bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the Endocardial Endothelium in the Negative Inotropic Effects of Thiopental
Authors: Bettens Karin M. , De Hert Stefan G. , Sys Stanislas U. , Brutsaert Dirk L. 
Published: November 2003

Background
Myocardial function is regulated by endocardial endothelium (EE). Several studies have demonstrated the involvement of vascular endothelium in regulating the vasoactive effects of anesthetic agents. Because vascular endothelium and EE form a contiguous layer, it was postulated that EE might also be involved in regulating the inotropic effects of anesthetics. The effects of thiopental on isolated feline papillary muscle with and without EE were examined.

Methods
The study was performed on isolated cat papillary muscles (n = 48). The effects of increasing doses of thiopental (1.5, 3, 6, 9, 12, and 24 micrograms/ml) on isometric and isotonic muscle contraction parameters were evaluated in three protocols under different experimental conditions. In the first protocol, the effects of thiopental were studied in the muscles with an intact EE (group A, n = 8) and muscles in which the EE was selectively damaged by a 1-s immersion in 0.5% Triton X-100 (group B, n = 8). In the second protocol, cumulative concentration responses for thiopental were obtained in muscles with (group C, n = 8) and without (group D, n = 8) EE, pretreated with 10(-3) M of the blocking NG-nitro-L-arginine methyl ester (L-NAME). In the third protocol, the same cumulative concentration responses were obtained for thiopental in muscles with (group E, n = 8) and without (group F, n = 8) EE after pretreatment with 5 x 10(-4) M L-arginine.

Results
In the presence of an intact EE, thiopental induced a dose-dependent decrease in myocardial function. With the EE removed, low doses of thiopental (1.5 to 6 micrograms/ml) no longer altered myocardial function. Pretreatment of the muscles with L-NAME inhibited the negative inotropic effects of low doses of thiopental and mimicked the response obtained after EE was removed. Pretreatment with L-arginine slightly accentuated the negative inotropic effects of low doses of thiopental.

Conclusions
The negative inotropic actions of small doses of thiopental depend on the presence of an intact EE. Pretreatment of the muscles with L-NAME inhibited the negative inotropic effects of low doses of thiopental, suggesting possible involvement of the nitric oxide pathway.
Nitrict Oxide Synthase Inhibitors, 7-Nitro Indazole and Nitro sup G -L-Arginine Methyl Ester, Dose Dependently Reduce the Threshold for Isoflurane Anesthesia
Authors: Pajewski Thomas N. , DiFazio Cosmo A. , Moscicki Jeffrey C. , Johns Roger A. 
Published: November 2003

Background
Nitric oxide (NO), a recognized cell messenger for activating soluble guanylate cyclase, is produced by the enzyme NO synthase in a wide variety of tissues, including vascular endothelium and the central nervous system. The authors previously reported the possible involvement of the NO pathway in the anesthetic state by showing that a specific NO synthase inhibitor, nitroG-L-arginine methyl ester (L-NAME), dose dependently and reversibly decreases the minimum alveolar concentration (MAC) for halothane anesthesia. The availability of a structurally distinct inhibitor selective for the neuronal isoform of NO synthase, 7-nitro indazole (7-NI), allowed for the possibility of dissociating the central nervous system effects of neuronal NO synthase inhibition from the cardiovascular effects of endothelial NO synthase inhibition.

Methods
The effect of two structurally distinct inhibitors of NO synthase, L-NAME and 7-NI, on the MAC of isoflurane was investigated in Sprague-Dawley rats while concurrently monitoring the animals' arterial blood pressure and heart rate. L-NAME (1 to 30 mg/kg given intravenously, dissolved in 0.9% saline) and 7-NI (20 to 1,000 mg/kg given intraperitoneally, dissolved in arachis oil) were administered after determining control MAC and 30 min before determining MAC in the presence of NO synthase inhibitor.

Results
L-NAME and 7-NI caused a dose-dependent decrease from isoflurane control MAC (maximal effect: 35.5 +/- 2.5% and 43.0 +/- 1.7%, respectively) with a ceiling effect observed for both NO synthase inhibitors (above 10 mg/kg and 120 mg/kg, respectively). L-NAME administration significantly increased systolic and diastolic blood pressures (maximal effect: 39.9 +/- 2.2% and 64.3 +/- 4.0%, respectively), which were not accompanied by any changes in heart rate. 7-NI administration resulted in no changes in blood pressure and a small but clinically insignificant decrease in heart rate.

