The contribution of d-tubocurarine-sensitive and apamin-sensitive K-channels to EDHF-mediated relaxation of mesenteric arteries from eNOS-/- mice.

The nature of the potassium channels involved in determining endothelium-derived hyperpolarizing factor-mediated relaxation was investigated in first-order small mesenteric arteries from male endothelial nitric oxide synthase (eNOS-/-)-knockout and control (+/+) mice. Acetylcholine-induced endothelium-dependent relaxation of small mesenteric arteries of eNOS-/- was resistant to N-nitro-L-arginine and indomethacin and the guanylyl cyclase inhibitor, 1H-(1,2,4) oxadiazolo (4,3-a) quinoxalin-1-one. Apamin and the combination of apamin and iberiotoxin or apamin and charybdotoxin induced a transient endothelium-dependent contraction of small mesenteric arteries from both eNOS-/- and +/+ mice. Acetylcholine-induced relaxation in eNOS-/- mice was unaffected by charybdotoxin or apamin alone but significantly inhibited by the combination of these agents. However, the combination of scyllatoxin and iberiotoxin did not mimic the inhibitory effect of the apamin/charybdotoxin combination. Tubocurarine alone completely blocked acetylcholine-induced relaxation in eNOS-/- mice. Single channel analysis of myocytes from small mesenteric arterioles revealed a large conductance calcium-activated potassium channel that was sensitive to iberiotoxin, charybdotoxin, and tetraethylammonium. Tubocurarine blocked this channel from the cytosolic side but not when applied extracellularly. Solutions of nitric oxide (NO) gas also relaxed small mesenteric arteries that had been contracted with cirazoline in a concentration-dependent manner, and the sensitivity to NO was reduced by iberiotoxin and the combination of apamin, scyllatoxin, or tubocurarine with charybdotoxin but not by apamin, charybdotoxin, scyllatoxin, or tubocurarine alone. These data indicate that acetylcholine-induced endothelium-derived hyperpolarizing factor-mediated relaxation in small mesenteric arteries from eNOS-/- involved the activation of tubocurarine and apamin-/charybdotoxin-sensitive K-channels. In eNOS+/+ mice, the acetylcholine-induced response was primarily mediated by NO and was sensitive to iberiotoxin and the combination of apamin and charybdotoxin.

[Muscle relaxants]. / Muskelrelakserende midler.

BACKGROUND: Muscle relaxants were introduced into clinical anaesthesia for the first time in 1942. The purpose of this article is to provide an overview of the history of muscle relaxants, their mode of action and their role in current anaesthetic practice. MATERIAL AND METHOD: The review is based on clinical experience, own research and a non-systematic literature search using PubMed. RESULTS: A muscle relaxant is either suxamethonium (curacit) or one of many curare compounds. One of the curare drugs was brought to Europe from South America in the 1700 s and the active substance (called d-tubocurarine) was isolated in 1935. This type of drug paralyses striated muscles that are under voluntary control by interfering with the normal signalling system between nerve and muscle. Muscle relaxants provide optimal relaxation of skeletal muscles during surgical procedures, an effect that otherwise may require the use of high doses of anaesthetic drugs. However, muscle relaxants are not anaesthetic drugs, do not affect consciousness and have no pain relieving effect. A muscle relaxant that works optimally in all clinical settings has unfortunately not been developed so far. INTERPRETATION: Muscle relaxants are generally safe drugs when used appropriately, but especially suxamethonium may have serious side effects. A muscle relaxant is regularly used during induction of anaesthesia, but less during surgery, because modern anaesthetics possess some muscle relaxing effect.

