Hipertermia maligna: aspectos moleculares e clínicos

Ana Carolina de Carvalho Correia; Polyana Cristina Barros Silva; Bagnólia Araújo da Silva

doi:10.1590/S0034-70942012000600007

Review Article

Hipertermia maligna: aspectos moleculares e clínicos

Malignant hyperthermia: clinical and molecular aspects

Ana Carolina de Carvalho Correia; Polyana Cristina Barros Silva; Bagnólia Araújo da Silva

http://dx.doi.org/10.1590/S0034-70942012000600007 Braz J Anesthesiol, vol.62, n6, p.828-837, 2012

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Resumo

CONTEÚDO: A hipertermia maligna (HM) é uma doença farmacogenética potencialmente letal que acomete indivíduos geneticamente predispostos. Manifesta-se em indivíduos susceptíveis em resposta à exposição a anestésicos inalatórios, relaxantes musculares despolarizantes ou atividade física extrema em ambientes quentes. Durante a exposição a esses agentes desencadeadores, há um aumento rápido e sustentado da concentração de cálcio mioplasmático (Ca2+) induzido pela hiperativação dos receptores de rianodina (RYR1) do músculo esquelético, causando uma alteração profunda na homeostase de Ca2+, caracterizando um estado hipermetabólico. RYR1, canais de libertação de Ca2+ do retículo sarcoplasmático, é o principal local de susceptibilidade à HM. Várias mutações no gene que codifica a proteína RYR1 foram identificadas, mas outros genes podem estar envolvidos. Atualmente, o método padrão para o diagnóstico de sensibilidade à HM é o teste de contratura muscular para exposição ao halotano-cafeína (CHCT) e o único tratamento é o uso de dantroleno. No entanto, com os avanços no campo da genética molecular, um pleno entendimento da etiologia da doença pode ser fornecido, favorecendo o desenvolvimento de um diagnóstico preciso, menos invasivo, com o teste de ADN, e também proporcionar o desenvolvimento de novas estratégias terapêuticas para o tratamento da HM. Logo, esta breve revisão tem como objetivo integrar os aspectos clínicos e moleculares da HM, reunindo informações para uma melhor compreensão desta canalopatia.

Palavras-chave

ANESTÉSICOS, Volátil, BLOQUEADOR MUSCULAR, Cálcio, Hipertermia Maligna, Rianodina

Abstract

CONTENT: Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disorder that affects genetically predisposed individuals. It manifests in susceptible individuals in response to exposure to Inhalant anesthetics, depolarizing muscle relaxants or extreme physical activity in hot environments. During exposure to these triggering agents, there is a rapid and sustained increase of myoplasmic calcium (Ca2+) concentration induced by hyperactivation of ryanodine receptor of skeletal muscle (RyR1), causing a profound change in Ca2+ homeostasis, featuring a hypermetabolic state. RyR1, Ca2+ release channels of sarcoplasmic reticulum, is the primary locus for MH susceptibility. Several mutations in the gene encoding the protein RyR1 have been identified; however, other genes may be involved. Actually, the standard method for diagnosing MH susceptibility is the muscle contracture test for exposure to halothane-caffeine (CHCT) and the only treatment is the use of dantrolene. However, with advances in molecular genetics, a full understanding of the disease etiology may be provided, favoring the development of an accurate diagnosis, less invasive, with DNA test, and also will provide the development of new therapeutic strategies for treatment of MH. Thus, this brief review aims to integrate molecular and clinical aspects of MH, gathering input for a better understanding of this channelopathy.

Keywords

Anesthetics, Inhalation, Calcium, Malignant Hyperthermia, Neuromuscular Blocking Agents, Ryanodine

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Hipertermia maligna: aspectos moleculares e clínicos

Malignant hyperthermia: clinical and molecular aspects

Ana Carolina de Carvalho Correia; Polyana Cristina Barros Silva; Bagnólia Araújo da Silva

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