Monitoring orbicularis oculi predicts good intubating conditions after vecuronium in children

PURPOSE: The aim of the study was to compare visual estimation of onset of neuromuscular blockade at both the adductor pollicis (AP) and the orbicularis oculi (OO) in children and to determine if monitoring the OO could predict good intubating conditions during vecuronium-induced neuromuscular blockade. METHODS: Thirty ASAI--II children (1.5-9 yr) were studied. Anaesthesia was induced with 6-8 mg.kg-1 thiopentone. The ulnar nerve at the wrist and the temporal branch of the facial nerve were stimulated every 10 sec using train-of-four (TOF) stimuli. Vecuronium, 0.15 mg.kg-1, was administered as a bolus. The responses at both the OO and the AP were evaluated visually. Patients were randomly divided into two groups. In the AP group (n = 15), the trachea was intubated when the AP was completely blocked. In the OO group (n = 15), intubation was performed when the OO was completely blocked. Intubating conditions were scored on a scale of 1 to 4. RESULTS: All the patients had complete blockade at both the orbicularis oculi and the adductor pollicis. In the two group, time from injection of vecuronium to complete neuromuscular blockade was shorter at the orbicularis oculi than at the adductor pollicis, 1.5 +/- 0.5 min vs 2.3 +/- 0.7 min, respectively, (P < 0.05; mean +/- SD) in the AP group, 1.7 +/- 0.3 min vs 2.3 +/- 0.8 min, respectively in the OO group (P < 0.05). Intubating conditions were excellent in all patient except one, where it was rated as good. They did not differ between groups. CONCLUSION: Following administration of 0.15 mg.kg-1 vecuronium in children, monitoring of the OO can detect good intubating conditions 0.7 min earlier than with monitoring of the AP.     

Potential of succinylcholine-induced neuromuscular blockade by nitrous oxide

To evaluate the potentiating effect of nitrous oxide on the succinylcholine (SCh)-induced neuromuscular blockade, 0.16, 0.20, 0.25 or 0.31 mg.kg-1 of Sch was given during thiamylal-fentanyl anesthesia with or without nitrous oxide, and the evoked electromyograph of hypothenar muscles was measured. ED50 and ED95 in the group receiving nitrous oxide were 0.187 and 0.301 mg.kg-1, and 0.218 and 0.389 mg.kg-1 in the group not receiving nitrous oxide respectively. In the presence of nitrous oxide, the dose-response curve (DRC) was shifted to the left significantly (P < 0.01). By the multiple regression analysis, the degree of the neuromuscular blockade was shown to be affected by dose and nitrous oxide. It was demonstrated that nitrous oxide decreased electromyographically measured SCh requirements by 16.1%. In addition, the dose-effect relationship for SCh-induced neuromuscular blockade varied widely, and gender did not affect the degree of block.     

Evidence for regulation of the NADH peroxidase gene (npr) from Enterococcus faecalis by OxyR

To evaluate residual effects of inhalational anesthetics after reversal of neuromuscular blocking agent, neuromuscular function was monitored after halothane or sevoflurane anesthesia in thirty-seven patients (ASA physical status I or II) for elective surgery after obtaining informed consent. Electromyograph of the adductor pollicis muscle in response to train of four (TOF) stimulation was monitored throughout the study. The first twitch of TOF (T1; % of its control) and the ratio of the fourth twitch to the first twitch of TOF (T4/T1; TR) were recorded at 0, 2, 5, 10, and 15 min after reversal. The patients were divided into five groups; 1) the fentanyl group (n = 7) received fentanyl/N2O; 2) in the halothane stop group (n = 6), halothane was discontinued at least fifteen minutes before neostigmine administration; 3) in the halothane stable group (n = 7), 0.7% halothane was maintained until fifteen minutes after neostigmine; 4) in the sevoflurane stop group (n = 12), sevoflurane was discontinued fifteen minutes before the reversal; 5) in the sevoflurane stable group (n = 5), 3% sevoflurane was maintained until fifteen minutes after the reversal. Anesthesia was induced by thiopental 4 mg.kg-1 and suxamethonium 1 mg.kg-1 and the patients were intubated. After initial dose of vecuronium 0.1 mg.kg-1, the additional dose of 0.02 mg.kg-1 was administered to maintain T1 under 10% of the control value. At the end of the surgery atropine 0.015 mg.kg-1 and neostigmine 0.04 mg.kg-1 were administered to reverse vecuronium when T1 had recovered to 25% of its control. Halothane groups did not differ from fentanyl group. Recovery of T1 at 15 min was suppressed after discontinuation of sevoflurane (86.0 +/- 8.2%) in comparison with fentanyl (97.0 +/- 8.3%). Both T1 (75.4 +/- 12.2%) and TR (68.0 +/- 12.6%) at 15 min after the reversal during 3% sevoflurane inhalation were below those of the stable group. We conclude that the residual sevofulrane after discontinuation of inhalation may impair the neuromuscular transmission after the reversal of neuromuscular blockade. Neuromuscular function should be monitored after the end of anesthesia even though the patient is fully awake.     

