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Biomedical subjects

F F Foldes

Publications and source records attributed to F F Foldes.

At least 37 records · Page 2Linked to original sources
PubMed1988

Potentiation of neuromuscular blocking agents by calcium channel blockers in rats.

The effect of calcium channel blockers (Ca-antagonists) on the potency and reversibility of muscle relaxants (MR) was investigated in the in vitro phrenic nerve-hemidiaphragm and in vivo sciatic nerve-tibialis anterior preparation of rats. To increase the relevance of the experimental findings to the clinical situation, the [Ca++] and [Mg++] in vitro were the same as in the plasma of rats and humans and the stimulation parameters used in vitro and in vivo were similar to those that elicit voluntary movements of the muscles used. Both verapamil and nifedipine significantly decreased the I50 and I90 of d-tubocurarine (d-Tc), pancuronium, vecuronium, and atracurium in vitro and those of the first three MR in vivo (P less than 0.001). In vitro, the depression of the force of contraction of the diaphragm (P) caused by all the Ca-antagonist-MR combinations could be reversed only partially by washout, neostigmine, or 4-aminopyridine. In vivo, because of limitations imposed by their cardiovascular depressant effect, the muscles were exposed to lower concentrations of Ca-antagonists for shorter periods. Under these circumstances the decrease of P caused by all Ca-antagonist-MR combinations recovered spontaneously close to control levels. This study indicates that acute administration of verapamil during anesthesia may increase MR potency, but it is unlikely that spontaneous recovery or reversibility of the residual neuromuscular (NM) block at the end of anesthesia will be significantly affected. However, long-term administration of Ca-antagonists may make difficult the reversal of the residual NM block.

Anesthesia↗
PubMed1987

Modulation of stimulation-evoked release of newly formed acetylcholine from mouse hemidiaphragm preparation.

A radioisotope method has been developed for measuring the stimulation-evoked release of acetylcholine without the use of cholinesterase inhibitors from the mouse hemidiaphragm preparation which had been loaded with 3H-choline. Evidence has been obtained that 3H-choline was taken up by and released from both innervated and non-innervated mouse hemidiaphragm preparations. However, it was released in the form of 3H-acetylcholine in response to electrical field stimulation only from the innervated preparations. Long lasting (51 min) S1 stimulation of the preparations exhausted the radioactive acetylcholine stores to the extent that S2 did not evoke any release of 3H. These data suggest that when the labelled acetylcholine stores become exhausted, the labelled choline, still present in the tissue, cannot be released by electrical stimulation. Tetrodotoxin (1 mumol/l) administration and Ca withdrawal inhibited, 20-100 mumol/l 4-aminopyridine enhanced the release of 3H-acetylcholine in response to electrical stimulation. Activation of the presynaptic muscarinic receptors by the agonist oxotremorine (50 mumol/l) decreased the liberation of 3H-acetylcholine. The muscarinic antagonist atropine (1 mumol/l) abolished the inhibitory effect of oxotremorine and by itself increased the evoked release of the newly formed 3H-acetylcholine. Adenosine (50 mumol/l) reduced the evoked release of radioactivity. Theophylline (30 mumol/l) prevented the inhibitory effect of adenosine and itself enhanced the release. Xylazine (1 mumol/l), an alpha 2-adrenoceptor agonist did not affect the release. It is concluded that the stimulation-evoked release of 3H-acetylcholine from the mouse phrenic nerve hemidiaphragm preparation preloaded with 3H-choline is derived from the motor nerves. The release of acetylcholine is modulated by activation of presynaptic muscarinic and adenosine receptors.

4-Aminopyridine↗
PubMed1987

Effect of mono- and diaminopyridines on release of [3H]norepinephrine from isolated guinea-pig atrium.

