Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-6-8
pubmed:abstractText
Malignant hyperthermia is a pharmacogenetic skeletal muscle disorder of intracellular calcium (Ca2+) homeostasis with an autosomal dominant inheritance. The objective of this study was to investigate the safety of propofol by investigating its effects on calcium homeostasis and its effect sites in human skeletal muscles. Muscle specimens were obtained from 10 individuals with predisposition to malignant hyperthermia. In skinned fibre experiments, we measured the effects of propofol on the Ca(2+)-induced Ca2+ release and the uptake of Ca2+ into the sarcoplasmic reticulum. Ca2+ imaging in primary myotubes was employed to analyse propofol-mediated alternations in the Ca2+ regulation and propofol-induced Ca2+ responses in the presence of Ca2+ channel blocker or Ca(2+)-induced Ca2+ release inhibitor. Increased Ca2+ release from the sarcoplasmic reticulum and inhibition of Ca2+ uptake into the sarcoplasmic reticulum were not observed with 100 microM propofol. A rise of Ca2+ was not seen under 100 microM propofol and the EC50 value for propofol was 274.7 +/- 33.9 microM, which is higher than the clinical levels for anaesthesia. Propofol-induced Ca2+ responses were remarkably attenuated in the presence of Ca2+ channel blocker or Ca(2+)-induced Ca+ release inhibitor compared with the results obtained with caffeine. We conclude firstly that propofol is safe for individuals with predisposition to malignant hyperthermia when it is used within the recommended clinical dosage range, and secondly that its mode of action upon ryanodine receptors is likely to be different from that of caffeine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0310-057X
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
415-25
pubmed:meshHeading
pubmed-meshheading:19499861-Adolescent, pubmed-meshheading:19499861-Adult, pubmed-meshheading:19499861-Aged, pubmed-meshheading:19499861-Anesthetics, Intravenous, pubmed-meshheading:19499861-Caffeine, pubmed-meshheading:19499861-Calcium, pubmed-meshheading:19499861-Child, pubmed-meshheading:19499861-Child, Preschool, pubmed-meshheading:19499861-Dose-Response Relationship, Drug, pubmed-meshheading:19499861-Female, pubmed-meshheading:19499861-Genetic Predisposition to Disease, pubmed-meshheading:19499861-Homeostasis, pubmed-meshheading:19499861-Humans, pubmed-meshheading:19499861-Male, pubmed-meshheading:19499861-Malignant Hyperthermia, pubmed-meshheading:19499861-Middle Aged, pubmed-meshheading:19499861-Muscle, Skeletal, pubmed-meshheading:19499861-Muscle Fibers, Skeletal, pubmed-meshheading:19499861-Propofol, pubmed-meshheading:19499861-Ryanodine Receptor Calcium Release Channel, pubmed-meshheading:19499861-Sarcoplasmic Reticulum
pubmed:year
2009
pubmed:articleTitle
Effects of propofol on calcium homeostasis in human skeletal muscle.
pubmed:affiliation
Department of Anesthesiology and Critical Care, Hiroshima University, Hiroshima, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't