Precurarización con rocuronio y d-tubocurarina: otra perspectiva / Precurarization with rocuronium and d-tubocurarine

Objetivo: Estudiar la precurarización de la succinilcolina utilizando d-tubocurarina y rocuronio introduciendo los métodos restrictivo, conceptos de velocidad de acción y recuperación y una nueva semiología para evaluar las fasciculaciones. Material y método: Se administraron succinilcolina (1 mg x Kg-1) (n =21) sola o precedida por rocuronio o d-tubocurarina (60 ó 50 ug x Kg-1) (n =21 c/u), determinándose: la fase inicial de comienzo hasta 80 por ciento de bloqueo, tiempo de comienzo, máximo efecto, duración clínica, tiempo de reversión espontánea entre 10 por ciento y 25 por ciento y 25 por ciento a 50 por ciento. Se calculó la velocidad de acción (inicial, final y global) como la relación tiempo/bloqueo fraccionado y la velocidad de recuperación. El método restrictivo fue empleado para el estudio del tiempo de comienzo, utilizando un rango restringido de bloqueo. Las fasciculaciones fueron evaluadas por su intensidad en seis regiones anatómicas por cuatro observadores imparciales e independientes y las medias de sus valoraciones utilizadas para analizarlas. Resultados: Aparentemente ambos desfasciculantes prolongan la fase inicial, tiempo de comienzo y velocidad de la succinilcolina, pero el método restrictivo únicamente lo confirmó para el tiempo de comienzo y la velocidad global. La velocidad inicial fue más rápida que la final. El rocuronio redujo el efecto y la duración clínica e incrementó la velocidad de recuperación de la succinilcolina. Las fasciculaciones fueron más frecuentes e intensas en el tronco y miembro superior izquierdo, pero los precurarizantes las redujeron tanto en intensidad como localización Discusión: La precurarización no modifica la fase inicial de comienzo, surgiendo la posibilidad de practicar una intubación temprana. Debido al acortamiento que provoca la precurarización con rocuronio se hace evidente la necesidad precoz de nuevas dosis de relajantes.

Objective: To study the precurarization of succinylcholine with d-tubocurarine and rocuronium, using the restrictive method, speed of action and recovery principles and a particular evaluation for fasciculations Material & Methods: Patients received succinylcholine (1 mg x Kg-1) (n =21) either alone or preceded by d-tubocurarine or rocuronium (60 ó 50 micron g x Kg-1) (n =21 e/a), and the following clinical measurements were made: earlyphase of onset time (up to 80 percent blockade), onset time, maximal block, clinical duration and recovery time between 10 percent and 25 percent and 25 percent to 50 percent. Speed of action (initial, final and global)as the ratio between time and fractional blockade and speed of recovery, were calculated. Restrictive method was used for the study of the entire onset time on patients included in a limited range of final block. Intensity of fasciculations was evaluated by four independent observers blind to the drugs used in six anatomical regions and their mean values used for analysis. Results: Apparently, precurarizing drugs prolonged initial phase, onset time and reduced speed for succinylcholine, but only onset time and global speed were confirmed by restrictive method. After rocuronium, maximal effect as well as clinical duration of succinylcholine werereduced and speed of recovery increased. Fasciculations were more frequent and intense at the trunk and left upper arm, but precurarization reduced both intensity and localization prevalence. Discussion: As lack of changes on the initial phase of onset time for succinylcholine inducedby precurarization was noticed, an early tracheal intubation could be contemplated. Due to reduction on clinical duration after rocuronium,new doses of muscle relaxants are sooner necessary. The present method for evaluation of fasciculations shows how far they are spread and how effective precurarization was, given rise to doubts on previous results.

[Neuromuscular monitoring: methods and machines]. / Uberwachung der neuromuskulären Blockade - Methoden und Geräte.

