Exploring the Relationship Between Malignant Hyperthermia, and Exertional Heat Illness.

Oral presentation: Section B

Malignant Hyperthermia (MH) and Exertional heat illness (EHI) are hypothesized to be related syndromes. MH is an autosomal dominant, inherited, genetically heterogeneous myopathy that is characterized by a dysregulation of intracellular calcium homeostasis in skeletal muscle. MH is induced by volatile anesthetic agents and depolarizing muscle relaxants. Fulminant MH episodes, typically induced in apparently healthy young individuals are characterized by hypermetabolism, metabolic acidosis, muscle rigidity, rhabdomyolysis and hyperthermia [1]. It has been suggested that MH might be induced by physical exercise and emotional stress in the absence of anesthesia, an event well known in genetically determined breeds of swine. For many years, the skeletal muscle biopsy utilizing the caffeine halothane contracture test (CHCT) was the only validated diagnostic test available for MH. Recent molecular genetic studies have identified the primary locus of MH to chromosome 19. Mutations in the ryanodine receptor type 1 (RYR1) are known to cause MH susceptibility in at least 50% of cases. The RYR1 gene encodes a calcium channel that controls calcium release in skeletal muscle and has a central role in muscle contraction.

Exertional heat illness is a hyperthermic state in which heat is produced by muscular work at a rate that exceeds the body's capacity to dissipate it. Major preventive efforts such as maintenance of good hydration, limiting exercise intensity and metabolic heat production have reduced but not eliminated EHI episodes. Recent concepts about the etiology of EHI are based on (a) evidence for the involvement of inflammatory mediators in the pathogenesis of heat illness, (b) that the role of exercise (and thus, presumably of skeletal muscle) in the pathogenesis goes beyond exercise-related heat production and resulting thermal stress, and (c) that genetic susceptibility to MH is associated with a markedly increased risk of EHI [2]. Abnormalities in the caffeine–halothane contracture tests have been reported in 32% of a group of 250 French Commandos who suffered exertional heat stroke. Recently three distinct mutations in the RYR1 gene have been identified in patients with exercise –induced rhabdomyolyis and heat stroke [3]. In addition there is evidence that recent or concurrent infections increase the risk of both EHI and MH suggesting that the pathogenesis of EHI and MH may share common features.

References

1. Rosenberg H, Antognini JF, Muldoon S: Testing for malignant hyperthermia.

   Anesthesiology 2002, 96:232-237. PubMed Abstract | Publisher Full Text

2. Bouchama A, Knochel JP: Heat stroke.

   N Engl J Med 2002, 346:1978-1988. PubMed Abstract | Publisher Full Text

3. Tobin JR, Jason DR, Challa VR, Nelson TE, Sambuughin N: Malignant hyperthermia and apparent heat stroke.

   JAMA 2001, 286:168-169. PubMed Abstract | Publisher Full Text

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