Malignant hyperthermia: aetiology unknown.

TLDR: Clinical and experimental evidence available to date indicate that the site of the defect is peripheral and not central, and changes in carbohydrate metabolism as indicated by lactic acid accumulation are prominent in pigs and presumably in man.

Abstract: The aetiology of malignant hyperthermia still remains obscure, but the search is narrowing. Clinical and experimental evidence available to date indicate that the site of the defect is peripheral and not central. Absence of muscle phosphorylase, impaired atpase activity of cell membranes, and the defect in myotonia dystrophica do not appear to be causative factors, at least not in those cases associated with rigidity. Metabolic defects in man known to be associated with mitochondrial alterations and an uncoupling of oxidative phosphorylation cause clinical symptoms which are not observed among patients predisposed to malignant hyperthermia. However, a combination of halothane and dinitrophenol in dogs has produced a syndrome with many features of malignant hyperthermia. The malignant hyperthermia which occurs on the basis of a genetic defect in Landrace pigs is not only clinically identical with the human syndrome, but also identical in many of the biochemical features. Changes in carbohydrate metabolism as indicated by lactic acid accumulation are prominent in pigs and presumably in man. A difference in plasma calcium might represent a fundamental distinction if an artefact can be excluded and therefore needs to be carefully explored. The most puzzling observation in pigs, namely a 50 per cent increase in plasma magnesium within minutes of exposure to halothane, demands measurements of that parameter in man.