Malignant hyperthermia: responses of skeletal muscles to general anesthetics

Anesthetic-induced malignant hyperthermia (MH) originally attracted scientific interest because of the associated high fatality rate. Recently, the introduction of treatment with the muscle relaxant dantrolene sodium has dramatically reduced the frequency of death from MH. Nonetheless, diagnosing MH susceptibility remains a problem because it necessitates a muscle biopsy specimen that must be tested in a specially equipped laboratory. Thus, diagnosis is both expensive and invasive. Development of simpler and less invasive methods would be aided by identification of the primary defect underlying initiation of MH. Our understanding of whole-body responses during MH episodes and the development of treatment with dantrolene sodium have both resulted from studies of porcine MH, which is similar to the syndrome in humans. Investigations of porcine MH have demonstrated that the defect responsible for initiation of MH must be located in skeletal muscle. Many abnormal responses of MH muscle have been identified after exposure to triggering agents. These defects contribute to the maintenance and amplification of the MH episode once it has been initiated. The primary defect responsible for triggering this complex chain of events, however, has thus far eluded definition.