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PubMed1982

Study on mammal (rat) of the neuro-muscular synapse function under hyperbaric conditions (11 ata): effects of the curarization.

Under hyperbaric conditions (11 ata) obtained with normoxic O2-N2 mixtures spontaneous EMG activity disappears, as do reactions to noise, but this phenomenon is reversible after the substitution of Helium for Nitrogen in the mixture. Analysis of EMG responses to sciatic nerve excitation has revealed no difference between the EMG tracings recorded under normobaric pressure and those obtained under hyperbaric conditions (O2-N2 or O2-He, 11 ata), and hyperbaric conditions do not seem to interfere with neuro-muscular synaptic transmission. Furthermore, the effect of Pavulon (an antidepolarising, acetyl-cholino-competitive curare-mimetic drug) is similar under normal and hyperbaric conditions: hyperbaria change neither the onset of neuro-muscular blockage nor its intensity or duration. The absence of a specific effect on synapse function of a change in the diluting gas from nitrogen to helium suggests that there was no change in post-synaptic receptor function. This result is not in accordance with the hypothesis that inert gas pressures of less than 10 ata modify molecular structures particularly at the neuro-muscular synapse level.

Animals↗
PubMed1995

Perioperative train-of-four monitoring and residual curarization.

It has been suggested that perioperative train-of-four (TOF) monitoring does not reduce the incidence of postoperative residual curarization (PORC). The purpose of this study was to examine whether the use of tactile assessment of the response of the adductor pollicis to supramaximal TOF stimulation of the ulnar nerve at the wrist during anaesthesia affected the incidence of PORC. Thirty-nine ASA I or II surgical patients were studied during thiopentone/fentanyl N2O/enflurane anaesthesia. Pancuronium (70-100 micrograms.kg-1) was used to facilitate tracheal intubation and additional pancuronium increments used to maintain surgical relaxation. The requirement for incremental doses of pancuronium and adequacy of recovery following reversal were assessed according to random allocation, either with (Group A; n = 20) or without (Group B; n = 19) access to TOF monitoring. Patients in the two groups received neostigmine in similar doses (Group A: 53 micrograms.kg-1 (5.9); Group B: 55 micrograms.kg-1 (5.4)). On arrival of the patient to the recovery area, neuromuscular function was assessed electromyographically (using the Datex NMT 221 to measure TOF ratio) and clinically. The incidence of PORC (TOF ratio < 70%) was greater in Group B (47%) than in Group A (15%) (P = 0.029). We conclude that the use of perioperative TOF monitoring decreases the incidence of pancuronium-induced PORC.

Adult↗
PubMed1978

Origin of the neocortically monitored theta rhythm in the curarized rat.

An array of epidural electrodes was acutely implanted in locally anesthetized, curarized rats in order to map the surface distribution of rhythmic slow activity (RSA) which appears within the neocortex. Peak amplitudes (of about 122 muV) were centered over the dorsal hippocampus outline. A laminar profile of RSA recorded within the neocortex indicated no shifts in phase relative to a homotopic, epidural electrode. RSA increased slightly in amplitude (mean increase = 53%) at the deepest level or neocortex, but it did not approximate an amplitude peak or null within the neocortex. Multiple-unit activities within the neocortex were not phase-locked to RSA. On the other hand, all of these manifestations of an RSA generator were observed as electrodes passed into the dorsal hippocampus. A unilateral cortical spreading depression (CSD) treatment, which markedly attenuated barbiturate spindles in all subjects (N = 10), usually (N = 7 of 10) had no effect on the neocortically monitored RSA. Dissociations between depressed and non-depressed hemispheres, and between neocortical and hippocampal RSA, were obtained in some subjects during CSD. However, concurrent dissociations were also apparent between recording sites within the hippocampus. It is concluded that the neocortical RSA of rats is passively spread from the underlying hippocampus, and dissociations in neocortical and hippocampal RSA in the rat are secondary to changes in the organization of multiple generators of hippocampal RSA.

Animals↗
PubMed2004

[Curarization for contributing symptomatic treatment of myoclonic jerks induced by chloralose poisoning].

Chloralose poisoning especially leads to consciousness failure and hyperexcitability with typical myoclonic jerks. In an observation of chloralose poisoning by ingestion of synthetic substance against moles, curarization by cistracurium besylate was proposed to contribute in the symptomatic treatment of myoclonus syndrome induced by chloralose poisoning and resistant to a large dose of diazepam.