Neuromuscular blockade with vecuronium and its reversal with edrophonium during total intravenous anesthesia, neuroleptanalgesia and sevoflurane anesthesia

The neuromuscular blocking effect of vecuronium and its reversibility ith edrophonium were studied under total intravenous anesthesia (TIVA) and compared with those under NLA or sevoflurane anesthesia (SA) in 30 surgical patients. The degree of neuromuscular blockade was evaluated by acceleration of thumb adduction in response to supramaximal stimulation of the ulnar nerve using Accelograph (Biometer). TIVA was induced with droperidol 0.25 mg.kg-1, fentanyl 2-4 micrograms.kg-1 and ketamine 2 mg.kg-1, and maintained with continuous infusion of ketamine 2 mg.kg-1.h-1 with 30-35% O2 in air. NLA was induced with droperidol 0.25 mg.kg-1 and fentanyl 5-10 micrograms.kg-1 and maintained with 66% nitrous oxide in oxygen. SA was induced with thiamylal 5 mg.kg-1 i.v. and maintained with 66% nitrous oxide in oxygen supplemented with sevoflurane (1 MAC). A single bolus intravenous injection of vecuronium 0.1 mg.kg-1 was used for paralysis and reversed with edrophonium 0.75 mg.kg-1 followed by atropine 0.015 mg.kg-1 when the TOF ratio returned to 25%. The times required from administration of vecuronium to completion of maximal block with TIVA, NLA and SA were 196.5 +/- 52.2 sec, 182.5 +/- 47.6 sec and 166.0 +/- 69.0 sec, respectively. There was no significant difference among them. The times from completion of maximal block to 25% recovery of the twitch height in TIVA and NLA were 39.5 +/- 11.0 min and 37.4 +/- 5.8 min without significant difference. Those values, however, were significantly shorter than 64.5 +/- 35.2 min of SA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cisatracurium

Cisatracurium is one of ten isomers that form the racemic mix of atracurium (51W89 or 1 R-cis, 1'R-cis atracurium). It is three times more potent than atracurium itself and hemodynamically stable thanks to its scarce release of histamine. Cisatracurium is hydrolyzed mainly by the pathway of Hofmann (77%) and to a lesser degree it is metabolized by organ-dependent modes (mainly by the kidney (16%)). Dose therefore hardly needs to be changed for elderly patients or those with liver, kidney or cardiovascular disease. The calculated ED95 is 0.05 mg.kg-1 (0.04 mg.kg-1 in children), although a dose two to four times greater is used under clinical conditions to shorten tracheal intubation time because of low onset of blockade, particularly in comparison with rocuronium. The period of deep blockade (lack of response to neurostimulation) is prolonged by the higher dose, but recovery is dose-independent and recovery indices are similar. Cisatracurium has proven useful in intensive care because of its hemodynamic stability, which is comparable to that of steroid derivatives but with faster recovery from blockade once administration is discontinued. Its metabolism predominantly through Hofmann's pathway, with less laudanosine formation than is produced by atracurium, is also appreciated. Cisatracurium is described as the nondepolarizing muscle relaxant of choice for medium-to-long-term surgery on hemodynamically unstable patients or those with kidney or liver disease, and for neuromuscular blockade in intensive care.     

