Cell Calcium in Malignant Hyperthermia

Abstract

Malignant hyperthermia (MH) is a genetic disease of man and various animal species that predisposes to a hypermetabolic syndrome triggered by certain anesthetic agents (Gronert, 1965; Nelson and Flewellen, 1983). Susceptibility to the MH syndrome is prevalent in swine and this also predisposes to a stress-induced syndrome in this species (Nelson, 1973). Potent volatile anesthetics such as halothane and depolarizing skeletal muscle relaxants such as succinylcholine are triggering agents for MH in susceptible man and animals. The state of anesthesia alone is not responsible for MH as evidenced by the fact that barbiturates, nitrous oxide, and narcotics can be used to provide anesthesia for the MH patient without triggering the syndrome. The primary defect for MH appears to be in skeletal muscle and a working hypothesis is that anesthetic agents which cause MH do so by producing a sustained increase in Ca²⁺ inside the muscle cell. Increases in myoplasmic Ca²⁺ below contracture threshold can increase oxygen consumption (Bianchiet al., 1975), and if unabated this can deplete energy necessary to maintain Ca²⁺ below contracture threshold. Further increases in myoplasmic Ca²⁺ can then activate the contractile elements, producing the clinical features of skeletal muscle rigidity and lactic acidosis that are observed in the malignant phases of the syndrome.