Muscle relaxing agents are clinically in use for general anaesthesia to optimize the conditions to the endotracheal intubation as well as the surgical conditions. Therefore different musclerelaxants with specific pharmacological characteristics are available. Many factors that depend on the condition of the patient and the used musclerelaxant agent influence the duration of the neuromuscular blockade. Rapid reversal of their effects, particularly in cases of profound blockades, proved to be difficult. In cases of postoperative residual paralysis hypoxic complications because of failure of the ventilation increase the morbidity and mortality of the perioperative period. To avoid these complications in cause of postoperative residual neuromuscular blockade it seems to be necessary to evaluate the status of the muscle function. For the tactile or visual assessment or the objective measurement of stimulation the train-of-four (TOF), double-burst (DBS) or tetanus-stimulation of peripheral nerves like the ulnar nerve may be used. Established methods for the objective monitoring of neuromuscular function is the mechanomyography (MMG), the acceleromyography (AMG), the electromyography (EMG), the kinemyography (KMG) and the phonomyography (PMG). A sufficient recovery of the neuromuscular transmission is reached to a TOF-ratio of 0,9 and should be aimed before the extubation at the end of surgery. No subjective evaluation of the neuromuscular recovery is able to identify residual paralysis above a TOF-ratio of 0,5. Recent studies suggest that objective methods should be used to monitor neuromuscular function to avoid postoperative residual blockades.

Effects of neuromuscular blocking agents on central respiratory chemosensitivity in newborn rats

Neuromuscular blocking agents suppress central respiratory activity through their inhibitory effects on preinspiratory neurons and the synaptic drive from preinspiratory neurons to inspiratory neurons. Central CO2-chemosensitive areas, which partly consist of CO2-excited neurons, in the rostral ventrolateral medulla are thought to provide tonic drive to the central respiratory network and involve cholinergic mechanisms, which led us to hypothesize that neuromuscular blocking agents can inhibit CO2-excited neurons and attenuate respiratory CO2 responsiveness. To test this hypothesis, we used isolated brainstem-spinal cord preparations from newborn rats. The increase of C4 burst frequency induced by a hypercapnic superfusate, i.e. respiratory CO2 responsiveness, was suppressed by the application of neuromuscular blocking agents, either d-tubocurarine (10, 100M) or vecuronium (100M). These agents (40M) also induced hyperpolarization and decreases in firing frequency of CO2-excited neurons in the rostral ventrolateral medulla. Our results demonstrate that neuromuscular blocking agents inhibit CO2-excited tonic firing neurons and attenuate respiratory CO2 responsiveness.

A comparison of tubocurarine, rocuronium, and cisatracurium in the prevention and reduction of succinylcholine-induced muscle fasciculations.

Fasciculations are a common side effect of the use of succinylcholine for tracheal intubation. Many anesthesia care providers prefer to prevent them due to a possible association between fasciculations and increased intracranial and intraocular pressures. The purpose of this study was to compare the effectiveness of tubocurarine, rocuronium, and cisatracurium in the prevention and reduction of succinylcholine-induced muscle fasciculations. The study was a prospective, randomized, double-blind, clinical drug comparison. We randomly assigned 40 subjects to 1 of 4 pretreatment groups. Fasciculations were graded on a 4-point scale. A Kruskal-Wallis analysis of variance, used to analyze data collected from the fasciculation scale, demonstrated there was no statistically significant difference in efficacy between tubocurarine and rocuronium for defasciculation or between cisatracurium and saline for defasciculation. Significant differences were shown between the tubocurarine and cisatracurium groups and between the rocuronium and cisatracurium groups. Rocuronium is equally as efficacious as tubocurarine for defasciculation. Therefore, rocuronium is a valid alternative to tubocurarine for defasciculation. Cisatracurium is inferior to rocuronium and tubocurarine for defasciculation. Therefore, the use of cisatracurium is not recommended for defasciculation.

Is succinylcholine after pretreatment with d-tubocurarine and lidocaine contraindicated for outpatient anesthesia?

