Exertional heat stroke, rhabdomyolysis and susceptibility to malignant hyperthermia

Thomas, Josephine; Crowhurst, Thomas

doi:10.1111/imj.12232

Cited by 22 publications

(13 citation statements)

References 24 publications

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“…In the available muscle biopsies from 15 patients, most showed fiber size variability, increased internalized nuclei, type 1 fiber predominance, and core-like areas on oxidative stains. The link between exertional heat stroke, rhabdomyolysis, and susceptibility to malignant hyperthermia has not been characterized fully 194, 195 .…”

Section: Genetic Causes Of Rhabdomyolysismentioning

confidence: 99%

Diagnostic evaluation of rhabdomyolysis

2015

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Rhabdomyolysis is characterized by severe acute muscle injury resulting in muscle pain, weakness, and/or swelling with release of myofiber contents into the bloodstream. Symptoms develop over hours to days following an inciting factor and may be associated with dark pigmentation of the urine. Serum creatine kinase and urine myoglobin levels are markedly elevated. The clinical examination, history, laboratory studies, muscle biopsy, and genetic testing are useful tools for diagnosis of rhabdomyolysis, and they can help differentiate acquired from inherited causes of rhabdomyolysis. Acquired causes include substance abuse, medication or toxic exposures, electrolyte abnormalities, endocrine disturbance, and autoimmune myopathies. Inherited predisposition to rhabdomyolysis can occur with disorders of glycogen metabolism, fatty acid beta-oxidation, and mitochondrial oxidative phosphorylation. Less common inherited causes of rhabdomyolysis include structural myopathies, channelopathies, and sickle cell disease. This review focuses on the differentiation of acquired and inherited causes of rhabdomyolysis and proposes a practical diagnostic algorithm.

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Section: Genetic Causes Of Rhabdomyolysismentioning

confidence: 99%

Diagnostic evaluation of rhabdomyolysis

2015

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“…Variants in the RyR1 gene have been associated with MH in 50% to 70% of susceptible families 48 . There are reports of rhabdomyolysis and exertional myalgia associated with positive IVCT 49 and RyR1 gene mutations and dihydropyridine receptor mutations 46,[50][51][52][53] and hence, the supposed association of MH with stress. Heatrelated events corresponding to recent findings in animal models of MH susceptibility and, in one family, intercurrent infection 51 , have been associated with RyR1 variants 54 .…”

Section: Discussionmentioning

confidence: 99%

Safe Duration of Postoperative Monitoring for Malignant Hyperthermia Patients Administered Non-Triggering Anaesthesia: An Update

Barnes

Stowell

Bulger

et al. 2015

Anaesth Intensive Care

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The postoperative care of malignant hyperthermia (MH) patients is subject to international variation, with a paucity of data in the literature to guide management. Over a series of three studies, our aim was to evaluate whether MH-susceptible patients (and relatives who had not yet been investigated), who had received a non-triggering anaesthetic, could be managed in the same way as the standard surgical population. Following a retrospective study, 206 anaesthetics were administered in a prospective second study to MH-susceptible/related individuals who were monitored for a minimum of one hour in the post anaesthesia care unit and a further 90 minutes in a step-down facility. No problems relating to MH were encountered. The postoperative monitoring time was subsequently changed and, in a third study, patients were managed no differently from standard surgical patients. One hundred and twenty-five anaesthetics were administered with no evidence of problems. This data shows that standard postoperative monitoring times are safe and appropriate in MH-susceptible patients.

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“…Whether any of the 400þ MHS mutations confer risk to skeletal muscle health with prolonged CP exposure remains a difficult question to address. Although there are numerous documented cases of MHS individuals who experienced nonfatal episodes and spontaneously developed muscle weakness or rhabdomyolysis following exposure to environmental stressor(s) (Dlamini et al, 2013;Thomas and Crowhurst 2013), whether CP, FD, or other insecticide diamides interact with MHS RyR1 channels to lower the threshold for developing chronic myopathies remains unknown.…”

Section: Relevance and Rationale Of Acute Cp Dose To Assess Influencementioning

confidence: 99%

Comparison of Chlorantraniliprole and Flubendiamide Activity Toward Wild-Type and Malignant Hyperthermia-Susceptible Ryanodine Receptors and Heat Stress Intolerance

Truong¹,

Pessah

2018

Toxicological Sciences

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Chlorantraniliprole (CP) and flubendiamide (FD) are widely used in agriculture globally to control lepidopteran pests. Both insecticides target ryanodine receptors (RyRs) and promote Ca 2þ leak from sarcoplasmic reticulum (SR) within insect skeletal muscle yet are purportedly devoid of activity toward mammalian RyR1 and muscle. RyRs are ion channels that regulate intracellular Ca 2þ release from SR during physiological excitation-contraction coupling. Mutations in RYR1 genes confer malignant hyperthermia susceptibility (MHS), a potentially lethal pharmacogenetic disorder in humans and animals. Compared with vehicle control, CP (10 mM) triggers a 65-fold higher rate of Ca 2þ efflux from Ca 2þ-loaded mammalian WT-RyR1 SR vesicles, whereas FD (10 mM) produces negligible influence on Ca 2þ leak. We, therefore, compared whether CP or FD differentially influence patterns of high-affinity [ 3 H]ryanodine ([ 3 H]Ry) binding to RyR1 isolated from muscle SR membranes prepared from adult C57BL/6J mice expressing WT, homozygous C-terminal MHS mutation T4826I, or heterozygous Nterminal MHS mutation R163C. Basal [ 3 H]Ry binding differed among genotypes with rank order T4826I)R163C$WT, regardless of [Ca 2þ ] in the assay medium. Both CP and FD (0.01-100 mM) elicited concentration-dependent increase in [ 3 H]Ry binding, although CP showed greater efficacy regardless of genotype or [Ca 2þ ]. Exposure to CP (500 mg/kg; p.o) failed to shift intolerance to heat stress (38 C) characteristic of R163C and T4826I MHS mice, nor cause lethality in WT mice. Although nM-mM of either diamide is capable of differentially altering WT and MHS RyR1 conformation in vitro, human RyR1 mutations within putative diamide N-and C-terminal interaction domains do not alter heat stress intolerance (HSI) in vivo.

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Exertional heat stroke, rhabdomyolysis and susceptibility to malignant hyperthermia

Cited by 22 publications

References 24 publications

Diagnostic evaluation of rhabdomyolysis

Diagnostic evaluation of rhabdomyolysis

Safe Duration of Postoperative Monitoring for Malignant Hyperthermia Patients Administered Non-Triggering Anaesthesia: An Update

Comparison of Chlorantraniliprole and Flubendiamide Activity Toward Wild-Type and Malignant Hyperthermia-Susceptible Ryanodine Receptors and Heat Stress Intolerance

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