Conclusions
Inhibition of the NO synthase pathway decreased the MAC for isoflurane, which suggests that inhibition of the NO pathway decreases the level of consciousness and augments sedation, analgesia, and anesthesia. The MAC reduction by two structurally distinct NO synthase inhibitors supports that this is a specific effect on NO synthase. Furthermore, the action of the neuronal NO synthase inhibitor 7-NI supports an effect selective for neuronal NO synthase and also avoids the hypertensive response of generalized NO synthase inhibitors.
A Beta-adrenoceptor Agonist Evokes a Nitric Oxide-cGMP Relaxation Mechanism Modulated by Adenylyl Cyclase in Rat Aorta
Authors: Iranami Hiroshi , Hatano Yoshio , Tsukiyama Yoshi , Maeda Hiroshi , Mizumoto Kazuhiro 
Published: November 2003

Background
The objective of this study was to characterize the effects of halothane on the agonist-induced nitric oxide-cyclic GMP (NO-cGMP) mechanisms by comparing the intracellular signal transduction mediating isoproterenol- and acetylcholine-induced nitric oxide formation.

Methods
Isoproterenol-induced relaxations of rat aortic rings with and without endothelia were examined in the absence and presence of halothane. Studies were also done in the presence of inhibitors of nitric oxide-synthase, adenylyl cyclase, calmodulin, protein kinase A, and intracellular Ca2+ release mechanism. The relaxations under some of these conditions were compared with those induced by acetylcholine. Cyclic nucleotide contents of the rings were also measured.

Results
Isoproterenol relaxed aortic rings via the endothelium-dependent nitric oxide-cyclic GMP mechanism. Inhibition of adenylyl cyclase or of protein kinase A attenuated the isoproterenol-induced relaxations significantly but did not affect those induced by acetylcholine. Inhibition of intracellular Ca2+ release abolished the acetylcholine-induced relaxations but did not affect those induced by isoproterenol. Calmodulin inhibition attenuated both agonist-induced relaxations significantly. Unlike acetylcholine-induced relaxation, that induced by isoproterenol was not affected by halothane. Isoproterenol increased both the cyclic adenosine monophosphate and cGMP contents of rings significantly when endothelia were intact. Inhibition of nitric oxide synthase attenuated the isoproterenol-induced cGMP content increases significantly but did not affect the cyclic adenosine monophosphate content increases. Halothane (2%) did not affect isoproterenol-induced increases in nucleotide content.

Conclusions
Isoproterenol-induced nitric oxide formation requires the activation of constitutive nitric oxide synthase, but the Ca2+ release mechanism is not involved in activating this enzyme. Halothane can inhibit the nitric oxide-cyclic GMP mechanism only when Ca2+ release is greatly involved in the activation of constitutive nitric oxide synthase.
Sevoflurane Depresses Myocardial Contractility Less than Halothane during Induction of Anesthesia in Children
Authors: Holzman Robert S. , van der Velde Mary E. , Kaus Sarah J. , Body Simon C. , Colan Steven D. , Sullivan Lorna J. , Soriano Sulpicio G. 
Published: November 2003

Background
Cardiovascular stability is an important prerequisite for any new volatile anesthetic. We compared echocardiographically derived indices of myocardial contractility during inhalation induction with sevoflurane and halothane in children.

Methods
Twenty children were randomized to receive either halothane or sevoflurane for inhalation induction of anesthesia. No preoperative medications were given. Myocardial contractility was evaluated at baseline and at sevoflurane and halothane end-tidal concentrations of 1.0 minimum alveolar concentration (MAC) and 1.5 MAC.

Results
There were no differences between groups in patient age, sex, physical status, weight, or height. Equilibration times and MAC multiples of sevoflurane and halothane were comparable. Vital signs remained stable throughout the study. Left ventricular end-systolic meridional wall stress increased with halothane but remained unchanged with sevoflurane. Systemic vascular resistance decreased from baseline to 1 MAC and 1.5 MAC with sevoflurane. Halothane depressed contractility as assessed by the stress-velocity index and stress-shortening index, whereas contractility remained within normal limits with sevoflurane. Total minute stress and normalized total mechanical energy expenditure, measures of myocardial oxygen consumption, did not change with either agent.

