Malignant hyperthermia: biochemical aspects of the acute episode.

Early studies indicated that the pharmacogenetic disorder, malignant hyperthermia (MH), was inherited as an autosomally dominant trait in humans [3]. More recent interpretations indicate that MH may be inherited through more than a single gene [9, 10] and that the pattern of inheritance may vary from recessive to dominant. This uncertainty about the mode of inheritance of human MH has contributed to the confusion which abounds in biochemical studies of the molecular aetiology of the syndrome. It now seems unlikely that MH is caused by a single enzyme or protein lesion such as is seen, for instance, in McArdle's disease or phenylketonuria. While the nature of the genetic abnormality remains unclear, there is good evidence that the fundamental defect is located in the fibres of the skeletal musculature. For example: tubocurarine will not block induction of MH by halothane; muscular rigidity is one of the first signs of onset of an MH episode; the neuromuscular blocker dantrolene blocks development of the syndrome and halothane-induced contractures of biopsy strips of muscle from MH