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PubMed1987

Muscle blood flow and fiber activity in partially curarized rats during exercise.

We previously reported that low doses of d-tubocurarine attenuated glycogen loss in red muscles of rats during treadmill walking but that the initial hyperemia in the muscles was normal. The present studies were performed to 1) determine with electromyography (EMG) whether red muscle fiber activity is reduced in walking, curarized rats and 2) study muscle blood flow and glycogen loss during running with different doses of curare (dose response). At 0.5 min of treadmill walking (15 m/min), integrated EMG in vastus intermedius (VI) muscle was reduced by an average of 18% in curarized (60 micrograms/kg) rats, although blood flow (measured with microspheres) was the same as in saline control rats. Comparison of blood flows and glycogen loss in quadriceps muscles at 1 min of treadmill running (30 m/min) with different curare doses (20-60 micrograms/kg) demonstrated that red muscle glycogen loss was inversely related to curare dose but that blood flows in the same muscles were unaffected by curare. These findings provide support for our previous conclusion that at the initiation of low to moderate treadmill exercise, red muscle blood flow is not proportional to the activity or metabolism of the muscle fibers.

Animals↗
PubMed1983

Block of glutamate-activated synaptic channels by curare and gallamine.

Excitatory junctional currents (e.j.cs) and glutamate-activated currents have been examined in voltage-clamped locust muscle fibres exposed to curare or gallamine. Although these drugs have little action on channel kinetics at the resting potential, there is an increasingly pronounced effect at hyperpolarized levels. In the presence of curare (5-100 microM), fibres held at hyperpolarized potentials showed e.j.cs with an initial 'fast component' followed by a 'slow tail'. In many fibres, hyperpolarization beyond -50 mV decreased the amplitude of the peak synaptic current; the decay time constant of the fast component was decreased by hyperpolarization while the time constant of the slow component was increased. Iontophoretic application of brief pulses of glutamate also produced two-component glutamate currents in these conditions. Gallamine was considerably more effective than curare, markedly altering the decay time and amplitude of the e.j.c. and the glutamate current at 1-5 microM. Its effects appeared qualitatively similar to those of curare. The observations are consistent with the idea that curare and gallamine produce a transient block of glutamate-activated synaptic channels.

Animals↗
PubMed1975

Study of sensitivity to curare in certain neurological disorders using a regional technique.

A regional technique for the study of curare sensitivity has been applied to patients with Duchenne type muscular dystrophy, myotonic disorders, certain lower motor neurone disorders, to patients with weakness in the arm after hemiplegia, to patients with hyper-reflexia and hypertonia without weakness, and to Parkinsonism. In the dystrophy patients, sensitivity to curare differs from normal controls in that the neuromuscular block persists. The possibilities that this latent defect of neuromuscular transmission is the result of acetylcholine deficiency due to a prejunctional defect or the result of alterations in the property of the postjunctional membrane are discussed. In the myotonic and lower motor neurone disorders, curare sensitivity was similar to that of normal controls. After hemiplegia, the affected side shows resistance to curare when compared with the unaffected side. In states of hyper-reflexia and hypertonia, however, the sensitivity to curare is greater than in normal controls. In Parkinsonism, sensitivity is similar to that of the controls. The results in upper motor neurone lesions are discussed in relation to the dependence of neuromuscular transmission upon the motor neurone, which, in turn, is dependent upon descending impulses.

Action Potentials↗
PubMed1985

Muscle blood flow patterns during exercise in partially curarized rats.

We studied the distribution of blood flow within and among muscles of partially curarized (40-100 micrograms/kg body wt) rats during preexercise and at 1 min of low-speed treadmill exercise (15 m/min). Glycogen loss in the deep red muscles and parts of muscles was significantly reduced in the curarized animals during exercise, indicating the fibers in these muscles were recruited to a lesser extent and/or had lower metabolisms than fibers in the same muscles of control rats. However, elevations in blood flow in the red muscles of the curarized rats were as great or greater than those in the control rats. Thus reduced recruitment and/or metabolism of the deep red muscle fibers of the curarized animals was not accompanied by reduced blood flow. These findings suggest a dissociation between red fiber metabolism and blood flow in the curarized rats during the 1st min of slow treadmill exercise and indicate that release of vasodilator substances or local physical factors associated with muscle fiber activity are not solely responsible for the initial hyperemia during exercise.