Neurochemical evidence has been obtained that 4-aminopyridine, 3,4-diaminopyridine and 3,3-dimethyl-1-(4-amino-3-pyridyl)urea HBr (LF-14), concentration-dependently enhanced the stimulation-evoked release of [3H]norepinephrine ([3H]NE) from isolated guinea-pig atrium. The effects of aminopyridines, compounds known to inhibit potassium channels, were Ca0-dependent. High pressure liquid chromatography, combined with radiochemical detection, indicated that the increased stimulated release of radioactivity was due to [3H]NE. Since the aminopyridines studied also enhanced the release of [3H]NE from atrium treated with cocaine, a blocker of uptake1, it seems likely that the increased release of NE caused by the aminopyridines is due to the enhanced release of NE from sympathetic axon terminals and not to the inhibition of reuptake. It is probable that the sympathomimetic cardiac effects (positive inotropic and chronotropic effect) of aminopyridines observed in animal experiments is due to the increased release of NE, caused by these compounds.

4-Aminopyridine↗
PubMed1987

Direct evidence that pancuronium and gallamine enhance the release of norepinephrine from the atrial sympathetic nerve by inhibiting prejunctional muscarinic receptors.

The effect of different non-depolarizing muscle relaxants (gallamine, pancuronium, vecuronium, D-tubocurarine) on [3H]norepinephrine release in response to electrical stimulation was studied in isolated guinea-pig atrium. High pressure liquid chromatography combined with electrochemical and radiochemical detection revealed that the released radioactivity was mainly in the form of [3H]norepinephrine release. Oxotremorine, a pure muscarinic agonist, reduced the release of tritium. Gallamine and pancuronium, like atropine, prevented the inhibitory effect of oxotremorine. D-Tubocurarine and vecuronium had no such effect. These findings indicate that gallamine and pancuronium exert a presynaptic antimuscarinic, atropine-like effect, by inhibiting muscarinic receptors located on the axon terminals of sympathetic neurons thereby enhancing norepinephrine release. It is suggested that this phenomenon might play some role in tachycardia observed during surgical anaesthesia when gallamine or pancuronium have been administered.

Adrenergic Fibers↗
PubMed1985

A simple and sensitive method of acetylcholine identification and assay. Bioassay combined with minicolumn gel filtration or high-performance liquid chromatography.

A modified technique of acetylcholine assay on the guinea pig ileum has been combined with either minivolume gel filtration or high-performance liquid chromatography separation of the samples. In addition, labeled acetylcholine (14C-ACh) was eluted with unlabeled acetylcholine or with the samples expected to contain acetylcholine, and their elution profiles were compared by bioassay plus radioassay of eluate fractions. When the elution of both biological activity and label occurred in the same eluates, it was concluded that the substance assayed on guinea pig ileum was acetylcholine. The method was sensitive to 0.5 ng (1.8 pmol) of acetylcholine and its reproducibility was within 5%. It thus represents a substantial improvement in chemical specificity over the previous bioassay method described by Paton and Vizi (1969).

Acetylcholine↗
PubMed1985

Rapid tracheal intubation with vecuronium: the priming principle.

Following the administration of a single 0.1 mg/kg dose of vecuronium bromide, satisfactory conditions for tracheal intubation developed in 156 +/- 12 s (mean +/- SEM), and the clinical duration of the initial dose was 36 +/- 2 min. When the initial dose of vecuronium was administered in two increments, a 0.015 mg/kg "priming" dose, followed 6 min later by a 0.050 mg/kg "intubating" dose, intubation time decreased to 61 +/- 3 s and clinical duration to 21 +/- 1 min. The priming dose that had no unpleasant effect on premedicated, awake patients could be administered 3-4 min before, and the intubating dose 2 to 3 min after induction of anesthesia. With the described technique, comparable intubating conditions could be obtained just as rapidly with vecuronium as with succinylcholine chloride, without subjecting the patients to the side effects of and the complications occasionally encountered with succinylcholine. An added advantage of the use of a priming dose is that it will reveal undiagnosed, pathologic, or idiopathic increase of sensitivity to nondepolarizing muscle relaxants.

