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British Journal of Anaesthesia Sep 1981
Topics: Humans; Neostigmine; Neuromuscular Junction; Tubocurarine
PubMed: 7284216
DOI: 10.1093/bja/53.9.1006-a -
British Journal of Anaesthesia May 1981The effect of disopyramide on neuromuscular transmission has been studied using the rat isolated phrenic nerve-diaphragm preparation. The response of the muscle to...
The effect of disopyramide on neuromuscular transmission has been studied using the rat isolated phrenic nerve-diaphragm preparation. The response of the muscle to indirect nerve stimulation was decreased in the presence of disopyramide 5.6 x 10(-6) mol litre-1 (P less than 0.05), total blockade occurring at 5.6 x 10(-4) mol litre-1. Marked augmentation of the response to direct muscle stimulation was recorded in the presence of disopyramide 1.8 x 10(-4)-5.6 x 10(-4) mol litre-1. Disopyramide 5.6 x 10(-6) mol litre-1 caused a leftward shift of the log concentration response for tubocurarine and decreased the antagonist effect of neostigmine.
Topics: Animals; Disopyramide; Dose-Response Relationship, Drug; Drug Synergism; In Vitro Techniques; Neostigmine; Neuromuscular Junction; Pyridines; Rats; Synaptic Transmission; Tubocurarine
PubMed: 6263303
DOI: 10.1093/bja/53.5.495 -
The Journal of Physiology Jan 19731. Neuromuscular transmission in the presence and absence of D-tubocurarine was examined in cut muscle preparations of the rat diaphragm using intracellular recording...
1. Neuromuscular transmission in the presence and absence of D-tubocurarine was examined in cut muscle preparations of the rat diaphragm using intracellular recording techniques. The method of localizing the end-plates is described and evidence is presented indicating that end-plate potential (e.p.p.) recordings were made close to the end-plate region and that reliable estimates of the quantum content of e.p.p.s could be made.2. During repetitive nerve stimulation at rates between 2 and 10 Hz, e.p.p. amplitudes declined in response to the first 6-8 stimuli to reach a plateau level which was maintained for 1500 stimuli. At higher rates of stimulation some 500-700 stimuli were needed before a plateau level of amplitude was reached. It was demonstrated that these amplitude changes reflected similar changes in the quantal release of ACh.3. Tubocurarine in a concentration of 4 x 10(-8) g/ml. had no effect on quantal release but did reduce quantal size. In the presence of tubocurarine, 8 x 10(-8) g/ml., small reductions in the quantum content of the first e.p.p. in response to a train of stimuli and the maintained quantal release were observed. In the presence of tubocurarine 4 x 10(-7) g/ml., the quantum content of the first e.p.p. and the maintained release were further reduced, to the level previously described for curarized preparations. At this concentration a significant effect of tubocurarine upon the presynaptic measurements could be detected (t test). Studies on single junctions revealed that the post- and presynaptic effects of tubocurarine developed with different time courses.4. Neuromuscular preparations in vivo have been reported to be much more resistant to maintatined stimulation than curarized neuromuscular preparations in vitro. It is suggested that this disparity is explained by the presynaptic action of tubocurarine.5. From the quantal release rates of the present investigation and reports of ACh release/stimulus/end-plate in previous investigations it can be calculated that a quantum of ACh contains between 12,000 and 21,000 molecules.
Topics: Acetylcholine; Action Potentials; Animals; Calcium; Diaphragm; Electric Stimulation; Electrophysiology; In Vitro Techniques; Microelectrodes; Muscles; Neuromuscular Junction; Rats; Synaptic Transmission; Time Factors; Tubocurarine
PubMed: 4346989
DOI: 10.1113/jphysiol.1973.sp010088 -
Anesthesiology Aug 1995Increases in acetylcholine receptors (AChRs) at the muscle membrane, induced by burn injury, have been associated with a hyperkalemic response to succinylcholine and...
BACKGROUND
Increases in acetylcholine receptors (AChRs) at the muscle membrane, induced by burn injury, have been associated with a hyperkalemic response to succinylcholine and resistance to d-tubocurarine-like drugs. Muscle relaxants often are administered to burn-injured patients in the intensive care unit to facilitate mechanical ventilation. This study in rats tested whether continuous administration of d-tubocurarine in subparalytic doses exaggerates the upregulation of AChRs induced by burn trauma. Subparalytic doses were used to avoid the confounding effects of immobilization.
METHODS
Three days after an approximate 50% body surface area burn or sham injury, the animals received an infusion of 3.03 +/- 0.05 micrograms/h of d-tubocurarine or equal volume of saline directly to the left gastrocnemius muscle via catheter connected to a subcutaneously implanted osmotic pump. After 7 days of d-tubocurarine or saline infusion, the AChRs were quantitated using 125I-alpha-bungarotoxin. The AChRs on the d-tubocurarine or saline-infused left gastrocnemius were compared to the contralateral gastrocnemius in the same group. The right or left gastrocnemius AChRs were compared to the ipsilateral muscles between groups. These intra- and intergroup comparisons allowed the delineation of the effects of catheter irritation, burns, or d-tubocurarine on AChRs.