Animals↗
PubMed2005

[Does evidence lead to a change in clinical practice? Danish anaesthetists' and nurse anesthetists' clinical practice and knowledge of postoperative residual curarization].

BACKGROUND: Recent studies have shown a high incidence of postoperative residual curarization (PORC). The reason for this is unclear. The purpose of this study was to evaluate whether the methods used by Danish anaesthetists to exclude PORC are evidence-based and, if they are not, to determine the reasons why. METHODS: 251 anaesthetists (nurses and physicians) from eight different hospital anaesthetic departments completed a questionnaire concerning their knowledge about and clinical practice of residual curarization. RESULTS: All of the 251 participants filled in the questionnaire. 91% underestimated the incidence of PORC after the administration of intermediate-acting muscle relaxants, and 27% incorrectly believed that it is always possible to exclude PORC using clinical tests. Only 45% knew that the train-of-four ratio must exceed 0.9 to exclude residual curarization, and only 25% knew that clinically significant residual curarization cannot be excluded by tactile/visual evaluation of the response to train-of-four nerve stimulation. 91% had access to a nerve stimulator, 85% with the option of objective monitoring. 13% used a nerve stimulator seldom or never. The overall attitude toward using nerve stimulators was positive. CONCLUSION: The results indicate that Danish anaesthetists" clinical practice regarding residual curarization is often not evidence-based. The reason for this seems to be a lack of knowledge, rather than lack of resources and/or a negative attitude toward neuromuscular monitoring.

Anesthesia Recovery Period↗
PubMed1975

[Variations in the activity of various curarizing substances as a function of the time of administration].

This experiment was carried out upon the male-adulte-AF SPF-Wister Rat, anesthetized by the use of pentobarbital-Na at the only dosage of 40 mg/kg/IP and put under artificial ventilation. The animals were divided into two groups: Group I, "diurnal animals" curarized between 10 a.m and 4 p.m; Group 2, "nocturnal animals" curarized between 9 and 12 p.m. Four drugs of the curarimimetic (pachycurare, non-depolarizing) type: gallamine, D-tubocurarine, pancuronium and AH-8165 were studied at doses presenting the same activity. The total curarizing effect measured by the surface defined by the curve of curarization within ten mns was constantly and significantly lowered in "nocturnal animals": a 25 p. 100 diminution with gallamine, 20 p. 100 diminution with D-tubocurarine, 27 p. 100 diminution with pancuronium, 19 p. 100 diminution with AH-8165. The hypothesis is that this diminution in the action of curarizing substances may be, to a great extent, in keeping with the rise of their metabolism -- the hepatic enzymatic activity being, in the rat, a nocturnal animal, definitely increased during the night.

Animals↗
PubMed1951

Experiments on the role of potassium in the blocking of neuromuscular transmission by curare and other drugs.

1. Experiments with perfused frog muscles and with isolated frog muscles immersed in Ringer's solution have failed to show any effect of curare in liberating potassium from muscle tissue. This makes it difficult to suppose that the paralytic effect of curare can be attributed to cation exchange between curare and K whereby a labile potassium compound needed for stimulation is removed from the neuromuscular junction. 2. Similar negative results were obtained with dihydro-beta-erythroidine and myanesin. 3. A small liberation of K from perfused muscle does result from treatment with acetylcholine. This is probably due to the contracture of the muscle since the effect is largely eliminated by previous treatment of the muscle with curare. The amount of potassium lost in this way from perfused muscles is too small to detect when muscles are analyzed after immersion in Ringer's solution with and without acetylcholine. It is concluded that there is no significant cation exchange between acetylcholine and K in muscle, but only a small loss of K due to the contracture produced by the acetylcholine.

