Summary
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.
Résumé
Ľétiologie de ľhyperthermie maligne demeure encore incertaine, cependant la recherche cerne la vérité de plus en plus. En ce moment, les constatations expérimentales et cliniques disponibles nous incitent à croire que le point défectueux est périphérique plutôt que central. Du moins, en ce qui concerne les cas qui présentent de la rigidité; il ne semble pas que le facteur causal soit ou ľabsence ďunion de la phosphorylation oxidative, ou ľabsence de phosphorylase du muscle, ou un trouble de ľactivité de ľatp des membranes cellulaires ou le défaut dans la dystrophic myotonique.
Ľhyperthermie maligne observée sur la base de défauts génétiques chez les porcs Landrace est identique non seulement au syndrome clinique humain, mais aussi à plusieurs aspects biochimiques. Les modifications du métabolisme des hydrates de carbone comme ľindique ľaccumulation de ľacide lactique est un point prédominant chez les porcs et, nous le présumons, chez ľhomme. Une différence dans le taux de calcium plasmatique peut constituer une distinction fondamentale si ľon peut exclure un artefact et, alors, il faut faire des recherches minutieuses. Ľobservation la plus troublante chez les porcs consiste en une augmentation de 50 pour cent du magnesium plasmatique en deçà de quelques minutes après ľinhalation ďhalothane; chez ľhumain, il nous faut mesurer ce paramètre.
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Brut, B.A., Kalow, W. Malignant hyperthermia: Aetiology unknown. Can. Anaesth. Soc. J. 17, 316–330 (1970). https://doi.org/10.1007/BF03004695
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DOI: https://doi.org/10.1007/BF03004695