Adult↗
PubMed1998

Studies on curare-like action of the tripeptide carbobenzoxy-Gly-Gly-Arg-beta-naphthylamide in mouse diaphragm.

The effects of several protease substrates or protease inhibitors on neuromuscular transmission in the isolated mouse phrenic nerve-diaphragm were studied. N-Carbobenzoxy-Gly-Gly-Arg-beta-naphthylamide (Z-GGR-N) but none of the other agents inhibited the nerve-evoked muscle contractions. By means of electrophysiological studies, Z-GGR-N was found to inhibit the amplitudes of both end-plate potentials (epps) (IC50 approximately 50 microM) and miniature end-plate potentials (mepps) but to increase the frequencies of mepps. This tripeptide could protect the nicotinic acetylcholine receptor from the irreversible inhibitory action of alpha-bungarotoxin on the mouse diaphragm. Similar to D-tubocurarine, Z-GGR-N induced tetanic fading both of nerve-evoked muscle contractions and of the amplitude of epps. Furthermore, Z-GGR-N exhibited a greater depression of the amplitudes of train-epps than those of mepps, similar to that of hexamethonium and D-tubocurarine, indicating an effect on presynaptic autoreceptors. Suramin, which could competitively reverse the inhibitory effects of non-depolarizing relaxants, acted in this study as an antagonist of all the effects of Z-GGR-N, especially those at the presynaptic site. All of these findings suggest that Z-GGR-N is a novel tripeptide possessing curare-like actions at both presynaptic and postsynaptic sites and that these actions are independent of its protease substrate property.

Animals↗
PubMed2002

Quinolizidine alkaloids from the curare adjuvant Clathrotropis glaucophylla.

The bark of Clathrotropis glaucophylla (Fabaceae) is used as admixture of curare arrow poison by the Yanomami; Amerindians in Venezuela. A new quinolizidine alkaloid (QA), (-)-13alpha-hydroxy-15alpha-(1-hydroxyethyl)-anagyrine [(-)-clathrotropine], was isolated from the alkaloid extract of C. glaucophylla bark, together with eleven known QAs: (-)-anagyrine, (-)-thermopsine, (-)-baptifoline, (-)-epibaptifoline, (-)-rhombifoline, (-)-tinctorine, (-)-cytisine, (-)-N-methylcytisine, (-)-lupanine, (-)-6alpha-hydroxylupanine and (+)-5,6-dehydrolupanine. The isolation and structure elucidation were performed with the aid of chromatographic (TLC, HPLC and CC) and spectroscopic (UV and 1D/2D NMR) methods, and mass spectrometry. To our knowledge, this is the first time quinolizidine alkaloids have been isolated from an arrow poison ingredient. It is also the first report on Clathrotropis species being used for preparation of arrow poison.

Alkaloids↗
PubMed1984

[Emergency translaryngeal ventilation with a Tuohy needle. Use in case of an inability to intubate and ventilate a curarized patient].

Intermittent translaryngeal insufflations of oxygen at high pressure by a needle could be a life-saving procedure, especially in a patient whose trachea the anesthesiologist was unable to intubate or ventilate. This study was designed to evaluate the quality of translaryngeal ventilation performed with a 16-gauge Tuohy needle and an oxygen pressure of 3 bar (300 kPa) in comparison with an usual plastic cannula of the same calibre. The studies carried out in the laboratory have shown a distinct advantage over the conventional cannula. Whereas an O2 jet delivered by a straight cannula impinged on the posterior wall of the larynx and trachea, the curved tip of the Tuohy needle deflected the axis of the O2 flow emerging from it, which then lay parallel to the longitudinal axis of the trachea. Consequently, gas flow through a simulated trachea was increased (2610 ml X s-1 vs 1240 ml X s-1), the inflation pressure being higher and the tidal volume larger. Moreover, the likelihood of injury to the posterior wall of the airway was reduced; the Tuohy needle held with a clamp close to the skin was more stable in position. Blood gases and clinical data obtained in 10 anesthetized and curarized patients without airway obstruction made it clear that translaryngeal insufflations with a 16-gauge Tuohy needle provided adequate ventilation (PaO2 values between 174 and 851 mmHg, PaCO2 between 38 and 64 mmHg). It was concluded that this technique was an efficient alternative in case of an inability to intubate a patient in apnea.