Acetylcholine↗
PubMed1984

Curare-induced transformation of myosin pattern in developing skeletal muscle fibers.

The effects of neuromuscular block on the pattern of distribution of myosin isozymes in developing skeletal muscle fibers was examined by immunocytochemistry. The homogeneous population of fibers in the anterior latissimus dorsi (ALD) of the 18-day chick embryo was converted by curare to a mosaic of at least two categories of fibers. Normally all fibers in this slow muscle reacted with antibodies against slow myosin (anti-ALD). They also reacted with an antibody specific for the alkali 1 light chain (anti-delta 1) but not the alkali 2 light chain (anti-delta 2) of fast myosin. After treatment with curare, which inhibits neuronal cell death and increases the number of axonal endings, ALD muscle fibers continued to react with anti-delta 1, but many now reacted with anti-delta 2 as well. The same fibers failed to react with anti-ALD. From this it can be concluded that the myosin in this population was converted to a type not normally present. The changes, therefore, are not merely a result of the preferential loss of a slow type of fiber, nor are they a result of delayed maturation. In contrast, curare had no apparent effect on the fast posterior latissimus dorsi (PLD). As in the normal muscle at 18 days, all fibers reacted strongly with anti-delta 1 and to variable degrees with anti-delta 2, and very few fibers reacted with anti-ALD. Our observations suggest that the dual response to antibodies against fast and slow myosin during development is not a necessary consequence of multiple axon terminals. We present evidence that curare induces the expression of a different myosin in the embryonic ALD, and we suggest that the selective transformation of the fiber population may be a manifestation of a change in composition of the motoneuron pool.

Animals↗
PubMed1992

War and hunting poisons of the New World. Part 1. Notes on the early history of curare.

The history to about 1850 of the muscle-relaxant poison curare is discussed, especially the developments leading to the botanical identification of the plants that yield the alkaloidal active principles: Loganiaceae (Strychnos species) and Menispermaceae (Abuta, Chondrodendron, and Curarea species). One of the earliest encounters with the poison appears to have been during the exploration of the Lake Maracaibo region in Colombia by Alonso Pérez de Tolosa in 1548. It is pointed out (yet again) that Sir Walter Ralegh did not bring back the poison to Europe in 1595 and that it was Keymis who first came across the word ourari when exploring the lower reaches of the Orinoco in 1596. Gumilla, La Condamine, Ulloa, Veigl, and others gave much additional information about the poison during the 18th century. Scientific studies began in the latter part of the century when Schreber listed the botanical identities of four of the plant components entering into the curare prepared by the Akawai Indians of Surinam. As far as is known, none of these people actually saw curare being made. Thereafter, progress was rapid. Humboldt and Bonpland were the first trained scientists to witness the preparation of the poison, at the very beginning of the 19th century. Subsequent exploration by Martius and Spix, Poeppig, Youd, the Schomburgk brothers, De Castelnau and Deville, Spruce, and others, up to the middle of the century, extended and deepened botanical and ethnological knowledge of curare. Study of its physiology started at about that time with the classical experiments of Rudolf von Koelliker and Claude Bernard.

Curare↗
PubMed1977

Quantitative analysis of d-tubocurarine chloride in curare by column liquid chromatography.

An improved quantitative analysis of d-tubocurarine chloride in the plant extract curare is presented. Gradient high-performance liquid chromatography on a hydrophobic stationary phase was found to be very suitable for the analysis of quaternary ammonium bases such as the complex mixture of curare alkaloids. Owing to the residual free silanol groups on the modified silica surface, the curare alkaloids are eluted from a reversed-phase column only if an electrolyte is added to the mobile phase. In order to optimize the separation, the effects of pH, the nature of the cation in the buffer and the concentration of the buffer of the retention of the alkaloids were investigated. Using a tetramethylammonium phosphate buffer at pH 4 in a gradient of water-methanol, undesirable retardation effects on the reversed-phase column could be suppressed sufficiently. As a result, an accurate method for the determination of d-tubocurarine chloride in curare was obtained. The coefficient of variation of this analysis is only 1.3%.