UNLABELLED: Because succinylcholine has obvious advantages for facilitating endotracheal intubation in the ambulatory setting (e.g., low cost, fast onset, and no need for reversal of neuromuscular block), it is important to determine whether this muscle relaxant is indeed associated with an increased incidence of postoperative myalgias, compared with alternative but more expensive nondepolarizing muscle relaxants. We studied 119 outpatients undergoing endoscopic nasal sinus surgery or septoplasty. The anesthetic technique consisted of propofol/lidocaine for induction, followed by isoflurane/nitrous oxide/oxygen for maintenance. Oral tracheal intubation was performed by using a fiberscope. Patients were randomly assigned to one of two muscle relaxant groups. Group 1 patients received d-tubocurarine 3 mg followed by succinylcholine 1.5 mg/kg. Group 2 patients received mivacurium 0.2 mg/kg. After recovery from anesthesia, patients were asked whether they had any muscle pain and/or stiffness. Pain was categorized by location and quantified by using a verbal scale (from 0 to 10). Analgesic usage and myalgias limiting ambulation were recorded. After discharge from the ambulatory surgery unit, patients were contacted by telephone on Postoperative Day 1. If patients complained of myalgias, they were contacted by telephone on Days 2 and 3. Only one patient (in the mivacurium-treated group) reported myalgia as a limiting factor in ambulation or resumption of normal activity. There were no differences between groups with respect to the incidence (21% in the succinylcholine-treated group and 18% in the mivacurium-treated group), location, or severity of myalgia. In conclusion, succinylcholine (preceded by pretreatment with d-tubocurarine and lidocaine) is not associated with an increased incidence of myalgias, compared with mivacurium, when used to facilitate tracheal intubation in patients undergoing ambulatory nasal surgery. IMPLICATIONS: The results of this study show that the frequency of muscle pains after surgery in outpatients is approximately 20%, regardless of whether succinylcholine (after precurarization) or mivacurium is used to assist in insertion of the breathing tube.

Neuromuscular blocking characteristics of vecuronium after tubocurarine-induced "fade". An experimental double-blind clinical study.

OBJECTIVE: The fade in train-of-four (TOF) monitoring is considered to be due to blocking of the prejunctional nicotinic acetylcholine receptors (AchRs). During onset of the neuromuscular block (NMB) tubocurarine (TC) causes more fade in the TOF responses than vecuronium (VEC). Therefore we wanted to investigate whether onset or duration of action of VEC or TC would be improved with a priming dose of an agent with different prejunctional activity. METHODS: The rates of NMB were measured following priming doses of 0.15 mg x kg(-1) of TC and 0.015 mg x kg(-1) of VEC with 6 min priming time. The individual time course of action of 0.6 mg x kg(-1) of TC (1.13 x ED 95) and 0.1-0.2 mg x kg(-1) of VEC (1.75-3.5 x ED95) were examined with a priming dose of the same agent or the other agent, by measurement of changes in the evoked compound EMG from the hypothenar muscle. RESULTS: Priming doses of TC decreased mean TOF ratio to 67% [95% confidence interval (CI) = 56-78] during priming time, which was significantly lower than after priming with VEC 87% (76-97; P < 0.001). Despite the higher TOF ratio, the priming dose of VEC accelerated the onset time of intubation dose of TC more than the priming dose of TC (P = 0.0018). Priming with TC prolonged the duration of VEC-induced NMB by 35-70 min compared with priming with VEC, which means that a small priming dose of TC changes VEC from a muscle relaxant with intermediate action to a long-acting agent. CONCLUSION: Priming with TC caused a lower TOF ratio; however, priming with TC did not accelerate the onset time of either agent as much as priming with VEC. It appears that potentiation of NMB after combination of VEC and TC is not dependent on "fade" receptors.

The pulmonary first-pass uptake of five nondepolarizing muscle relaxants in the pig.