Conclusions
Myocardial contractility was decreased less during inhalation induction of anesthesia with sevoflurane compared with halothane in children. Although the induction of anesthesia with sevoflurane or halothane was equally well tolerated, the preservation of myocardial contractility with sevoflurane makes it an attractive alternative for inducing anesthesia in children.
N-Butyl Tetracaine as a Neurolytic Agent for Ultralong Sciatic Nerve Block
Authors: Wang G. K. , Vladimirov M. , Quan C. , Mok W. M. , Thalhammer J. G. , Anthony D. C. 
Published: November 2003

Background
Neurolytic agents such as phenol (5% to 10%) and absolute alcohol have long been used clinically to destroy the pathogenic nerve regions that manifest pain. Both phenol and alcohol are highly destructive to nerve fibers. However, these agents exert only weak local anesthetic effects and therefore are difficult to administer to alert patients without pain. This report describes a tetracaine derivative that displays both local anesthetic and neurolytic properties. Studies with such a compound may lead to the design of neurolytic agents that are more effective and more easily administered than phenol and alcohol.

Methods
A tetracaine derivative, N-butyl tetracaine quaternary ammonium bromide, was synthesized, and its ability to elicit sciatic nerve block of sensory and motor functions in vivo was tested in rats. A single dose of 0.1 ml N-butyl tetracaine at 37 mM was injected into the sciatic notch. Transverse sections of treated sciatic nerves were subsequently examined to determine the neurolytic effect of this drug. Finally, the local anesthetic properties of N-butyl tetracaine were studied in vitro; both tonic inhibition and use-dependent inhibition of Na+ currents in neuronal GH3 cells were characterized under whole-cell voltage-clamp conditions.

Results
N-butyl tetracaine at 37 mM (equivalent to 1.11% tetracaine-hydrochloric acid concentration) elicited prolonged sciatic nerve block of the withdrawal response to noxious pinch in rats for more than 2 weeks. The withdrawal response was fully restored after 9 weeks. Parallel to sensory block, motor functions of the hind legs were similarly blocked by this drug. Morphologic examinations 3 and 5 weeks after a single injection of drug revealed degeneration of many sciatic nerve fibers, consistent with the results of functional tests. Finally, N-butyl tetracaine was found to be a potent Na+ channel blocker in vitro. It produced strong tonic and use-dependent inhibition of Na+ currents with a potency comparable to that of tetracaine.

Conclusions
A single injection of N-butyl tetracaine produces ultralong sciatic nerve block in rats. This compound possesses both local anesthetic and neurolytic properties and may prove useful as a neurolytic agent in pain management.
Sympathetic and Mesenteric Venous Responses to Baroreceptor or Chemoreceptor Stimulation during Epidural Anesthesia in Rabbits
Authors: Hogan Quinn H. , Kulier Alexander , Bosnjak Zeljko J. , Kampine John P. 
Published: November 2003

Background
Baroreceptor and chemoreceptor reflexes maintain homeostasis through mechanisms that involve sympathetic activation. Because sympathetic control of the mesenteric veins plays a central role in hemodynamic responses to stress, the effects of epidural blockade on reflex responses to hypoxia and bilateral carotid occlusion (BCO) were examined by monitoring direct measures of splanchnic sympathetic neural traffic and mesenteric venous capacitance.

Methods
Rabbits were studied during alpha-chloralose anesthesia and mechanical ventilation. Sympathetic efferent nerve activity to the mesenteric vessels was measured by surgically placed electrodes, and mesenteric venous diameter was measured by videomicroscopy. Heart rate and mean arterial pressure were monitored by intraarterial cannulation. Intraluminal venous pressure was monitored by a servo-null micropressure technique. Responses were recorded during repeated administration of three different stresses, F1O2 = 0% for 40 s, F1O2 = 11% for 2.5 min, and BCO for 60 s. Animals received either thoracolumbar epidural blockade (0.4 ml/kg lidocaine 1.5%; n = 7) or 15 mg/kg intramuscular lidocaine (n = 7).

Results
Hypoxia and BCO produced sympathetic stimulation and active constriction of mesenteric veins. Epidural anesthesia accentuated the mean arterial pressure decrease from F1O2 of 0%, caused the 11% response to F1O2 to become depressor instead of pressor, and decreased the pressor effect BCO. Sympathetic efferent nerve activity and venous diameter responses to hypoxia and BCO were attenuated or eliminated.

