A Comparison of the Responses of the Tenuissimus Muscle to Neuromuscular Blocking Drugs in Vivo and in Vitro

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I Tritium-labelled decamethonium was infused intravenously in 12 cats at final rates of 1.3-4.2 nmol kg-' min-' to produce a steady plasma concentration which ranged between 0.21-1.3 gimol/l in different experiments. Muscle contractions were elicited by nerve stimulation and the potential at the end-plate regions of superficial fibres was recorded by extracellular electrodes. 2 Under these conditions, it was not possible to obtain a steady degree of neuromuscular block. The initial decrease in muscle contractions was followed by recovery towards the original value although the concentration of decamethonium in the plasma remained constant, or in some cases rose. The initial depolarization of the end-plate region also waned during the constant infusion of the drug. 3 Once the twitch tension had returned to control values during infusion of the drug, prolongation of the infusion for a total of four hours did not produce a secondary neuromuscular block. 4 Scintillation counting showed that during infusion oflabelled decamethonium the radioactivity ofthe muscles increased progressively with time. The uptake was less in the soleus muscle than in the fastcontracting flexor longus digitorum and extensor longus digitorum muscles. Muscles which had been denervated 12-13 days previously showed a greater uptake of labelled drug than control muscles from the contralateral limb. 5The labelled drug was localized by autoradiography of frozen sections of leg muscles following intra-arterial injection of decamethonium. Grain counts in individual fibres showed that small amounts of decamethonium had entered the muscle fibres along their entire length, and there was increased uptake of the drug into the cell in the region of the end-plate. 6 The mechanisms underlying the waning of the pharmacological response during constant application of depolarizing drugs are discussed.

Section: Discussionmentioning

confidence: 54%

Labelled Decamethonium in Cat Muscle

Creese

Maclagan

1976

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“…Desensitization in solution supplemented with constituents of tissue-culture media Since there is some indirect evidence to suggest that desensitization is more rapid in vitro than in vivo (Zaimis, 1959(Zaimis, , 1962Maclagan, 1962), it could be argued that this is because the bathing solutions normally used with isolated muscles lacked an important factor present in the living animal. It is, of course, well known that isolated cells survive for long periods only if they are kept in the supplemented media used in tissue culture, and it was thought possible that some of the factors included in such media might influence desensitization.…”

Section: Resultsmentioning

confidence: 99%

Influence of Skf‐525a Congeners, Strophanthidin and Tissue‐culture Media on Desensitization in Frog Skeletal Muscle

Terrar

1974

1Microelectrodes have been used to follow changes in membrane potential at end-plate regions of frog skeletal muscle fibres exposed to carbachol; the depolarizing drug was applied to narrow strips of muscle in a rapidly flowing solution containing relatively impermeant anions rather than chloride. 2 During prolonged applications of carbachol (10 to 20 gM), the depolarization caused by the drug showed a gradual decline which was attributed to desensitization. 3 Desensitization was little if at all affected by supplementing the exterulal solution with factors present in tissue-culture media, or by treating the muscle with strophanthidin (25 ,M). 4 The rate of repolarization in the presence of carbachol (10 to 20 gM) was greatly increased by the SKF-525A congeners pipenzolate bromide (10,Mm) and adiphenine hydrochloride (1 ,M). The desensitization-enhancing action of these compounds is discussed.

“…This loss of distinguishing characteristics is probably related to the changes in ion permeability which occur in isolated tissues (Creese & Northover, 1961;Krnjevic & Miledi, 1958), and also to the way in which the drug reaches the receptor sites (Gibberd, 1966). The most obvious characteristic common to all isolated nerve-muscle preparations is the biphasic response of the muscle to the continuing presence of the blocking agent (Jenden, Kamijo & Taylor, 1954;Jenden, 1955;Sabawala & Dillon, 1959;Maclagan, 1962;Taylor, 1962;Whittaker, 1962a, Freeman, 1968a. This response in particular has led to many of the current theories of the mechanism of depolarizing blockade in isolated nerve-muscle preparations.…”

Section: Discussionmentioning

confidence: 99%

The effect of some foreign anions on suxamethonium blockade of the isolated rat diaphragm preparation

Harris

Leach

1970

Summary1. The pharmacology of suxamethonium blockade of the rat phrenic nervediaphragm preparation has been studied in the presence of some foreign anions. 2. Blockade proceeded in two distinct phases in both normal and modified Krebs solution.3. In normal Krebs solution the characteristics bore no close resemblance to either depolarizing or competitive type blockade. 4. In the presence of foreign anions the characteristics of the blockade more closely resembled those of depolarization. 5. There was an increase in the sensitivity of the motor end-plate region of the muscle to the depolarizing action of acetylcholine, carbachol and suxamethonium in the presence of the anions. 6. Although the anions enhanced the depolarizing activity of suxamethonium, the blocking potency of the drug was unaltered. 7. It is suggested that end-plate depolarization plays little part in suxamethonium blockade of the isolated rat diaphragm and that desensitization is the primary cause of the blockade.