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

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 mumol/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 mumol/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.