BACKGROUND: It is not known whether the lungs influence the early pharmacokinetics of muscle relaxants and, if they do, whether differences in pulmonary uptake contribute to the differences in potency and/or onset time among muscle relaxants. Because the lungs are uniquely positioned, receive the entire cardiac output, have a large capillary surface area, and can temporarily store various basic drugs, the authors determined whether substantial pulmonary first-pass uptake of muscle relaxants occurs. METHODS: In 14 pigs, rocuronium, vecuronium, Org 9487, Org 7617, or d-tubocurarine were administered simultaneously with indocyanin green within 1 s into the right ventricle, and then arterial blood was sampled every 1.2 s (in the first min). The tibialis muscle response was registered mechanomyographically. RESULTS: The maximum block was 93% (68-100% [median and range]). Onset times ranged from 83 s (78-86 s) for rocuronium to 182 s (172-192 s) for d-tubocurarine. Fraction-versus-time outflow curves showed that the peak of muscle relaxants and indocyanin green occurred almost simultaneously. Pulmonary first-pass retention was negligible. The retention of muscle relaxants at 95% passage of indocyanin green was -9% (-31 to 18%). The difference in the mean transit time between muscle relaxant and indocyanin green was 1.0 (0.8 to 1.4), 0.2 (-0.8 to 0.3), 0.3 (0.2 to 0.4), 0.5 (0.2 to 1.3), and -2.2 s for rocuronium, vecuronium, Org 9487, Org 7617, and d-tubocurarine, respectively. CONCLUSIONS: There is no substantial pulmonary first-pass uptake of rocuronium, vecuronium, Org 9487, Org 7617, or d-tubocurarine in pigs. Therefore, differences in pulmonary first-pass uptake do not contribute to the differences in potency and/or onset time among muscle relaxants.

Rocuronium is the best non-depolarizing relaxant to prevent succinylcholine fasciculations and myalgia.

PURPOSE: To determine which non-depolarizing relaxant among d-tubocurarine, vecuronium, atracurium, mivacurium and rocuronium prevented muscular fasciculations and myalgia following succinylcholine. METHODS: In this double blind randomized study, 120 female patients scheduled for laparoscopic procedures were studied. They were divided into six groups of 20 according to the non-depolarizing pretreatment used: NaCl 0.9% (control), 0.05 mg.kg-1 d-tubocurarine, 0.01 mg.kg-1 vecuronium, 0.05 mg.kg-1 atracurium, 0.02 mg.kg-1 mivacurium and 0.06 mg.kg-1 rocuronium. Four minutes after the pretreatment, 1.5 mg.kg-1 succinylcholine was injected. Side effects of the pretreatment, the presence and magnitude of fasciculations, the ease of tracheal intubation, myalgia 1, 24 and 48 hr after surgery were observed. A Puritan Bennett Datex 221 NMT Relaxograph monitor was used to evaluate the neuromuscular block. RESULTS: Muscle fasciculations were observed in 19 of the 20 patients in the control group and in 3 of the 20 patients in the rocuronium group, the best of the pretreatments in that aspect. Four patients in the mivacurium group were unable to sustain more than four seconds head-lift after pretreatment (P < 0.05). Tracheal intubation conditions were better and the onset of block was faster and longer after succinylcholine in the control group (P < 0.05). Myalgias were present in 71% of the patients 24 hr postoperatively and the frequency was not different among the groups. CONCLUSION: Among the pretreatments tested, 0.06 mg.kg-1 rocuronium was the best to prevent muscular fasciculations following succinylcholine injection. In the population studied, pretreatment did not prevent postoperative myalgia. Succinylcholine 1.5 mg.kg-1 was more effective without a non-depolarizing pretreatment.

Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study.

The possibility of using polysorbate 80-coated polybutylcyanoacrylate nanoparticles to deliver low molecular polar hydrophilic drugs to the CNS has been studied. Tubocurarine (a quaternary ammonium salt) does not penetrate the normal intact blood-brain barrier. However, the injection of this drug directly into the cerebral ventricles of the brain provokes the development of epileptiform seizures as assessed by electroencephalogram (EEG). An in situ perfused rat brain technique was used as an experimental technique together with a simultaneous recording of the EEG. Nanoparticles were prepared by butylcyanoacrylate polymerization in an acidic medium. Fifteen minutes after the introduction of tubocurarine-loaded polysorbate 80-coated nanoparticles into the perfusate, epileptiform spikes in the EEG appeared. Intraventricular injection of tubocurarine caused the appearance of the EEG seizures 5 min after administration. Neither tubocurarine solution nor tubocurarine-loaded nanoparticles without polysorbate 80 or a mixture of polysorbate 80 and tubocurarine were able to influence the EEG. Thus only the loading of tubocurarine onto the polysorbate 80-coated nanoparticles appears to enable the transport of this quaternary ammonium compound through the blood-brain barrier.