The comparative study of LUMIWARD immunoassay system and CAP RAST system for determination of specific IgE antibody against mite in infantile atopic dermatitis

The neuromuscular blocking effects and the reversibility of cisatracurium 0.1 or 0.15 mg.kg-1 were compared with those of atracurium 0.5 mg.kg-1 during anaesthesia with propofol, nitrous oxide and isoflurane. Neuromuscular block was monitored using train-of-four stimulation while recording the mechanomyographic response of the adductor pollicis muscle. The block was either allowed to recover spontaneously or was antagonised with neostigmine 50 micrograms.kg-1 at 10% or 25% recovery of the first twitch of the train-of-four. The median times to maximum block were 2.7, 2.2 and 1.5 min following cisatracurium 0.1 and 0.15 mg.kg-1 and atracurium 0.5 mg.kg-1, respectively. After cisatracurium 0.1 mg.kg-1 had been given, the median time to recovery of the train-of-four ratio to 0.8 ('adequate recovery') was 74 min during spontaneous recovery, 48 min after reversal with neostigmine when the first twitch of the train-of-four had returned to 10% of control and 50 min after reversal when the first twitch of the train-of-four had returned to 25% of control. These times for cisatracurium 0.15 mg.kg-1 and atracurium 0.5 mg.kg-1 were 90, 66 and 57 min and 75, 56 and 54 min, respectively. Administration of neostigmine significantly shortened the time to adequate recovery for both drugs but there were no significant differences in the case of either neuromuscular blocking drug between the groups of patients given neostigmine at 10 or 25% recovery of the first twitch of the train-of-four.     

Serotonin syndrome due to an overdose of moclobemide and clomipramine. A potentially life-threatening association

The speeds of onset of pancuronium, atracurium and vecuronium are increased by prior administration of magnesium sulphate. A prospective, randomized, double-blind, controlled, clinical study was performed to examine the effects of prior i.v. administration of magnesium sulphate 60 mg kg-1 on the neuromuscular blocking effects of rocuronium 0.6 mg kg-1 during isoflurane anaesthesia. Neuromuscular function was measured electromyographically (Relaxograph) in 30 patients who received either magnesium sulphate 60 mg kg-1 or normal saline, 1-min before rocuronium 0.6 mg kg-1. Mean onset times were similar in the two groups (magnesium sulphate 71 (SD 20) s; normal saline 75 (23) s), but times to initial, 10% and 25% recovery from neuromuscular block were significantly longer in the magnesium sulphate group (42.1 (16.3), 49.0 (12.4) and 56.5 (13.2) min, respectively) than in the saline group (25.1 (9.1), 33.0 (11.1) and 35.6 (13.2) min, respectively) (P < 0.05 in all three cases). Administration of magnesium sulphate was not associated with adverse haemodynamic effects. Prior administration of magnesium sulphate, under the study conditions described, prolonged rocuronium-induced neuromuscular block but did not increase speed of onset.     

Two circuits to convert short-term memory into long-term memory

In this prospective study we tested the hypothesis that atropine administration, which is known to increase heart rate and cardiac output in infants, will result in a faster onset of neuromuscular block with atracurium. Thirty infants scheduled for elective surgery had anaesthesia induced with nitrous oxide and halothane. Fifteen patients were given atropine and 15 patients acted as controls. All the infants were given atracurium 0.5 mg.kg-1, and neuromuscular block was recorded with the Datex 221 neuromuscular transmission monitor. Although atropine caused an increase in heart rate compared to the control group (median 164 [range 151-182] vs 120 [98-160]min-1 P < 0.0001), there was not a statistically significant difference in the onset of neuromuscular block between the two groups. We conclude that onset of neuromuscular block after atracurium is determined mainly by noncirculatory factors and less by the circulation time to the muscle. The effect of atropine on the time course of neuromuscular block might be different with faster acting neuromuscular blockers.     