Blood Gas Analysis↗
PubMed2001

Stereocontrolled synthesis of cis-dibenzoquinolizine chlorofumarates: curare-like agents of ultrashort duration.

The quaternizations of dibenzoquinolizines 9 and 14 with 3-halo-1-propanols are highly cis-selective (94-100% cis), results consistent with the N-methylation of O-methylcapaurine (7b), but in contrast to the proposed trans-stereochemistry of dibenzo[a,h]quinolizine methiodide 10 and the analogous quaternizations of 1-benzyl- and 1-phenylisoquinoline congeners 5b and 5c. In this report, we describe stereoselective preparation of the unique cis-dibenzoquinolizinium propanols 15 and 16and their transformation into bis- and mixed-onium chlorofumarates 19, 20ab, and 26. Dibenzo[a,g]quinolizinium propanol 15 was prepared enantioselectively in three steps from dihydroisoquinoline 11. Asymmetric transfer hydrogenation of 11 in the presence of triethylamine/formic acid and Noyori's chiral ruthenium catalyst 12 produced R-(-)-5',8-dimethoxynorlaudanosine (13) in 98% yield and 87% ee. Pictet-Spengler cyclization of 13 in formalin/formic acid afforded the dibenzo[a,g]quinolizine 14 in 65% yield. Quaternization of 14 with 3-chloro-1-propanol under Finkelstein conditions generated cis-dibenzoquinolizinium propanol 15 in 85% yield with >94% cis-selectivity. The cis-dibenzo[a,h]quinolizinium propanol 16 was obtained as a single stereoisomer by reaction of the known tetramethoxyquinolizine 9 with neat 3-iodo-1-propanol. Bis-onium chlorofumarates 18 and 19 and the mixed-onium derivative 20ab were prepared by a pool synthesis procedure from (1R)-trans-6a, 16, and chlorofumaryl chloride (17). Mixed-onium alpha-chlorofumarate 26 was synthesized from (1S)-trans-6d, 15 and (+/-)-trans-2,3-dichlorosuccinic anhydride (22), employing a recently disclosed chlorofumarate mixed-diester synthesis. The title compounds (19, 20ab, and 26) displayed curare-like effects of ultrashort duration in rhesus monkeys.

Animals↗
PubMed1976

Peripheral heat as a reward for heart rate response in the curarized rat.

It is generally assumed that the mechanical perception of shivering is necessary for the perception of cold discomfort. Shivering of rats in a cool environment was eliminated by curarization. The rats were kept alive by artificial respiration. Heart rate was proportional to rectal temperature in a group of controls. One group of rats was conditioned to increase heart rate to trigger an infrared lamp; another group was conditioned to decrease heart rate to obtain heat. When compared with the results of the control group without infrared heat reward, the results obtained from the two heart-rate-modifying groups show that shivering is not a necessary signal to determine thermoregulatory behavior in rats and, presumably, cold discomfort in man.

Animals↗
PubMed1975

Evaluation of RX 72601 as an anti-curare agent.

RX 72601, a new and potent anticholinesterase, has been evaluated for its ability to reverse the neuromuscular blockade induced by non-depolarizing muscle relaxants. In rats RX 72601 10 mug/kg i.v. proved effective in reversing the effects of alcuronium gallamine, pancuronium or tubocurarine and the drug exhibited a wide margin of safety. RX 72601 proved equally effective in reversing the effects of tubocurarine in both cats and baboons. In dogs and cats, effective anti-curare doses had little action on the cardiovascular or respiratory systems. Overall the results obtained indicate that RX 72601 may be a safe antagonist of non-depolarizing muscle relaxants and that it will be possible to use RX 72601 without prior administration of atropine.

Animals↗
PubMed2000

Residual curarization in the recovery room after vecuronium.

We have investigated residual block after anaesthesia which included the use of the neuromuscular blocking agent vecuronium but no anticholinesterase, in 568 consecutive patients on admission to the recovery room. The ulnar nerve was stimulated submaximally using TOF stimulation (30 mA). Postoperative residual curarization was defined as a TOF ratio < 0.7. Of the 568 patients, 239 (42%) had a TOF < 0.7 in the recovery room. These patients had received a larger cumulative dose of vecuronium than patients who had full recovery (mean 7.7 (SD 3.6) mg vs 6.2 (2.7) mg; P < 0.05) and a shorter time had elapsed since the last vecuronium dose (117 (70) min vs 131 (80) min; P < 0.05). Of 435 patients whose trachea was extubated, 145 (33%) exhibited inadequate recovery from neuromuscular block. Six of these had one or no response to TOF stimulation and were reintubated. In the remaining 139 patients, neuromuscular block was successfully antagonized. Only 20 patients (3.5%) remembered TOF stimulation when questioned 2 h later in the recovery room, and discomfort associated with it was assessed using a visual analogue scale before discharge. We conclude that it is necessary to antagonize residual block produced by vecuronium.