Conclusions
The hemodynamic effects of hypoxia result from a combination of direct depression and reflex activation. Thoracolumbar epidural anesthesia in rabbits impairs compensatory reflexes invoked by chemoreceptor stimulation and eliminates response to baroreceptor stimulation. Loss of splanchnic control of mesenteric capacitance contributes to the inhibition of the hemodynamic response to hypoxia or BCO during epidural anesthesia in rabbits.
Effects of Pre- and Postischemic Administration of Thiopental on Transmitter Amino Acid Release and Histologic Outcome in Gerbils
Authors: Amakawa Kazuhiko , Adachi Naoto , Liu Keyue , Ikemune Keizo , Fujitani Taro , Arai Tatsuru 
Published: November 2003

Background
The mechanism by which barbiturates protect neurons against ischemia is unclear, particularly when they are given after ischemia or reperfusion begins. Because an excess release of excitatory neurotransmitters causes postsynaptic membrane depolarization, which triggers neuronal damage in ischemia, the effects of thiopental on histologic outcome, ischemia-induced amino acid release, and anoxic depolarization in gerbils were studied.

Methods
The effects of different doses of thiopental administered before or after ischemia were examined morphologically by assessing delayed neuronal death in hippocampal CA1 pyramidal cells produced by forebrain ischemia for 3 min in gerbils. The ischemia-induced changes in output of aspartate, glutamate, glycine, taurine, and gamma-aminobutyric acid were measured using a microdialysis-high-performance liquid chromatography procedure, and the differences among a halothane-anesthetized group, a thiopental-administered group, and a group given thiopental after a period of ischemia were evaluated. The changes induced in the direct-current potential in the hippocampal CA1 area by forebrain ischemia were compared in animals anesthetized with halothane and those given thiopental.

Results
Preischemic administration of thiopental at all doses decreased the risks for delayed neuronal death (P < 0.01). Post-ischemic administration at a dosage of 2 mg.kg-1.min-1 for 60 min protected neurons, but the same dose for 10 min did not ameliorate the cell injury. Forebrain ischemia produced marked increases in all amino acids 3 to 6 min after the start of recirculation in the halothane-anesthetized gerbils, whereas thiopental anesthesia (2 mg.kg-1.min-1) reduced these increases throughout the experimental period, except for glycine (P < 0.01). The initiation of thiopental after reflow did not markedly diminish these increases. Thiopental anesthesia prolonged the onset of anoxic depolarization and reduced its maximal amplitude.

Conclusions
Thiopental helps protect the brain from ischemia, although treatment with this agent after ischemia requires a larger dose than that before ischemia. The effect of preischemic treatment may be related to the suppression of the excitatory amino acid release and the direct-current potential shift.
Cysteine Conjugate β-Lyase-dependent Biotransformation of the Cysteine S-Conjugates of the Sevoflurane Degradation Product Compound A in Human, Nonhuman Primate, and Rat Kidney Cytosol and Mitochondria
Authors: Iyer Ramaswamy A. , Anders M. W. 
Published: November 2003

Background
2-(Fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (compound A) is a fluorinated alkene formed by the degradation of sevoflurane in the anesthesia circuit. Compound A is toxic to the kidneys in rats and undergoes glutathione-dependent metabolism in vivo. Several nephrotoxic halogenated alkenes also undergo cysteine conjugate beta-lyase-dependent biotransformation. These experiments were designed to test the hypothesis that cysteine S-conjugates of compound A undergo beta-lyase-dependent biotransformation.

Methods
S-[2-(Fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine 4, S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-L-cysteine 5, and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine 11 were incubated with rat, human, and nonhuman primate (cynomolgus, rhesus, and marmoset) kidney cytosol and mitochondria. beta-Lyase activity was determined by measuring pyruvate formation.

Results
Compound A-derived conjugates 4 and 5 as well as conjugate 11, a positive control, were substrates for cytosolic and mitochondrial beta-lyase from human, nonhuman primate, and rat kidney. For all substrates, beta-lyase activity was highest in the rat and lowest in the human and was higher in cytosol than in mitochondria. Conjugate 11 was a much better substrate than conjugates 4 or 5. The biotransformation of conjugates 4, 5, and 11 was inhibited by the beta-lyase inhibitor (aminooxy)acetic acid and was stimulated by the amino group acceptor 2-keto-4-methylthiolbutyric acid, indicating a role for beta-lyase.