Chromatography, High Pressure Liquid↗
PubMed1982

Curare can open and block ionic channels associated with cholinergic receptors.

Curare has long been regarded as a typical competitive antagonist of acetylcholine (ACh) at the vertebrate neuromuscular junction. Recently, however, it has been shown that curare can also block the channels opened by ACh at the frog neuromuscular junction as well as on rat and Aplysia neurones; moreover, curare is able to depolarize rat myotubes and thus behaves as an agonist for the cholinergic receptor of this preparation (see ref. 6). Using the single channel recording technique, we have now found that, on rat myotubes, curare can both open and block in the same cell the channels controlled by the cholinergic receptor.

Acetylcholine↗
PubMed1976

Electrophysiologic diagnosis of myasthenia gravis and the regional curare test.

Two hundred and fifty consecutive patients were evaluated for myasthenia gravis with repetitive supramaximal stimulation of peripheral nerves and regional curare administration when necessary. Among patients with definite generalized myasthenia gravis, 72 percent had abnormal responses to repetitive supramaximal stimulation alone and another 17 percent had abnormal responses after regional curare administration. Among those with possible generalized myasthenia gravis, 15 percent had abnormal responses to repetitive supramaximal stimulation and another 12 percent had abnormal responses after regional curare administration. Of those with only ocular symptoms, 46 percent had abnormal responses to repetitive supramaximal stimulation before or after regional curare administration, suggesting generalized involvement. Myasthenia gravis has not developed subsequently in any of the equivocal patients with negative electric tests. We have found these electric procedures to be simple, safe, and at least as effective as other methods in diagnosing myasthenia gravis.

Curare↗
PubMed1993

Selective enhancement of the interaction of curare with the nicotinic acetylcholine receptor.

Alteration of the ligand-binding domain of the nicotinic acetylcholine receptor through site-directed mutagenesis offers a powerful approach to the elucidation of structure-function relations in the receptor. Several conserved tyrosine residues in the large extracellular amino terminus of the alpha subunit of the receptor have been implicated by both chemical labeling and mutagenesis studies as playing an important role in the interaction of acetylcholine with the receptor. We and others have previously shown that substitution of phenylalanine for tyrosine at position 198 of the alpha subunit (alpha Y198F) leads to a rightward shift in the dose-response curve for acetylcholine-elicited currents. We have further investigated this particular mutation by examining the interaction of the competitive antagonist d-tubocurarine (curare) with the receptor. In contrast to the effect on the interaction of agonists with the receptor, this mutation leads to a marked increase in the affinity of the receptor for curare. Furthermore, this enhancement in affinity is selective for curare and is not seen with other competitive antagonists (pancuronium, beta-erythroidine, and gallamine). Examination of the structures of these competitive antagonists leads to the proposal that this enhancement is due to the formation of an aromatic-aromatic interaction between the phenylalanine ring at position alpha 198 in the mutant and one of the aromatic rings of curare and that this can provide information about the spatial arrangement of this residue in the binding site.

Alkaloids↗
PubMed1976

Hippocampal theta rhythm. I. Depth profiles in the curarized rat.

Systemic injection of curare changes the depth profile of theta rhythm seen in the hippocampus of the freely moving rat. Under curare, dorsoventral microelectrode advancement reveals the presence of a sudden phase reversal and null occurring at the level of the stratum radiatum of CA1. Further advancement reveals the presence of an amplitude peak in the vicinity of the hippocampal fissure. In addition to the change in depth profile, curare alters the relationship between the amplitudes of the two phasereversed components of the theta rhythm. The change in theta rhythm brought about by curare outlasts the paralytic effect of the drug.

Animals↗
PubMed1977

Changes in motor commands, as shown by changes in perceived heaviness, during partial curarization and peripheral anaesthesia in man.