Adolescent↗
PubMed1981

Relationship between respiratory muscle strength and vital capacity during partial curarization in awake subjects.

To determine the relationship between respiratory muscle strength and changes in normal vital capacity (VC), graded levels of muscle weakness were produced in six healthy supine male subjects by four successive doses of d-tubocurarine (0.05 mg/kg each). The maximal effect of d-tubocurarine abolished hand-grip strength and ability to sustain head lift for 5 s, but VC was decreased to only 66 +/- 3 per cent of control. At each level of weakness decreases in VC were significantly less than were decreases in respiratory muscle strength (RMS) monitored by maximum static inspiratory and expiratory pressures. The first dose decreased RMS to 86 +/- 3 per cent of control, but VC was unchanged. Following the second dose,, VC (97 +/- 4 per cent). The VC after the third dose was still 85 +/- 3 per cent of control, while RMS had decreased to 58 +- 2 per cent. Following the final dose of d-tubocurarine (cumulative total 0.20 mg/kg), RMS was 39 +/- 2 per cent of control, compared with VC, 66 +/- 3 per cent of control. The relationship between VC and RMS was curvilinear and conformed to predictions based on the static mechanical characteristics of the normal respiratory system. These findings demonstrate that while VC is relatively spared during partial curarization, this sparing of VC does not indicate a similar extent of preserved RMS. Rather, it reflects the relative ease with which weakened respiratory muscles are able to drive the normal respiratory system in the supine subject. The same weakened muscles may be unable to generate sufficient force to handle mechanical challenges such as coughing and vomiting.

Adult↗
PubMed1980

Total body and splanchnic thermogenesis in curarized man during a short exposure to cold.

To investigate thermoregulation independent of muscular contractions in adult man during a short period of exposure to cold, five examinations were carried out on four individuals who were unconscious due to persistent brain damage and who were totally curarized during the exposure. An increase was found in total body oxygen consumption of 0.043 mmol . kg-1 (range 0.038-0.049) or 25%, in plasma noradrenaline of 5.05 nmol . 1-1 (range: 2.48-6.73) or 132%, and in plasma non-esterified fatty acids of 0.6 mmol . -1 (range: 0.049-0.095) or 44%. No changes occurred in plasma adrenaline or plasma glucose. Splanchnic oxygen consumption increased and contributed significantly to that of the total body in only one of the four cases. These results indicate that regulatory nonshivering thermogenesis exits in adult man not acclimatized to cold, that it is mediated by noradrenaline, that the major fuel substrate for the increased energy demand is the triglycerides from the fat stores, and that the splanchnic area contributes only irregularly and to a small degree to this part of thermogenesis.

Adult↗
PubMed1975

Interaction of competitive antagonists: the anti-curare action of hexamethonium and other antagonists at the skeletal neuromuscular junction.

1. In the rat isolated diaphragm preparation hexamethonium and other low potency competitive antagonists of acetylcholine (ACh), including gallamine and hyoscine butylbromide, reverse block by the potent antagonists tubocurarine, pancuronium and alcuronium. 2. In the presence of tubocurarine, hexamethonium increases the amplitude of the end-plate potential without increasing the quantal content. It enhances the response to ACh applied iontophoretically to the end-plate but does not enhance the response to ACh applied in the bath. 3. The anti-curare effect of hexamethonium is abolished in the diaphragm of the rat, guinea-pig and mouse by inhibitors of acetylcholinesterase. The effect is not observed in the indirectly stimulated toad sartorius muscle. 4. The effect is explained if tubocurarine does not dissociate appreciably in the time taken for ACh to achieve high occupancy of receptors, so that a fraction of receptors is completely excluded from occupation by ACh. Equilibration with hexamethonium reduces the fraction excluded by tubocurarine and the transmitter now competes with hexamethonium for more receptors and produces a larger response. 5. On the basis of this explanation the half-time for dissociation of tubocurarine must be about 1 millisecond. It follows that tubocurarine does not act competitively with ACh at synapses when transmitter action is sufficiently brief, and that its binding to the receptor is probably diffusion-limited.