Oral clonidine premedication reduces vomiting in children after strabismus surgery

This is a prospective randomized double-blind trial conducted to determine whether preoperative orally administered clonidine causes or potentiates postoperative vomiting in 140 children (3-12 yr) undergoing strabismus surgery. They were all inpatients and classified randomly into four groups (n = 35 each); placebo (control), diazepam 0.4 mg.kg-1, clonidine 2 micrograms.kg-1, and clonidine 4 micrograms.kg-1. These agents were administered 93-112 min (mean; 100 min) before the anticipated time of induction of anaesthesia. All children received inhalational anaesthesia with halothane and nitrous oxide in oxygen. Muscle relaxation in all patients was obtained with vecuronium and residual neuromuscular blockade was antagonized with neostigmine and atropine before tracheal extubation. Diclofenac suppository was prescribed to prevent postoperative pain. No opioids or postoperative antiemetics were administered. All children remained in hospital for two days postoperatively. The incidence and frequency of vomiting were compared in the groups with Kruskall-Wallis Rank test. Clonidine 4 micrograms.kg-1 caused a lower incidence and frequency of vomiting than did placebo and diazepam (incidence and frequency: 11% and 1.37% and 3, and 34% and 2 in clonidine 4 micrograms.kg-1, placebo, and diazepam, respectively; P < 0.05 for clonidine 4 micrograms.kg-1 vs placebo and diazepam). However, low-dose clonidine was ineffective. These data suggest that preanaesthetic medication with clonidine 4 micrograms.kg-1 may be useful for preventing emesis following strabismus surgery. This property of clonidine indicates that it may be superior to other sedative premedicants such as diazepam and midazolam.     

Anxiogenic effect of naltrexone in social interaction test in rats

AIM: To study the anxiogenic effect of naltrexone (Nal) on the emotional state of rats. METHODS: The duration of active interaction was measured in the social interaction test in rats. RESULTS: Without influence on the locomotor activity, Nal (0.1-50 mg.kg-1) dose- and time-dependently decreased the duration of active interaction, which was antagonized by morphine (5 mg.kg-1) or fenclonine (Fen, 150 mg.kg-1 x 3 d) and was enhanced by 5-hydroxytryptophan (5-HTP, 50 mg.kg-1). CONCLUSION: Nal produced anxiety via its blockade of opioid receptors; central opioidergic neurons were involved in the regulation of anxiety through their tonic inhibitions in serotonergic neurons.     

Human retinoic acid (RA) 4-hydroxylase (CYP26) is highly specific for all-trans-RA and can be induced through RA receptors in human breast and colon carcinoma cells

In this article current indications and limitations of neuromuscular monitoring are reviewed. Attention is mainly focused on detection of residual curarisation. New insights in the pathophysiological consequences of residual neuromuscular blockade and the actual criteria of complete recovery are discussed. Surprisingly in this context, despite the benefit of neuromuscular monitoring, its utilisation in clinical practice is rather an exception than the routine. A lack of standardisation of neuromuscular monitoring is probably the major problem on the way to a widespread utilisation of the monitoring.     

Neuromuscular inhibitory effects of propofol evaluated by cat's evoked EMG

Neuromuscular inhibitory effects of propofol were investigated in 7 cats using muscular compound action potential (mCAP) elicited from the gastrocnemius muscle by sciatic nerve stimulation. A rectangular pulse of supramaximal strength and duration of 0.2 msec was applied serially to the sciatic nerve at 0.1 Hz during the experiments, and mCAPs obtained from the gastrocnemius muscle were recorded. After obtaining a constant mCAP amplitude, a series of 8 consecutive mCAPs (M 1-8) evoked by repetitive stimulation at 100 Hz was recorded, and M 8/M 1 amplitude ratio (M 8 amplitude/M 1 amplitude.100%) was calculated as the control value. After control variables had been obtained, initial dose of 2.5 mg.kg-1 of propofol was administered intravenously followed by continuous infusion with incremental dosages of 10, 20, 50 and 100 mg.kg-1.hr-1 of each 30 minute duration. The effects on mCAPs evoked by single and 8 consecutive repetitive stimulation were observed in each period. The depression of single mCAP amplitudes and fading responses in the M 8/M 1 amplitude ratios were not observed at any infusion rate. Our results suggest that propofol has no influence on neuromuscular transmission in cats when administered intravenously at 10 times of human clinical infusion doses.     

