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In patients with malignant hyperthermia, a variety of agents, especially, the widely used general anesthetic halothane, will produce a dramatic rise in body temperature, metabolic and respiratory acidosis, hyperkalemia, and muscle rigidity. This genetic abnormality occurs in about 1 in 15,000 children and 1 in 50,000-100,000 older peoples. It is dominantly inherited. Death may result the first time a susceptible person is anesthetized. Onset occurs within minutes of medicine exposure and the hyperthermia must be recognized immediately. Packing the patient in ice is effective and should be accompanied by measures to combat acidosis. The medicine dantrolene is also effective.

A phenomenon similar, if not identical, to malignant hyperthermia is known to occur in pigs. Pigs with this problem, called porcine stress syndrome, respond poorly to stress. This genetic disease usually manifests itself as the pig is being shipped to market. Pigs with the syndrome can be identified by exposure to halothane, which triggers the same response seen in patients with malignant hyperthermia. The meat of pigs that have died as a result of the syndrome is pale, watery, and of very low pH that is nearly pickled.

Muscle is the site of the primary lesion in both malignant hyperthermia and porcine stress syndrome. In response to halothane the skeletal muscles become rigid and generate heat and lactic acid. The sarcoplasmic reticulum of such pigs and patients has a genetic abnormality in the ryanodine receptor, a calcium release channel that plays an important function in excitation-contraction coupling in muscle. Because of a defect in this protein, the anesthetic triggers in appropriate release of calcium from the sarcoplasmic reticulum. This results in uncontrolled stimulation of a number of heat-producing process, including myosin ATPase, glycogenolysis, glycolysis, and cyclic uptake and release of calcium by mitochondria and sarcoplasmic reticulum.

Muscle cells become irreversibly damaged as a consequence of excessive heat production, lactic acidosis, and ATP loss.