Abstract

Malignant hyperthemia, which can be initiated in susceptible humans and swine by the volatile anesthetic halothane, appears to result from abnormal responses in skeletal muscle. We have inferred the primary defect in susceptible muscles by observing their responses to certain drugs. Furthermore, we compared the responses of cut muscle cell preparations, such as those used in the diagnostic caffeine test, with those of intact muscle cells. Specifically, we investigated the effects of halothane, caffeine, succinylcholine and catecholamines on the mechanical properties of intact muscle cells from normal pigs, mice and frogs and susceptible pigs. The results from intact and paired cut cell preparations were qualitatively similar. Halothane (2%) caused a 30% decrease in peak tetanic tension in susceptible porcine muscle but less than a 10% change in other muscles. Halothane potentiated twitch tension in frog and susceptible pig muscle. The latter was 4 times more sensitive to caffeine twitch potentiation than normal muscle. Porcine intercostal muscles were more sensitive to caffeine than limb extensor muscles and the difference between normal and susceptible muscle was less with intercostal muscles. Succinylcholine and catecholamines had small and opposite effects on porcine muscles; when used together in combination with halothane there was little effect on normal muscle but a dramatic decrease in tetanic tension and rapid onset of contracture in susceptible muscle.