STUDIES ON NORMAL HUMAN SKELETAL MUSCLE IN RELATION TO THE PATHOPHARMACOLOGY OF MALIGNANT HYPERPYREXIA

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Abstract
SUMMARY: 1. The effects of dantrolene on pharmacologically‐induced contractures and potentiated isometric twitches in normal human skeletal muscle have been studied in vitro.2. Dantrolene sodium, at concentrations of 3 μmol/l or less, attenuates basal twitch, inhibits halothane potentiation of basal twitch and inhibits halothane‐potentiated potassium contractures, but has less effect on twitch potentiation by 2 mmol/l caffeine.3. Caffeine contractures are attenuated by dantrolene concentrations of 12 μmol/l or greater. The effect of dantrolene on caffeine contracture is characterized by decreased contracture tension and by prolonged time to peak contracture.4. The results indicate that halothane and 2 mmol/l caffeine have agonistic effects on the excitation‐contraction (E‐C) coupling mechanism, and suggest that they may act at separate E‐C coupling sites. The relationships of these findings to the pathopharmacology of malignant hyperpyrexia are discussed.

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