Source:http://linkedlifedata.com/resource/pubmed/id/18084979
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2007-12-18
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pubmed:abstractText |
Malignant hyperthermia is a pharmacogenetic disorder caused by autosomal dominant mutations in the ryanodine receptor type 1 gene. Propofol has been reported as a safe anaesthetic for malignant hyperthermia susceptible patients but has not been tested on cultured cells from patients with the ryanodine receptor type 1 mutation. The aim of this study was to determine whether propofol could trigger abnormal calcium fluxes in human myotubes isolated from malignant hyperthermia susceptible patients harbouring the native ryanodine receptor type 1 mutation. Muscle specimens were obtained from the patients to diagnose malignant hyperthermia disposition and the calcium-induced calcium release test and molecular genetic analyses were performed. Using the calcium sensitive probe Fura 2, we determined the 340/380 nm wave-length ratios by measuring alterations in calcium homeostasis in isolated myotubes from cultured skeletal muscle specimens. Two patients, one with ryanodine receptor type 1 R2508C and one with the L4838V mutation had accelerated calcium-induced calcium release rates. The 340/380 nm ratios increased when the propofol concentration exceeded 100 microM. The half-maximal activation concentrations (EC50) for propofol from patients 1 and 2 were 181.1 and 420.5 microM, respectively. Increases in calcium concentrations in response to propofol dosage were limited to doses at least 100-fold greater than those used in clinical settings. These observations correlate well with clinical observations that propofol does not trigger malignant hyperthermia in susceptible humans.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0310-057X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
894-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:18084979-Adolescent,
pubmed-meshheading:18084979-Anesthetics, Intravenous,
pubmed-meshheading:18084979-Calcium,
pubmed-meshheading:18084979-Cells, Cultured,
pubmed-meshheading:18084979-Female,
pubmed-meshheading:18084979-Humans,
pubmed-meshheading:18084979-Male,
pubmed-meshheading:18084979-Malignant Hyperthermia,
pubmed-meshheading:18084979-Middle Aged,
pubmed-meshheading:18084979-Molecular Biology,
pubmed-meshheading:18084979-Muscle Fibers, Skeletal,
pubmed-meshheading:18084979-Point Mutation,
pubmed-meshheading:18084979-Propofol,
pubmed-meshheading:18084979-Ryanodine Receptor Calcium Release Channel
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pubmed:year |
2007
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pubmed:articleTitle |
Propofol-induced changes in myoplasmic calcium concentrations in cultured human skeletal muscles from RYR1 mutation carriers.
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pubmed:affiliation |
Department of Anesthesiology and Critical Care, Hiroshima University, Hiroshima, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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