RESULTS
Daily examination of the withdrawal response to toe-pinch revealed no evidence of paralysis. Weight loss in the burn-injury animals receiving d-tubocurarine or saline was similar, confirming that the infusion of d-tubocurarine did not impair the mobility of the animals to move and feed. The plasma d-tubocurarine concentration after 7 days of infusion was 26.0 +/- 12 ng/ml (mean +/- SE). Regardless of burn or sham injury or of d-tubocurarine or saline infusion, the concentration of AChRs on the left was consistently greater than in the contralateral right gastrocnemius muscles within the same group, indicating that manipulation of the area alone can result in upregulation of AChRs. The AChRs in the right gastrocnemius of burn-injured animals were greater than those in the same muscle of sham-injured animals, regardless of saline (7.24 +/- 0.9 vs. 5.7 +/- 0.5 fmoles/mg protein, P = 0.06) or d-tubocurarine (7.3 +/- 0.4 vs. 5.7 +/- 0.5, P < 0.05) infusion to the burn-injury groups. AChRs in the left gastrocnemius of burn-injury animals receiving d-tubocurarine were significantly greater than those in burn- or sham-injury animals receiving saline (13.9 +/- 1.1 vs. 9.8 +/- 1.2 and 7.1 +/- 0.5 fmoles/mg protein, respectively, P < 0.05).
CONCLUSIONS
Burn-induced upregulation of AChRs is accentuated by infusion of subparalytic doses of d-tubocurarine. Concomitant administration of d-tubocurarine to burn-injured patients may result in further exaggeration of the aberrant responses to neuromuscular relaxants.
Topics: Animals; Body Weight; Burns; Male; Muscles; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic; Tubocurarine
PubMed: 7631953
DOI: 10.1097/00000542-199508000-00011 -
The Journal of Physiology Feb 1951
Topics: Animals; Bis-Trimethylammonium Compounds; Cats; Cell Respiration; Decamethonium Compounds; Muscles; Respiration; Tubocurarine
PubMed: 14825214
DOI: 10.1113/jphysiol.1951.sp004531 -
Anesthesiology 1967
Topics: Animals; Bile; Dogs; Injections, Intravenous; Kidney; Kidney Function Tests; Liver; Tubocurarine
PubMed: 6026049
DOI: 10.1097/00000542-196703000-00004 -
Anesthesiology Jul 1974
Topics: Anesthetics; Animals; Diaphragm; Drug Synergism; Electric Stimulation; Ethers; Halothane; Hydrocarbons, Fluorinated; Muscle Contraction; Neuromuscular Junction; Phrenic Nerve; Succinylcholine; Tubocurarine
PubMed: 4834378
DOI: 10.1097/00000542-197407000-00011 -
British Journal of Pharmacology Apr 19731. In anaesthetized patients under controlled respiration, samples of lumbar cerebrospinal fluid were withdrawn 15 and 60 min after an intravenous injection of 30 mg...
1. In anaesthetized patients under controlled respiration, samples of lumbar cerebrospinal fluid were withdrawn 15 and 60 min after an intravenous injection of 30 mg tubocurarine. When tested on the frog rectus muscle preparation contracted by acetylcholine, they exerted curare-like activity which corresponded to between 0.05 and 0.33 mug/ml tubocurarine.2. In dogs anaesthetized with pentobarbitone sodium and artificially ventilated, two procedures were adopted to find out if tubocurarine passes into the liquor space after an intravenous injection of 0.3 or 3 mg/kg and during its intravenous infusion at a rate of 10 (mug/kg)/minute. Either samples of cisternal cerebrospinal fluid (c.s.f.) were collected, or different regions of the liquor space were perfused with artificial c.s.f. and the effluent was collected. The samples of c.s.f. and the effluent were assayed for curare-like activity on the frog rectus muscle.3. After the intravenous injection of tubocurarine samples of cisternal effluent collected during perfusion from lateral ventricle to cisterna exerted curare-like activity. It corresponded to 20 ng/min tubocurarine in the sample collected during the first 15 min after the injection of 0.3 mg/kg and to 40-60 ng/min in the samples collected up to 2 h after the injection of 3 mg/kg.4. During intravenous infusion of tubocurarine the cisternal c.s.f. as well as the effluent from the perfused regions of the liquor space exhibited curare-like activity. Expressed in equivalents of tubocurarine, the activity in the cisternal c.s.f. ranged from between 0.1 and 0.75 mug/ml. On perfusion from lateral ventricle to aqueduct or cisterna, the activity ranged from between 3 and 25 ng/min in the aqueductal and from between 4 and 40 ng/min in the cisternal effluent. On perfusion from the lumbar-spinal subarachnoid space to cisterna it ranged from between 6 and 55 ng/min in the cisternal effluent.