Acetylcholine↗
PubMed1979

Effects of 2,4-dinitrophenol amylobarbitone and certain other drugs on the rate of oxygen consumption and force of contraction of isolated curarized diaphragm muscle of the rat.

1 A technique has been developed for studying over periods of 10 min or longer the effects of drugs on both the force of electrically-induced contractions and the oxygen consumption of an isolated, curarized, mammalian, skeletal muscle preparation.2 The resting oxygen consumption of the muscle was increased substantially by 2,4-dinitrophenol in concentrations (0.02 mM and higher) that eventually produced contracture. Two other uncoupling agents, 4,6-dinitro-o-cresol and carbonylcyanide-p-trifluoromethoxyphenylhydrazone, behaved similarly.3 The oxygen consumption over 10 min of the stimulated muscle was also increased by 2,4-dinitrophenol (0.05 mM), although the strength of the ;maximal' contractions was lessened.4 Amylobarbitone increased the strength of contraction at a concentration (0.2 mM) that did not affect oxygen consumption significantly. Amylobarbitone and pentobarbitone also increased it at a concentration (1 mM) that depressed oxygen consumption. They decreased both strength of contraction and oxygen consumption at a concentration of 5 mM. Phenobarbitone had a weaker action.5 S-n-decyl-thiouronium increased oxygen consumption when given at a concentration (1 mM) that diminished strength of contraction and eventually produced contracture of the muscle.6 Both S-methyl-thiouronium (1 mM) and 4-aminopyridine (0.1 mM and 0.5 mM) increased strength of contraction without increasing oxygen consumption. Neither strength of contraction nor oxygen uptake was affected by ouabain (up to 0.01 mM) or by phenformin (0.1 mM).7 It is concluded that the response to 2,4-dinitrophenol is due mainly, if not wholly, to its known ability to uncouple oxidative phosphorylation; that the response to the barbiturates is due to a combination of a known metabolic action (viz., blocking of the respiratory chain) and a stimulant action on muscle; and the response to S-n-decyl-thiouronium to a disruptive action on cell membranes. The disproportionate actions of 4-aminopyridine and S-methyl-thiouronium on strength of contraction relative to oxygen consumption are also attributed to a non-metabolic action.

Amobarbital↗
PubMed1980

Curare-like effect of propranolol on rat extraocular muscles.

1 The effects were studied of the beta-adrenoceptor blocking drug, (+/-)-propranolol and its (+)- and (-)-isomers on contractility of rat isolated diaphragm and inferior rectus muscles. 2 Propranolol (10(-5) M) did not modify the resting tension nor the electrically-induced twitch contraction in diaphragm and extraocular muscles, nor the tonic tension evoked in the latter by high K concentrations. 3 In inferior rectus preparations (+/-)-propranolol (5 x 10(-6) M) reduced significantly tensions evoked by succinylcholine (SCh). Cumulative dose-response curves to SCh were shifted to the right in a nearly parallel manner by (+)- and (-)-propranolol which were about equiactive. 4 It is concluded that the depressant action of propranolol is independent of its adrenoceptor blocking potency and it is not due to an alteration of the contraction mechanism. Propranolol appears to depress SCh-evoked tensions through a curare-like effect on cholinoceptors.

Animals↗
PubMed1978

The effects of pH and curare on the time course of end-plate currents at the neuromuscular junction of the frog.

1. The effect of pH changes on synaptic currents has been analysed by external recording of the miniature end-plate currents (m.e.p.c.s) or by recording in voltage-clamped end-plates the current elicited by nerve stimulation (e.p.c.). 2. Changes in pH do not appreciably effect the peak amplitude of the current produced by a single quantum or by short ionophoretic pulses of acetylcholine. 3. The time constant of decay of the m.e.p.c.s is prolonged by about 50% in acid pH and shortened by about the same amount in alkaline pH. This effect is independent of the cholinesterase activity of the end-plate. 4. In curarized preparations the decay of the e.p.c. is shorter than in Mg-blocked end-plate even in the absence of cholinesterase blocking agents. 5. The action of pH on the decays can be explained by a titration of the surface charges of the membrane which effects the voltage dependent reaction that controls the rate of closing of the synaptic channels.

Animals↗