Heart rate variability and the prone position under general versus spinal anesthesia.

STUDY OBJECTIVE: To evaluate heart rate (HR) variability in the prone position with power spectral heart rate (PSHR) analysis during spinal and general anesthesia. DESIGN: Prospective, clinical evaluation of HR variability in the prone position. SETTING: Tertiary care teaching hospital. PATIENTS: 20 healthy, ASA physical status I and II patients scheduled for elective lumbar spine surgery in the prone position. INTERVENTIONS: Anesthetic technique was either a standard general anesthetic or spinal anesthetic, based on the preference of the patient. Power spectral heart rate, HR, and blood pressure (BP) readings were determined prior to anesthetic intervention and as soon as a stable PSHR reading was available in the prone position. MEASUREMENTS AND MAIN RESULTS: Heart rate and BP were recorded at baseline prior to anesthesia and at the time of stable PSHR data in the prone position. Power spectral heart rate data included low-frequency activity (LFa), high-frequency activity (HFa), and the ratio (LFa/HFa). Spinal anesthesia level was recorded by thoracic dermatome at complete onset. Data were collected from 20 patients; 12 patients chose spinal anesthesia and 8 chose general anesthesia. The prone position resulted in significant increase in HR in the spinal group and significant decrease in BP in the general anesthesia group. Low-frequency activity and LFa/HFa ratio were unchanged in the spinal anesthesia group and were significantly decreased in the general anesthesia group. Spinal level was T8.7. CONCLUSIONS: The association of less change in LFa activity and preservation of BP on assumption of the prone position in patients during low spinal anesthesia suggests better preservation of autonomic nervous system compensatory mechanisms during low spinal anesthesia than with general anesthesia.

The impact of choice of muscle relaxant on postoperative recovery time: a retrospective study.

UNLABELLED: To test the hypothesis that the use of long-acting muscle relaxants is associated with prolonged postoperative recovery when compared with the use of shorter-acting relaxants, we undertook a retrospective study of 270 patients with induced paralysis recovering from general anesthesia. We calculated the mean recovery time associated with each muscle relaxant used. Regression analyses were performed to control for potential confounding of the results by length and type of surgery, as well as age and sex. Taking these into account, the adjusted difference in mean recovery time between patients receiving short- and intermediate-acting relaxants (mivacurium, atracurium, and vecuronium) versus those receiving long-acting relaxants (d-tubocurarine, pancuronium, and pancuronium and d-tubocurarine combination) was 30 min (95% confidence interval [CI] 8-53). The adjusted difference in mean recovery time between patients receiving vecuronium and those receiving pancuronium (i.e., the single most frequently used drug in each category) was 33 min (95% CI 1-66). Shortened recovery time accounted for an estimated average $37.95 decrease in recovery room charge per patient when vecuronium was used instead of pancuronium, versus a $22.84 increase in drug cost. Our data and analyses support the hypothesis that the use of long-acting muscle relaxants is associated with prolonged recovery after surgery and provide preliminary evidence that restricting the use of the more expensive, shorter-acting muscle relaxants may represent a false economy. IMPLICATIONS: In this retrospective study, the use of old-fashioned, inexpensive, long-acting paralyzing drugs was found to be associated with prolonged postoperative recovery. This has implications when deciding whether, as an economic measure, to restrict the use of the more expensive, shorter-acting paralyzing drugs, because prolonged recovery also has a price.

The effects of chronic tacrine therapy on d-tubocurarine blockade in the soleus and tibialis muscles of the rat.