Conclusions
These data confirm the presence of beta-lyase activity in human and rat kidney and show that activity is also present in kidney tissue from nonhuman primates. The data also show that compound A-derived conjugates 4 and 5 undergo beta-lyase-catalyzed biotransformation. beta-Lyase activity in rat and nonhuman primate kidney tissue was 8 to 30 times and one- to three times, respectively, higher than in human kidney tissue.
Local Anesthetic Administration for Awake Direct Laryngoscopy
Authors: Sitzman Todd B. , Rich George F. , Rockwell Jeffrey J. , Leisure George S. , Durieux Marcel E. , DiFazio Cosmo A. 
Published: November 2003

Background
Glossopharyngeal nerve (GPN) blocks may provide reliable analgesia for awake direct laryngoscopy, although this has not been evaluated prospectively. This study was designed to determine if GPN blocks provide a superior route of local anesthetic administration for awake direct laryngoscopy as measured by hemodynamic, gag, and subjective pain responses.

Methods
A prospective, randomized, single-blinded, crossover design was used. All participants (n = 11) were anesthesiologists. Three routes of local anesthetic administration were evaluated: 2 min of 2% viscous lidocaine swish and gargle (S&G); S&G combined with 10% lidocaine spray (S&G/spray); and S&G combined with 1% lidocaine bilateral GPN blocks (S&G/block; anterior tonsillar pillar method). Five minutes after the local anesthetic was administered, laryngoscopy was performed and sustained for 20 s. Noninvasive hemodynamic measurements and serum lidocaine concentrations were determined. Visual analogue scale scores and a poststudy questionnaire were used to assess participants' ability to tolerate local anesthetic administration and laryngoscopy and their choice for use in clinical practice.

Results
No significant hemodynamic changes were observed, although there was a modest increase (< 15%) in heart rate in the S&G/block group in the first minute after laryngoscopy. Serum lidocaine concentrations were higher (P < 0.05) in the S&G/block group at 5 and 10 min (0.5 +/- 0.1 and 1.0 +/- 0.2 microgram/ml) compared with the S&G group. Participants' visual analogue scale scores, which assessed their ability to tolerate laryngoscopy, showed that S&G (5.4 +/- 0.9) resulted in more discomfort (P < 0.05) than either S&G/spray (3.5 +/- 0.9) or S&G/block (3.3 +/- 0.7). The laryngoscopist's visual analogue scale scores, which assessed the ease of visualization, revealed a trend (P < 0.08) toward less coughing and gagging with S&G/spray (1.8 +/- 0.9) compared with S&G (4.0 +/- 1.3) and S&G/block (3.7 +/- 1.1). Oropharyngeal discomfort lasting 24 h or more was reported by 91% of participants after S&G/block, whereas no participant reported oropharyngeal discomfort after S&G or S&G/spray. Significantly more participants (73%) indicated their preference for using S&G/spray in future clinical practice compared with S&G (P < 0.01) and S&G/block (P < 0.05).

Conclusions
Glossopharyngeal nerve blocks do not provide a superior route of local anesthetic administration for awake direct laryngoscopy. Two minutes of 2% viscous lidocaine S&G followed by 10% lidocaine spray was the anesthetic route preferred by participants and laryngoscopists.
Isoflurane and Sevoflurane Interact with the Nicotinic Acetylcholine Receptor Channels in Micromolar Cconcentrations
Authors: Scheller Michaela , Bufler Johannes , Schneck Hajo , Kochs Eberhard , Franke Christian 
Published: November 2003

Background
This study was performed to elucidate and compare the effects of sevoflurane and of isoflurane on the nicotinic acetylcholine receptor of mouse myotubes. The experiments were done with special reference to anesthetic concentrations considerably less than those used for clinical anesthesia.

Methods
The patch-clamp technique was used to record acetylcholine-activated currents from the embryonic type of the nicotinic acetylcholine receptor in the outside-out mode. A piezo-driven liquid filament switch was used for the ultrafast application of acetylcholine alone or in combination with isoflurane or sevoflurane. In addition, the patches were preexposed to either anesthetic, preceding the activation with acetylcholine.

Results
The current elicited by acetylcholine was reduced reversibly and in a concentration-dependent manner by both anesthetics, which were equally effective. Preexposure of the patches to isoflurane or sevoflurane showed an additional inhibition that was present at micromolar concentrations. The time courses of current decay could be fitted by single exponentials for isoflurane. At higher concentrations of sevoflurane, the current decay became biexponential. In contrast to isoflurane, sevoflurane increased the time constants of desensitization when applied in low concentrations.

Conclusions
At the nicotinic acetylcholine receptor, isoflurane and sevoflurane act primarily through the same mechanisms: Both affect the open and the closed state of the channels in concentrations equal to and less than those encountered clinically. The kinetics of desensitization, however, are altered in a different manner. Thus there may be several different sites of interaction.