Influence of graded changes in vasomotor tone on the carotid arterial mechanics in live spontaneously hypertensive rats

1. The contribution of vasomotor tone to the increased stiffness of carotid arteries in living spontaneously hypertensive rats (SHR) is largely unknown. Whether a reduced vascular tone is associated with an increase or a decrease in arterial stiffness in vivo remains to be determined. The goal of the present investigation was to show that a decrease in vascular tone is associated with a decrease in arterial stiffness, independent of the structural composition of the arterial wall. 2. New high resolution echo-tracking techniques were used to evaluate pulsatile changes of carotid blood pressure and diameter following transient and graded changes of vasomotor tone produced by the dihydropyridine derivative, isradipine. Treatment for 8 weeks was given to groups of SHR rats either with a low (0.6 kg day-1) or a high (2.6 mg kg-1 day-1) dose. Another SHR group received an acute dose of 2.6 mg kg-1 day-1. Results were compared to those of placebo-treated Wystar-Kyoto (WKY) and SHR rats. Whatever the dosage, acute or chronic calcium blockade caused a decrease in blood pressure which was maximal 1 h after administration and disappeared after the 16th h. Carotid arterial thickness and the composition of the arterial wall was determined from histomorphometry. 3. In placebo-treated SHR, the inverse relationship relating blood pressure to carotid arterial distensibility was significantly shifted toward higher values of blood pressure compared to the curve of normotensive placebo-treated WKY rats. The curve of SHR receiving chronically a non antihypertensive (0.6 mg kg-1 day-1) isradipine dose prolonged that of placebo-treated SHR toward lower values of blood pressure, so that carotid distensibility was significantly higher than in WKY for the same diameter and blood pressure level (145 mmHg). With administration of a chronic antihypertensive dose (2.6 mg kg-1 day-1) causing a significant decrease in arterial function. Acute antihypertensive calcium blockade with a single isradipine dose (2.6 mg kg-1 day-1) caused a similar shift in the pressure-distensibility curve toward the WKY curve although the histomorphometric composition of the arterial wall differed significantly from that of chronically treated animals. 4. The study provides evidence that, in living SHR submitted to calcium blockade, (i) a low dose of isradipine causing no substantial antihypertensive effect is associated with a significant elevation of carotid arterial distensibility for the same pressure and diameter as normotensive controls, and (ii) an acute or chronic dose causing a substantial antihypertensive effect is associated with a transient shift of the SHR distensibility-pressure curve toward a physiological arterial function, increasing carotid distensibility for the same pressure and diameter as WKY controls. Since such findings were observed independently of the histomorphometric composition of the arterial wall, they imply that the transient decrease in arterial stiffness produced by calcium blockade should involve specific changes in the connections between arterial smooth muscle and extracellular matrix.     

Anesthetic management of a patient with Cowden syndrome

Cowden syndrome is a rare syndrome of chromosome abnormalities presenting with polyposis of digestive tracts, characteristic skin eruption and neuromuscular disorders. A 56-year-old male patient with Cowden syndrome underwent upper abdominal surgery under general anesthesia followed by post-operative epidural analgesia with buprenorphine. Proposed total gastrectomy was not performed because of massive invasion of carcinoma in the abdominal cavity and gastrojejunostomy was done instead. The anesthesia was satisfactory with inhalation of nitrous oxide and enflurane with intravenous vecuronium. Neuromuscular monitoring with electric twitch-responses of the hand showed normal patterns throughout the anesthesia. The recovery from anesthesia and neuromuscular blockade was prompt. Intermittent epidural buprenorphine, twice a day (0.2 mg of buprenorphine in 9 ml of normal saline for one time) was started just after the recovery of anesthesia and continued for four days. Delirium occurred two days after beginning epidural buprenorphine and disappeared three days after its discontinuation. The patient died 52 days after the operation from obstructive jaundice and sepsis. The delirium, therefore, seems to have been caused by buprenorphine possibly due to its impaired metabolism by the liver. Although we did not experience any abnormal neuromuscular reactions to vecuronium or anesthetic agents, it is important to perform preoperative neuromuscular examinations and peri-operative monitoring in the anesthetic management of a patient with this syndrome.     

