Screening for Malignant Hyperpyrexia

Ellis, F. R.; Keaney, N. P.; Harriman, D. G. F.; Sumner, David; Kyei-Mensah, K.; Tyrrell, Jean; Hargreaves, Janet; Parikh, R. K.; Mulrooney, Patrick

doi:10.1097/00132586-197308000-00034

Cited by 8 publications

(8 citation statements)

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“…1.2), accounting for the abnormality in roughly 40% of MH families (Loke and MacLennan, 1998 Ellis et al, 1972;Mickelson and Louis, 1996;Otsu et al, 1994;Treves et al, 1994;Tong et al, 1997). Dantrolene is an antidote to an MH crisis (Harrison, 1975) through its apparent ability to close Gaz+ release channels.…”

Section: Malignant Hyperthermiamentioning

confidence: 99%

Complex interactions between skeletal muscle ryanodine receptor and dihydropyridine receptor proteins

Leong¹,

MacLennan²

1998

Biochem. Cell Biol.

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Evidence for functional interactions between the Ca2+ release channel in the skeletal muscle sarcoplasmic reticulum (the ryanodine receptor) and the L-type Ca2+ channel in the sarcolemma (the dihydropyridine receptor), leading to excitation-contraction coupling, is reviewed and experimental systems used to identify candidate sites of interaction are outlined.Key words: sarcoplasmic reticulum, excitation-contraction coupling.

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Section: Malignant Hyperthermiamentioning

confidence: 99%

Complex interactions between skeletal muscle ryanodine receptor and dihydropyridine receptor proteins

Leong¹,

MacLennan²

1998

Biochem. Cell Biol.

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“…10,17,26,74,81,99,101,108,109,141,143,145,146,150,158,187,188,189 This is not to say that the defects must be confined to skeletal muscle, nor does this necessarily mean that a defect in muscle is the primary lesion. 99,14~…”

Section: Introductionmentioning

confidence: 99%

Malignant hyperthermia: an investigation of five patients

Britt

Kalow

Gordon

et al. 1973

Canad. Anaesth. Soc. J.

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“…Higher caffeine sensitivity is observed in RyR1 mutants and probably explains the usefulness of caffeine for malignant hyperthermia diagnostic purpose [23]. Twenty minutes before exposure to the same concentrations of azumolene and dantrolene sodium (10 μM) significantly reduced but did not abolish the caffeine-induced contractures in SOL muscle of mice.…”

Section: Discussionmentioning

confidence: 94%

Effects of Azumolene on Normal and Malignant Hyperthermia‐Susceptible Skeletal Muscle

Sudo

Carmo

Trachez

et al. 2007

Basic Clin Pharma Tox

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Malignant hyperthermia is a pharmacogenetic disease of skeletal muscle in which a life-threatening, hypermetabolic syndrome is induced by exposure of susceptible patients to halogenated general anaesthetics and/or succinylcholine. Dantrolene sodium, the only drug effective for treatment of malignant hyperthermia, has low water solubility that makes its clinical use difficult. The aim of this study was to investigate the potency of azumolene, a 30-fold more water-soluble analogue, in comparison to the prototype dantrolene sodium, on mammalian and human skeletal muscles. The twitches of extensor digitorum longus and soleus muscles from mice were inhibited by azumolene with IC 50 of 2.8 ± 0.8 and 2.4 ± 0.6 μ M, respectively. The IC 50 of dantrolene sodium in these muscles was 1.6 ± 0.4 and 3.5 ± 1.2 μ M, respectively, with no difference in comparison to azumolene. Previous in vitro exposure of mouse soleus muscle to azumolene and dantrolene sodium (10 μ M) significantly inhibited 8 mM caffeine-induced contractures. Azumolene was just effective as dantrolene sodium in relaxing caffeine-induced contractures of mouse soleus muscle. Intravenous injection caused dose-dependent decreases in twitches of guinea pig gastrocnemius muscle with IC 50 of 1.2 ± 0.1 and 1.5 ± 0.2 mg/kg for azumolene and dantrolene sodium, respectively. Azumolene, 10 μ M, was effective in blocking and reversing caffeine-induced contracture of human malignant hyperthermia susceptible skeletal muscle in vitro . These studies provide evidence that azumolene is equipotent to dantrolene sodium in blocking pharmacologic-induced muscle contractures and that azumolene should be efficacious for treatment/prevention of malignant hyperthermia.Malignant hyperthermia is a pharmacogenetic disorder characterized by abnormal increase of Ca 2+ release from sarcoplasmic reticulum triggered by volatile halogenated anaesthetics and/or succinylcholine [1]. The cause for malignant hyperthermia and consequently the dysregulation of myoplasmic Ca 2+ is related to a mutation of the Ca 2+ release channel (RyR1) of sarcoplasmic reticulum [2,3]. RyR1 causal mutations have been found in over 50% of malignant hyperthermiasusceptible families [4]. Dantrolene, 1-<{[5-(4-nitrophenyl)-2-furfuryl]methylene}amino>-2,4-imidazoleidinedione, is the only drug effective for treatment and prevention of malignant hyperthermia and as a consequence of its clinical introduction, mortality decreased from 70% to 5 -10% [5]. Dantrolene is a skeletal muscle relaxant that modulates the activity of RyR1 promoting inhibition of Ca 2+ efflux from sarcoplasmic reticulum [6,7]. The treatment of a malignant hyperthermia episode consists of an initial intravenous injection of 2.5 mg/kg of dantrolene sodium [8]. Due to low water solubility (about 0.3 mg/ml) this amount of dantrolene sodium must be dissolved in about 500 ml of water in a 70-kg patient that represents risks from consuming time and for aggravating the cardiac failure usually present in an malignant hyperthermia crisis. A 30-fold mo...

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Screening for Malignant Hyperpyrexia

Cited by 8 publications

References 1 publication

Complex interactions between skeletal muscle ryanodine receptor and dihydropyridine receptor proteins

Complex interactions between skeletal muscle ryanodine receptor and dihydropyridine receptor proteins

Malignant hyperthermia: an investigation of five patients

Effects of Azumolene on Normal and Malignant Hyperthermia‐Susceptible Skeletal Muscle

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