Canadian Anaesthetists’ Society Journal

, Volume 31, Issue 2, pp 130–154

Dantrolene -In vitro studies in malignant hyperthermia susceptible (MHS) and normal skeletal muscle

  • Beverley A. Britt
  • Elizabeth Scott
  • Wanda Frodis
  • Mary-Jean Clements
  • Laszlo Endrenyi
Article
  • 247 Downloads

Abstract

Dantrolene sodium, a hydantoin analogue, is efficacious in the therapy of malignant hyperthermia (MH). In order to improve our knowledge of the mode of action of dantrolene, we have examined the influence of dantrolene sodium on; (1) twitch and resting tensions, in the absence and the presence of caffeine, of intact skeletal muscle fascicles; and (2) caffeine induced tension rises of single chemically skinned skeletal muscle fascicles.

We have found that dantrolene appears to exert its beneficial action on malignant hyperthermia susceptible (MHS) skeletal muscle by an indirect action on the sarcoplasmic reticulum (SR). Thus dantrolene inhibits twitch tensions of skeletal muscle fascicles, probably by indirectly preventing the release of calcium from the SR. To a lesser extent dantrolene inhibits caffeine induced contractures of skeletal muscle fascicles, probably by indirectly accelerating the uptake of calcium into the SR. Because the former effect is greater than the latter in vivo dantrolene sodium is effective only when given prior to total loss of calcium from the SR. Vigilant temperature and EKG monitoring of all patients during anaesthesia is, therefore, essential.

Key words

hyperthermia malignant dantrolene muscle skeletal caffeine twitch tension contracture resting tension 

Résumé

Le dantrolène sodique, un analogue de l’hydantoin, est efficace dans le traitement de VHyperthermie maligne. Pour améliorer notre connaissance du mode d’action du dantrolène, nous avons étudié l’influence du dantrolène sodique sur: 1) la tension de contraction et de repos avec ou sans caféine sur des faisceaux de muscle squelettique intacts; et 2) l’augmentation de la tension induite par la caféine sur des faisceaux de muscle squelettique enrobés chimiquements. Nous avons trouvé que le dantrolène semble exercer son action bénéfique sur le muscle squelettique susceptible à l’Hyperthermie maligne par une action indirecte sur le réticulum sarcoplasmique (RS). Le dantrolène inhibe les tensions de contraction des faisceaux de muscle squelettique, probablement en prévenant indirectement le largage du calcium du RS. A un moindre degré, le dantrolène inhibe les contractures des faisceaux du muscle squelettique induites par la caféine probablement en accélérant indirectement la captation du calcium dans le RS.

Parce que le premier effet est plus important que le deuxième in-vivo, le dantrolène est efficace uniquement lorsqu’il est administré avant le largage total du calcium par le RS, Une surveillance vigilante de la température et de V électrocardiogramme pendant l’anesthésie est essentielle.

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Copyright information

© Canadian Anaesthesiologists 1984

Authors and Affiliations

  • Beverley A. Britt
    • 1
    • 2
  • Elizabeth Scott
    • 1
  • Wanda Frodis
    • 1
  • Mary-Jean Clements
    • 1
  • Laszlo Endrenyi
    • 1
  1. 1.Departments of Anaesthesia and PharmacologyPreventative Medicine and Biostatistics, University of TorontoToronto
  2. 2.Dept. of AnaesthesiaUniversity of TorontoToronto

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