Topics: Acetylcholine; Animals; Atropine; Blood Pressure; Cerebral Aqueduct; Cerebral Ventricles; Cisterna Magna; Dogs; Humans; Injections, Intravenous; Muscle Contraction; Perfusion; Respiration; Subarachnoid Space; Time Factors; Tubocurarine
PubMed: 4723800
DOI: 10.1111/j.1476-5381.1973.tb08206.x -
Anesthesiology Oct 1986Administration of d-tubocurarine (dTC) or diphenylhydantoin (DPH) was evaluated as a pretreatment to prevent succinylcholine (Sch) evoked fasciculations. Experiments...
Administration of d-tubocurarine (dTC) or diphenylhydantoin (DPH) was evaluated as a pretreatment to prevent succinylcholine (Sch) evoked fasciculations. Experiments were designed to determine the nature of the drug-drug interactions, sites of interaction, and site of fasciculation suppression. Sch is known to evoke repetitive discharge generation by motor nerve terminals (MNTs). Transmission of these prejunctional discharges causes fasciculations. A cat soleus neuromuscular preparation in situ, which enables recording of nerve action potentials initiated by MNTs, their transmitted muscle action potentials, and the resultant contractile responses, was used to explore Sch effects before and after iv pretreatment with dTC or DPH. dTC is known to act prejunctionally to suppress repetitive discharges initiated by facilitatory drugs and tetanic conditioning of MNTs. Accordingly, pretreatment with dTC 50 micrograms X kg-1 suppressed the Sch-induced MNT repetitive discharging and correspondingly suppressed generalized fasciculations without affecting twitch. This dTC dose, however, also reduced Sch blocking potency by 33%, slowed its rate, and shortened block duration. These latter effects represent competitive postjunctional antagonism. DPH is also known to suppress MNT repetitive discharging. Correspondingly, Sch-induced repetitive firing and ensuing fasciculations were suppressed by DPH (30 mg X kg-1) without affecting twitch. Unlike dTC, this DPH dose increased Sch blocking potency by 50%, increased the initial rate of block, and did not alter block duration. These DPH effects were dose-dependent and within the anticonvulsant range for cats. Therefore, patients with anticonvulsant levels of DPH may not require pretreatment before Sch.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Axons; Cats; Drug Interactions; Electrophysiology; Evoked Potentials; Female; Male; Muscle Contraction; Phenytoin; Succinylcholine; Time Factors; Tubocurarine
PubMed: 3767039
DOI: 10.1097/00000542-198610000-00010 -
Epilepsia May 1997In rodents, specific motor components of generalized convulsive seizures depend on two distinct anatomic substrates: (a) forebrain networks are responsible for facial...
PURPOSE
In rodents, specific motor components of generalized convulsive seizures depend on two distinct anatomic substrates: (a) forebrain networks are responsible for facial and forelimb clonus with or without rearing and falling; and (b) brainstem networks are responsible for running-bouncing fits and tonic convulsions. To investigate the requirement of proprioceptive inputs in the generation of these two different types of seizures, we compared the effects of neuromuscular blockade by D-tubocurarine on the EEG expression of brainstem- and forebrain-triggered seizures.
METHODS
Unilateral electrical stimulations were applied for 50 consecutive days in freely moving male adult rats through a bipolar electrode aimed at the dorsal hippocampus (n = 5), the occipital cortex (n = 4), the inferior colliculus (n = 6), or the midbrain reticular formation (n = 6). Two days after the last stimulation, rats were paralyzed with d-tubocurarine and stimulated in the same way.
RESULTS
In brainstem structures, the first electrical stimulation induced tonic seizures concomitant with low-voltage cortical activity; repetition of daily stimulations progressively induced tonic-clonic seizures associated with high-amplitude cortical spike-wave discharges. After immobilization by d-tubocurarine, brainstem stimulations failed to induce any EEG paroxysm. In forebrain structures, repeated electrical stimulations produced a classic kindling with progressive occurrence of clonic seizures associated with large cortical discharges; d-tubocurarine left unchanged the EEG pattern of these latter seizures.
CONCLUSIONS
These data suggest that proprioceptive reafferentation resulting from movement is necessary for the generation of self-sustained brainstem seizures but is not implicated in the elaboration of forebrain seizures.
Topics: Animals; Brain Stem; Electric Stimulation; Electroencephalography; Feedback; Immobilization; Kindling, Neurologic; Male; Motor Activity; Proprioception; Prosencephalon; Rats; Seizures; Tubocurarine
PubMed: 9184594
DOI: 10.1111/j.1528-1157.1997.tb01133.x