Adolescent↗
PubMed1985

The effect of verapamil and EGTA on the rat phrenic nerve-hemidiaphragm preparation.

Relatively high concentrations of verapamil or EGTA [ethylene glycol-bis (beta-aminoethyl ether) N, N, N',N'-tetra acetic acid] inhibit contraction (P) of the rat phrenic nerve-hemidiaphragm preparation elicited by direct or indirect stimulation. The inhibitory effect of verapamil is greater (P less than 0.002) with direct (I50 = 26.3 +/- 1.7 microM) than indirect = I50 = 37.6 +/- 1.9 microM) stimulation. For EGTA the reverse is true: I50 is 1320 +/- 80 microM with direct and 1100 +/- 60 microM with indirect stimulation. The greater than 90% verapamil-induced depression of P can only be partially reversed by washout. Increasing the [Ca2+] or the addition of 4-aminopyridine (4AP) has insignificant antagonist effect. Except for the antagonism by 4AP during direct stimulation, the EGTA-induced depression of P is better antagonized by washout, increase of the [Ca2+], or the addition of 4AP than that caused by verapamil. Neostigmine did not antagonize the depression of P caused by either verapamil or EGTA. The findings presented indicate that the primary site of action of verapamil is postjunctional and that of EGTA is prejunctional.

4-Aminopyridine↗
PubMed1985

Verapamil is not a therapeutic adjunct to dantrolene in porcine malignant hyperthermia.

We have investigated the hypothesis that the calcium antagonist verapamil might be useful for prevention or treatment of malignant hyperthermia (MH) in MH-susceptible (MHS) swine. MH episodes were triggered in four groups of four swine with halothane alone or combined with succinylcholine (SCh) and, with and without verapamil. MH episodes were reversed by therapy with dantrolene and NaHCO3 in all groups. Verapamil did not alter MH episodes triggered by halothane alone or combined with SCh. The dantrolene-NaHCO3 requirements for reversal of MH were greater for the groups receiving halothane-SCh, but did not differ in groups pretreated with and without verapamil. In vitro verapamil (25 microM) did not reduce responses of intact muscle fibers to halothane and, in fact, exaggerated some halothane-induced responses. High concentrations of verapamil (0.5 mM) caused contractures in MHS but not in normal muscles. Neither our in vivo nor in vitro results support the use of verapamil in the treatment of MH. Further, doses of dantrolene used to reverse these MH episodes, although admittedly small (1-2 mg/kg), did not produce myocardial depression when used in combination with verapamil.

Anesthesia, Inhalation↗
PubMed1984

Neuromuscular blocking action of two brevetoxins from the Florida red tide organism Ptychodiscus brevis.

The action of Ptychodiscus brevis "brevetoxins" T17 and T34 on rat phrenic nerve-stimulated hemidiaphragm contraction is reported. The potency of T34 is greater than the potency of T17, but both cause a complete block of neuromuscular transmission in the nM to pM concentration ranges. Preparations exposed to low concentrations of T17 can recover in the presence of the toxin, whereas the effects of T34 are irreversible. The initial contracture produced by each is prevented by tetrodotoxin or curare. Neuromuscular block does not appear to be due to acetylcholine depletion, as determined by electron microscope examination of the neuromuscular junctions of blocked preparations. Persistent nerve depolarization is believed to be responsible for the neuromuscular block.

Animals↗
PubMed1984

Myoneural effects of pethidine and droperidol.