Cholinesterases

OBJECTIVE: To review current data on butyrylcholinesterase. DATA SOURCES: Search through Medline data bases of articles in French or English. STUDY SELECTION: Original articles and case reports were selected. Letters to editor were excluded. DATA EXTRACTION: The articles were analyzed in order to obtain current data on biochemical structure, action, major pathological variations, especially with regard to the recent informations obtained by molecular biology concerning the identification of genetic variants. DATA SYNTHESIS: Butyrylcholinesterase must be differentiated from acetylcholinesterase, which cannot hydrolyse succinylcholine. The physiological action of butyrylcholinesterase remains unknown, although it can hydrolyse many drugs. Excluding genetical mutations, several physiopathological situations alter butyryl-cholinesterase activity. Butyrylcholinesterase activity assessment does not allow the diagnosis of genetic variants. Whatever the origin, only deficits of more than 50% modify significantly the metabolism of succinylcholine or mivacurium. The diagnosis of a prolonged neuromuscular blockade is obtained with systematic monitoring of the neuromuscular function in case of administration of mivacurium or succinylcholine. Mivacurium should only be re-injected when one response at train of four is obtained. In case of prolonged neuromuscular blockade, the anticholinesterasic agent should not be administered when no response at train of four is obtained. The biochemical methods using inhibitors (dibucaine, fluoride) of the butyrylcholinesterase and a familial study lead to the diagnosis in most cases because the atypical and fluoride variants are the most frequent. When results are doubtful, genetic molecular methods with the use of PCR and restriction enzymes allow a rapid diagnosis.     

Right ventricular diastolic disfunction and its relation to left ventricular performance in patients with hypertension

The potential effects of propofol emulsion (Diprivan) on the neuromuscular transmission and muscular contraction were studied using in vitro and in vivo nerve-muscle preparations of rats. The contractions of the isolated rat diaphragm elicited by either indirect or direct electrical stimulation were inhibited by propofol emulsion at threshold concentrations of 42 and 112 mumol l-1, respectively. Similarly, the gastrocnemius muscle contractions induced by either indirect or direct electrical stimulation in vivo were inhibited by propofol emulsion administration as a bolus injection of 2.5 mg kg-1 intravenously, followed by intravenous infusion of 150 micrograms kg-1 min-1 for 1 h into rats. The inhibitory effects of propofol in both preparations were greater with indirect rather than direct stimulation. Propofol emulsion was found to be capable of enhancing the paralysis of the indirectly stimulated rat diaphragm in vitro and gastrocnemius muscle in vivo induced by either pipecuronium or succinylcholine. The combination of propofol and pipecuronium led to a synergistic inhibition of the neuromuscular transmission, while the combination of propofol and succinylcholine led to additive inhibition. Pretreatment with propofol emulsion at these threshold concentrations markedly inhibited the stimulant effects of aminophylline and digoxin on the indirectly and directly induced diaphragmatic contractions. Also, the enhancement effects of aminophylline on the indirectly and directly and of digoxin on indirectly induced rat gastrocnemius muscle contractions were markedly inhibited by propofol emulsion administration to rats. Pretreatment with propofol emulsion at the threshold concentrations enhanced the inhibitory effects of verapamil on diaphragmatic contractions elicited either indirectly or directly and enhanced the inhibitory effect of adenosine on the contractions elicited indirectly. Similarly, the inhibitory effects of verapamil on the indirectly and directly and of adenosine on indirectly induced rat gastrocnemius muscle contractions were markedly potentiated by propofol emulsion administration to rats. In addition, doubling the concentration of calcium in the bathing fluid produced no change in the inhibitory effects of propofol emulsion on either indirectly or directly elicited diaphragmatic contractions, while doubling the concentration of external magnesium potentiated the propofol effects. Pretreatment with 4-aminopyridine suppressed the inhibitory effects of propofol emulsion on diaphragmatic contractions elicited either indirectly or directly. These results suggest that propofol acts presynaptically to inhibit the neuromuscular transmission and acts at the muscle membrane to inhibit the muscular contraction.     