1. The centrally generated ;effort' or direct voluntary command to motoneurones required to lift a weight was studied using a simple weight-matching task when the muscles lifting a reference weight were weakened. This centrally generated input to motoneurones was increased when the lifting muscles were partially paralysed with curare or decamethonium as judged by the increased perceived heaviness of a reference weight lifted by the weakened muscles.2. If subjects were asked simply to make matching isometric contractions when the lifting muscles were weakened the isometric tension produced by a weakened muscle was over-estimated.3. When subjects matched weights by flexing the distal joint of the thumb the perceived heaviness of a reference weight during a control partial curarization was compared with its perceived heaviness during a similar partial curarization when the thumb was also anaesthetized. At any level of maximal strength during curarization the perceived heaviness (which reflects the motor command to lifting motoneurones) was increased when the thumb was anaesthetized.4. This increased voluntary command to lifting motoneurones may be required because automatic reflex assistance provided by apparent servo action from the long flexor of the thumb is suppressed by anaesthesia of the thumb (Marsden, Merton & Morton, 1971, 1973, 1976a; Dyhre-Poulsen & Djørup, 1976).

Anesthesia, Local↗
PubMed1990

[Seasonal changes in neuromuscular transmission in experiments on dissected or curarized frog muscles].

The end-plate currents and potentials (EPCs and EPPs) in cut or curarized muscles were investigated in frogs maintained at different temperatures (5 and 20-25 degrees C) before experiments in summer and in winter. EPCs and EPPs were elicited by nerve stimulation with different frequencies (1 and 100/s). Seasonal changes in amplitude, facilitation and depression of the EPPs and EPCs observed in curarized and cut (not curarized) muscles differed quantitatively and qualitatively. These differences may be explained assuming that sensitivity of the neuromuscular junction to the curare action (probably, a presynaptic one) is season-variable.

Animals↗
PubMedDate not supplied

A new regional curare test of the elbow flexors in myasthenia gravis.

Electrical and mechanical responses of the elbow flexors (EFs) and the adductor pollicis muscle (ADP) were evoked in 31 patients with myasthenia gravis (MG). Thirteen patients with moderate or severe involvement showed a decrement during trains of repetitive stimuli in both muscle types, greater in the proximal ones than in the distal one. Seven of 18 patients with mild generalized or ocular MG showed abnormalities in the EFs, and 4 patients showed abnormalities in the ADP. A regional curare test was performed in the EFs of 11 patients with borderline or no abnormalities in the EFs and the ADP. All patients were more sensitive to curare than were control subjects; in 2, a decrement outside the range of controls could only be provoked in the partly curarized muscle during posttetanic exhaustion. Excitation-contraction coupling, as evidenced by the staircase phenomenon and after correction for blackade of fibers, was abnormal in 5 of 31 patients in the EFs, and in 11 patients in the ADP. In both muscles, the action potential was a more sensitive criterion of abnormality than the mechanical response. The decrement in the action potentials during 3/sec stimuli gave the largest diagnostic yield.

Action Potentials↗
PubMed1988

GABA activated chloride currents in cultured rat hippocampal and septal region neurons can be inhibited by curare and atropine.

In order to study the influence of curare and atropine on the gamma-aminobutyric acid (GABA)-evoked chloride current, we have investigated cultures of hippocampal and septal region neurons from embryonic rats (E18). The neurons were cultured under the trophic influence of spatially separated astrocytes in serum-free medium. By means of the patch clamp technique, the excitable cells displayed GABA induced chloride currents within 1-15 days in vitro. In both cultures picrotoxin or bicuculline as well as curare or atropine reversibly inhibited the chloride current in a dose dependent manner. We conclude that curare and atropine are not specifically anti-cholinergic for cultured central neurons. Our results provide evidence for common ligand binding properties shared by GABAA and acetylcholine (ACh) receptors supporting the recent concept of a receptor superfamily.

Animals↗