In vitro experiments on the rat phrenic nerve-hemidiaphragm preparation, stimulated directly or indirectly with supramaximal impulses at 0.1 Hz revealed that pethidine in concentrations greater than 5 micrograms ml-1 caused a rapid increase of the twitch. This was maximal (60% increase during direct and 70% increase during indirect stimulation) with pethidine 75 micrograms ml-1. With concentrations of pethidine greater than 40 micrograms ml-1, the initial increase was followed by a slowly developing inhibition of the twitch (50% depression with 46.0 and 50.4 micrograms ml-1 during direct and indirect stimulation, respectively). Droperidol caused no increase in twitch, but it depressed the twitch by 50% at concentrations of 9.8 and 6.9 micrograms ml-1 during direct and indirect stimulation, respectively. The increase in twitch produced by pethidine was augmented by 4-aminopyridine and inhibited by verapamil during both direct and indirect stimulation. Tubocurarine antagonized the augmentation of the twitch by pethidine only during indirect stimulation. The pethidine- and droperidol-induced inhibition of the twitch could be reversed by washout, but it was not antagonized by neostigmine or 4-aminopyridine. The inhibitory effect of pethidine and droperidol were additive. Sub-effective inhibitory concentrations of pethidine and droperidol, and those of tubocurarine, pancuronium and suxamethonium, independently of the sequence of their administration, mutually increased the myoneural effects of one another. The resulting twitch depression could be reversed by washout. The inhibition caused by the combination of pethidine with tubocurarine or pancuronium was partially antagonized by neostigmine or 4-aminopyridine.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1983

Protein binding of atracurium and other short-acting neuromuscular blocking agents and their interaction with human cholinesterases.

The interaction of three new non-depolarizing neuromuscular blocking agents--atracurium, vecuronium and Duador--on human red cell acetylcholinesterase (AChE; EC 3.1.1.7) and human plasma butyrylcholinesterase (BuChE; EC 3.1.1.8) was investigated. The binding of these neuromuscular blockers to human plasma proteins (protein binding) was also studied with a new method not requiring dialysis. For sake of comparison the protein binding and the interaction of tubocurarine and pancuronium with AChE and BuChE were observed also. None of the drugs studied was a substrate of AChE or BuChE. All had a relatively weak inhibitory effect on AChE (I50 greater than 10(-5) mol litre-1 in assay systems containing 5% haemolysed red cells). Of the three new neuromuscular blockers, vecuronium and Duador were relatively potent inhibitors of BuChE (I50 less than 10(-5) mol litre-1 in assay systems containing 5% plasma), but less potent than pancuronium (I50 = 6.1 X 10(-8) mol litre-1). All neuromuscular blocking drugs tested, especially vecuronium and pancuronium, were strongly (77-91%) bound to plasma proteins.

Acetylcholinesterase↗
PubMed1983

Muscular relaxation with atracurium, vecuronium and duador under balanced anaesthesia.

The neuromuscular effects of three new nondepolarizing neuromuscular blocking drugs, atracurium, vecuronium and Duador, were investigated in surgical patients under balanced anaesthesia. (The numbers of patients in each study are given in the tables.) There were no significant differences in the neuromuscular effects of the three agents. None showed any cumulation after repeated administration of maintenance doses. Muscular relaxation for upper abdominal surgery was adequate as long as the isometric twitch tension (P) was no more than 25% of control. Conditions for tracheal intubation were satisfactory within less than 3 min after the start of injection. Spontaneous recovery of P to 90-95% of control, after the last dose of neuromuscular blocker was the fastest with vecuronium (35.8 +/- 2.4 min) and about the same with atracurium (54.3 +/- 2.4 min) and Duador (54.2 +/- 4.7 min). The T4/T1 ratio at the time of greater than 90% recovery of P was 0.44, 0.52 and 0.56 with vecuronium, Duador and atracurium, respectively, indicating the need for the reversal of the residual neuromuscular block. This could be accomplished within 2 min by the i.v. injection of edrophonium 0.5 mg kg-1, preceded by atropine 0.01 mg kg-1. No side-effects were observed with vecuronium. Atracurium caused mild to moderate histamine release in four of 50 patients included in this study, all of whom received an initial dose of 0.5 mg kg-1. The initial dose of Duador caused a 16.7% increase in heart rate. The findings indicate that the three new muscle relaxants merit further clinical trial. In our opinion, until the results of such studies become available, atracurium should not be used in patients with a history of allergic diathesis and Duador in those in whom increased heart rate may be harmful.

Androstanes↗