonize block due to continuous infusions of vecuronium.

Results
Neostigmine produced less antagonism of mivacurium (39 +/- 11%) than of vecuronium (54 +/- 9%, P < 0.05). Neostigmine decreased plasma cholinesterase activity and increased plasma concentrations of the trans-trans and cis-trans stereoisomers of mivacurium (P < 0.05).

Conclusions
Neostigmine is less effective at antagonizing the neuromuscular effect of mivacurium than that of vecuronium during constant infusion. Neostigmine increases plasma mivacurium concentrations, likely explaining its limited efficacy. Our results confirm that neostigmine impairs the metabolism of mivacurium in vivo and may explain the observation that neostigmine may not effectively antagonize mivacurium-induced block.
Neurocirculatory Responses to Sevoflurane in Humans
Authors: Ebert Thomas J. , Muzi Michael , Lopatka Craig W. 
Published: November 2003

Background
Sevoflurane and desflurane are new volatile anesthetics with low blood solubilities that confer properties of rapid anesthetic induction and emergence. Desflurane has been associated with neurocirculatory excitation after the rapid increase in inspired concentrations. The current study evaluated and compared the sympathetic and hemodynamic responses associated with the administration of sevoflurane to those associated with administration of desflurane in humans.

Methods
After Institutional Review Board approval, 21 healthy, young (19-32 yr) volunteers were randomly selected for participation. Arterial and central venous pressures were measured directly, and heart rate, forearm blood flow, and plasma norepinephrine concentrations were determined indirectly. Efferent muscle sympathetic nerve activity was recorded by microneurography. After neurocirculatory recordings at conscious baseline, measurements were repeated beginning 2 min after 2 mg/kg propofol while the anesthetic was increased incrementally by mask over a 10-min period at 1%, 2%, and 3% sevoflurane (n = 12) or 3%, 6%, and 9% desflurane (n = 9). Responses to intubation were recorded and, 20 min later, recordings were evaluated during steady-state periods of 0.41, 0.83, and 1.24 MAC. Data also were obtained after steady-state 0.83 MAC measurements when the inspired gas concentration was rapidly increased to either 3% sevoflurane or 9% desflurane ("transition" to 1.24 MAC).

Results
Neurocirculatory variables did not differ between the two groups at conscious baseline. During the period of administration via mask and during the "transition" period, the significant increases in sympathetic nerve activity, heart rate, mean arterial pressure, and central venous pressure associated with desflurane were not observed with sevoflurane. Ten minutes after induction, mean arterial pressure and heart rate responses to intubation did not differ between groups. With increasing anesthetic concentration, there were progressive and similar decreases in mean arterial pressure in both groups and no changes in heart rate. Central venous pressure, sympathetic nerve activity, and plasma norepinephrine increased with the greater minimum alveolar concentration multiple of desflurane but not with that of sevoflurane.

Conclusions
The neurocirculatory excitation seen with rapid increases in desflurane did not occur with sevoflurane. At steady-state, increasing the concentration of sevoflurane was associated with lower sympathetic nerve activity and central venous pressure and similar mean arterial pressure and heart rate with that of desflurane.
Local Anesthetic Test Dose as a Predictor of Effective Epidural Opioid Analgesia
Authors: Weitz Sandra R. , Drasner Kenneth 
Published: November 2003

Background
When local anesthetic is used to produce epidural anesthesia intraoperatively, epidural catheter placement is confirmed. However, when epidural catheters are placed intraoperatively only to provide postoperative opioid analgesia, correct catheter placement may not be confirmed by administration of a local anesthetic. The current study tests the hypothesis that the extent of sensory blockade produced by a 10-ml dose of 1.5% lidocaine can be used to predict the adequacy of epidural opioid analgesia.

Methods
Forty-nine patients undergoing major abdominal surgery in whom a lumbar epidural catheter was placed intraoperatively were studied, but no more than 3 ml 1% lidocaine had been injected. Placement of the epidural catheter was assessed in the postanesthesia care unit by administration of a 10-ml dose of 1.5% lidocaine. The extent of sensory blockade was determined using the pinprick technique: All dermatomes, T2 and below, were assessed and scored using 1 point per dermatome per side from L1 to T2 to a maximum of 24 points. Scores were arbitrarily divided into three groups, where group 1, 0-7 points; group 2, 8-15 points; and group 3, 16-24 points. Epidural morphine infusion was initiated independently of the extent of the sensory blockade and adjusted using predetermined guidelines. Adequacy of opioid-induced analgesia was determined using the visual analog scale.

Results
Significantly lower visual analog scale scores for pain at rest and with movement from epidural morphine infusion were associated with sensory blockade score of 16-24 points. Seven patients failed to obtain a detectable sensory block. No patient requested alternative analgesia. None of the epidural catheters was removed because of inadequate pain relief, even in patients who failed to obtain a detectable sensory block.

Conclusions
Extensive sensory block from 10 ml 1.5% lidocaine was associated with excellent epidural opioid analgesia. Extent of analgesia after a 10-ml test dose of 1.5% lidocaine can be used to predict the adequacy of analgesia resulting from an epidural opioid infusion. The failure of a local anesthetic dose to produce sensory blockade does not necessarily predict a failure to produce analgesia from an epidural opioid infusion, as indicated by the presence of analgesia in several patients without detectable sensory block.
Automated Echocardiographic Analysis
Authors: Perrino Albert C. Jr. MD , Luther Martha A. , O'Connor Theresa Z. , Cohen Ira S. 
Published: November 2003

Background
Although transesophageal echocardiography allows continuous intraoperative cardiac monitoring, the technique has been limited by the lack of a method for realtime, quantitative assessment of cardiac chamber size and systolic function. Automated border detection (ABD), based on an analysis of integrated backscatter, is a new technique that is purported to provide real-time, quantitative assessment of left ventricular (LV) areas and fractional area change (FAC). A prospective investigation was designed to assess the accuracy and trending capability of ABD during continuous intraoperative monitoring.

Methods
In 16 patients monitored throughout noncardiac surgical procedures, serial real-time estimates of LV end-diastolic area (EDA), end-systolic area (ESA), and FAC by ABD were compared with paired off-line manual measurements made by two experiences echocardiographers.

Results
There was a high correlation between real-time ABD estimates of LV ESA (r = 0.93), EDA (r = 0.89), and FAC (r = 0.90) to those of the off-line technique. The automated technique systematically underestimated both EDA and ESA, resulting in a small underestimation of FAC. The automated technique demonstrated an accuracy rate of 96% in tracking serial changes in LV area. The technique performed with an 83% sensitivity and 85% specificity for detecting acute changes in LV area.

Conclusions
This analysis of serial intraoperative echocardiograms demonstrates the accuracy of ABD to estimate LV area in real time and to track serial changes in cardiac area during surgery. Although ABD is an automated technique, application by personnel experienced in its operation and an echocardiographic system that includes lateral-gain adjustment controls are recommended for its optimal performance.