Indoor radon prediction from soil gas measurements

We have studied the intubating conditions in 60 ASA I or II patients, after induction of anaesthesia with propofol 2 mg kg-1, allocated to one of the following three groups: group 1, remifentanil 1 microgram kg-1; group 2, remifentanil 1 microgram kg-1 and lignocaine 1 mg kg-1; group 3, remifentanil 2 micrograms kg-1. No neuromuscular blocking agents were administered. Intubating conditions were assessed using a four-point scoring system based on ease of laryngoscopy, jaw relaxation, position of vocal cords, degree of coughing and limb movement. Overall intubating conditions were acceptable in 35% of patients in group 1, 100% of patients in group 2 and 85% of patients in group 3. There was a statistically significant drop in blood pressure after induction in groups 2 and 3, and two patients in each group required ephedrine 6 mg i.v. boluses, as dictated by the intervention criteria (mean arterial pressure fall > 25% from baseline). Similarly, there was a drop in heart rate in groups 2 and 3, but this did not reach statistical or clinical significance, and no patient required atropine.     

Selective ETA receptor antagonism with BQ-123 is insufficient to inhibit angioplasty induced neointima formation in the rat

OBJECTIVE: The aim was to assess whether or not the endothelin ETA receptor selective antagonist BQ-123 could inhibit neointima formation in vivo following balloon angioplasty. METHODS: The effect of either acute administration of BQ-123 (0.1 mg.kg-1.min-1 intra-arterial infusion for 1 h before and 1 h after angioplasty) or chronic administration (bolus intraperitoneal injection, 2.5 mg.kg-1 twice daily; continuous intraperitoneal infusion, 0.8 and 8 mg.kg-1.d-1) on neointima formation was examined in rats which had undergone left common carotid artery balloon angioplasty. RESULTS: Neither acute intra-arterial infusion nor either mode of chronic intraperitoneal administration of BQ-123 had a significant effect on the degree of neointima formation observed following balloon angioplasty. CONCLUSIONS: Neither acute nor chronic ETA receptor blockade is sufficient to inhibit angioplasty induced neointima formation in the rat. Since it was previously shown that the ETA/B antagonist SB 209670 was effective in this model, while the ETA selective antagonist BQ-123 is now found to be ineffective, the data implicate the ETB receptor subtype in the pathogenesis of neointima formation.     

Evaluation of BTS 67 582, a novel antidiabetic agent, in normal and diabetic rats

1. The effect of BTS 67 582, a novel antidiabetic agent, has been evaluated on plasma glucose and plasma insulin in normal and streptozotocin-induced diabetic rats. 2. BTS 67 582 (3 to 300 mg kg-1, p.o.) caused a dose- and time-dependent reduction in plasma glucose and an increase in plasma insulin in both fasted and glucose-loaded normal rats. The ED50 for the glucose lowering effect of BTS 67 582 in fasted rats was 37.6, 18.4 and 18.5 mg kg-1 at 1, 2 and 4 h after administration respectively. 3. In streptozotocin-induced (50 mg kg-1, i.v.) diabetic rats, BTS 67 582 (37-147 mg kg-1, p.o.) caused significant reductions of plasma glucose following a glucose load, whereas glibenclamide (100 mg kg-1, p.o.) was ineffective. BTS 67 582 significantly increased plasma insulin compared to controls whereas glibenclamide did not. 4. BTS 67 582 did not displace [3H]-glibenclamide from its binding sites in rat brain, guinea-pig ventricle or the HIT-T15 insulinoma beta-cell line. BTS 67 582 does not therefore appear to modulate its action via an effect on the 'sulphonylurea' receptor. 5. In fasted rats, the glucose lowering effect of BTS 67 582 (100 mg kg-1 p.o.) and glibenclamide (1 mg kg-1, p.o.) were antagonized by diazoxide (30 mg kg-1, i.p.). In addition BTS 67 582, like glibenclamide, caused a dose-dependent rightward shift of cromakalim-induced relaxation of noradrenaline precontracted rat aortic strips, suggesting the involvement of KATP channels. 6. In summary, BTS 67 582 produces a blood glucose-lowering effect in normal and streptozotocin-induced diabetic rats associated with increased insulin concentrations. This effect appears to be due to a blockade of ATP-sensitive potassium channel activity via a different binding site to that of glibenclamide.     

Esophageal cyst--a rare cause of backache

BACKGROUND: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. METHODS: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg.kg-1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg.kg-1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg.kg-1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. RESULTS: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). CONCLUSION: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.