Tacrine (THA) is an anticholinesterase drug used to manage Alzheimer's dementia, but it is not clear how its chronic use might affect response to nondepolarizing muscle relaxants. We determined the magnitude and time course of the effects of chronic oral THA and of intravenous (IV) THA on d-tubocurarine (dTC) blockade at the soleus and tibialis muscles. Six groups of adult rats were given 10 mg/kg THA twice daily by gavage for 1, 2, 4, or 8 wk (chronic THA groups), or 1 mL of saline twice daily by gavage for 1-8 wk (control), or IV THA approximately 20 min before (acute), and the cumulative dose-response curves of dTC at the tibialis and soleus muscles were determined during indirect train-of-four stimulation in the anesthetized, mechanically ventilated rat. The 50% effective dose (ED50) and 95% effective dose (ED95) of dTC in control rats were (mean +/- SD) 30 +/- 10 and 61 +/- 18 microg/kg in the tibialis and 32 +/- 8 and 75 +/- 19 microg/kg in the soleus; respectively. IV THA increased the ED95 of dTC 2.5- to 3-fold (P < 0.05) but did not alter the ED50. Chronic THA increased both the ED50 and ED95 of dTC 1.5- to 2-fold (P > or = 0.05), and this effect tended to decrease with duration of THA therapy. We conclude that chronic THA therapy in rats causes resistance to dTC, with a tendency for the resistance to decrease with time, probably because of down-regulation of postsynaptic acetylcholine receptors. The same may apply to Alzheimer's patients taking THA chronically.

Neuromuscular blocking actions of the aminoglycoside antibiotics sisomicin and micronomicin in the rabbit.

The neuromuscular blocking actions of sisomicin sulfate (SISO), micronomicin sulfate (MCR) and d-tubocurarine (dTc) were studied in 20 rabbits anesthetized with halothane. The i.v. administration of SISO 20-40 mg/kg, MCR 40-80 mg/kg or dTc 0.1-0.3 mg/kg resulted in dose-dependent decreases in twitch tension. The ED50s for SISO, MCR and dTc were 23.5, 58.2 and 0.2 mg/kg, respectively. SISO- and MCR-induced neuromuscular blockade was partially antagonized by neostigmine or by calcium.

Comparative use of muscle relaxants and their reversal in three European countries: a survey in France, Germany and Great Britain.

A survey was conducted among British, French and German anaesthetists to evaluate possible national differences in the peri-operative use of muscle relaxants and their reversal agents. The same non-depolarizing relaxants are used in all three countries, with the exception of d-tubocurarine, which is only available in Great Britain, and alcuronium which is mainly used in Germany. The French anaesthetists seem to use significantly less succinylcholine than their peers in Great Britain or Germany for both elective and emergency intubation. Monitoring of neuromuscular blockade still relies mainly on "clinical judgement'. Reversal of non-depolarizing muscle relaxants is performed routinely in Great Britain, while a substantial number of French anaesthetists avoid the use of a reversal. Dose regimes for neostigmine vary largely, with German anaesthetists administering the lowest, and British anaesthetists administering the highest doses. Side effects of reversal agents are reported by colleagues from all three countries in too high a percentage to justify uncritical administration of these drugs. In Germany there seems to be a noteworthy lack of recovery facilities.

Fear induced by the blockade of GABAA-ergic transmission in the hypothalamus of the cat: behavioral and neurochemical study.

Intrahypothalamic injections of d-Tubocurarine (DT) and bicuculline (BM) in the cat produced a fear reaction characterized by terrific mewing, increased locomotor activity, jumps and attempt to escape from the chamber, pupillary dilatation, increased respiratory rate, and sometimes urination and defecation. HPLC analysis showed a significant increase in the noradrenergic system activity in the emotional brain areas (hypothalamus, midbrain, amygdala) and frontal cortex at the time of the fear drive. No changes in the cat's behavior and in the monoaminergic systems activity occurred after muscimol+d-Tubocurarine injections into the hypothalamus. Similar behavioral and neurochemical effects evoked by DT and BM suggest that the fear response evoked by DT does not result from the blockade of N-cholinergic transmission but rather from their action on GABAA receptor complex. The results obtained indicate that the central triggering mechanism for fear drive depends on the blockade of GABAA-ergic transmission.