Abnormal uptake and release of Ca 2+ ions from human malignant hyperthermia-susceptible sarcoplasmic reticulum 1 1Abbreviations: CICR, Ca2+-induced Ca2+ release; HEK-293, human embryonic kidney; HSR, heavy sarcoplasmic reticulum; IVCT, in vitro caffeine halothane contracture test; MH, malignant hyperthermia; MHS, malignant hyperthermia-susceptible; MHN, malignant hyperthermia normal; MOPS, 3-[N-Morpholino]propanesulphonic acid; RYR1, ryanodine receptor skeletal muscle gene; and TFP, trifluoperazine.

O’Sullivan, Grainne; McIntosh, James M.; Heffron, J. J. A.

doi:10.1016/s0006-2952(01)00604-9

Cited by 28 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Heavy SR was prepared from hind limb muscles of rats as previously described [25,27]. Ca 2+ release was measured by spectrophotometry using a HP 8452A diode-array spectrophotometer operating in dual wavelength mode at 710 nm and 790 nm at 37°C with constant magnetic cuvette stirring.…”

Section: Methodsmentioning

confidence: 99%

“…Controls showed that ethanol had no effect at the concentrations used. SR protein concentration was measured as previously reported [25,27]. Anesthetic concentrations in the cuvette reaction medium were analyzed using electron capture gas chromatography.…”

Section: Methodsmentioning

confidence: 99%

“…Anesthetic concentrations in the cuvette reaction medium were analyzed using electron capture gas chromatography. The three anesthetics were first purified by distillation [27]. …”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study

Klingler

Heiderich

Girard

et al. 2014

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundMalignant hyperthermia (MH) is a rare pharmacogenetic disorder which is characterized by life-threatening metabolic crises during general anesthesia. Classical triggering substances are volatile anesthetics and succinylcholine (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle principally by a mutated ryanodine receptor type 1 (RyR1). To identify factors explaining the variable phenotypic presentation and complex pathomechanism, we analyzed proven MH events in terms of clinical course, muscle contracture, genetic factors and pharmocological triggers.MethodsIn a multi-centre study including seven European MH units, patients with a history of a clinical MH episode confirmed by susceptible (MHS) or equivocal (MHE) in vitro contracture tests (IVCT) were investigated. A test result is considered to be MHE if the muscle specimens develop pathological contractures in response to only one of the two test substances, halothane or caffeine. Crises were evaluated using a clinical grading scale (CGS), results of IVCT and genetic screening. The effects of SCh and volatile anesthetics on Ca2+ release from sarcoplasmic reticulum (SR) were studied in vitro.ResultsA total of 200 patients met the inclusion criteria. Two MH crises (1%) were triggered by SCh (1 MHS, 1 MHE), 18% by volatile anesthetics and 81% by a combination of both. Patients were 70% male and 50% were younger than 12 years old. Overall, CGS was in accord with IVCT results. Crises triggered by enflurane had a significantly higher CGS compared to halothane, isoflurane and sevoflurane. Of the 200 patients, 103 carried RyR1 variants, of which 14 were novel. CGS varied depending on the location of the mutation within the RyR1 gene. In contrast to volatile anesthetics, SCh did not evoke Ca2+ release from isolated rat SR vesicles.ConclusionsAn MH event could depend on patient-related risk factors such as male gender, young age and causative RyR1 mutations as well as on the use of drugs lowering the threshold of myoplasmic Ca2+ release. SCh might act as an accelerant by promoting unspecific Ca2+ influx via the sarcolemma and indirect RyR1 activation. Most MH crises develop in response to the combined administration of SCh and volatile anesthetics.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study

Klingler

Heiderich

Girard

et al. 2014

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…The pathophysiology of MH is caused by uncontrolled calcium release from the sarcoplasmic reticulum into intracellular space, following exposure to an inducing agent. 5 A rise in intracellular calcium results in sustained activation and contraction of muscle cells. Once adenosine triphosphate (ATP) is depleted, the skeletal muscles begin to break down, releasing potassium and myoglobin.…”

Section: Discussionmentioning

confidence: 99%

A Case Report of an Incidental Ultrasound Finding in a Suspected Malignant Hyperthermia Patient

2022

A&A Practice

View full text Add to dashboard Cite

Malignant hyperthermia (MH) is a rare but life-threatening genetic disorder of the skeletal muscles triggered by inhalation anesthetics or succinylcholine. A 49-year-old female developed symptoms of MH shortly after a lumbar surgery. Despite being insidious, MH was diagnosed based on the clinical grading scale. We incidentally discovered fine fasciculations in extremities while inserting an ultrasound-guided arterial catheter. On receiving dantrolene, her symptoms improved within 20 minutes; a subsequent ultrasound revealed no fasciculations. Although halothane contracture testing was not available, the fasciculations that resolved with dantrolene administration in a MH suspected patient opens up a new potential avenue of diagnostics. (A&A Practice. 2022;16:e01651.) GLOSSARYABG = arterial blood gas; ALS = amyotrophic lateral sclerosis; ATP = adenosine triphosphate; BP = blood pressure; CK-MB = creatine kinase MB; CK-total = creatine kinase total; EQUATOR = Enhancing the QUAlity and Transparency Of health Research; ICU = intensive care unit; IVCT = in vitro contracture testing; MH = malignant hyperthermia; NMS = neuroleptic malignant syndrome; PACU = postanesthesia care unit; TSH = thyroid stimulating hormoneFigure. Timeline of the episode of malignant hyperthermia. ABG indicates arterial blood gas; BP , blood pressure; CK-MB, creatine kinase MB; PACU, postanesthesia care unit.

show abstract

Malignant Hyperthermia

Litman¹,

Rosenberg²

2005

JAMA

169

View full text Add to dashboard Cite

Cited by 28 publications

References 30 publications

Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study

Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study

A Case Report of an Incidental Ultrasound Finding in a Suspected Malignant Hyperthermia Patient

Malignant Hyperthermia

Contact Info

Product

Resources

About