| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Cardiovascular Therapeutics | ||||
| Publisher: | WILEY-BLACKWELL | ||||
| Place of Publication: | MALDEN | ||||
| Volume: | 28 | ||||
| Number of Issue or Book Chapter: | 6 | ||||
| Page Range: | pp. 356-360 | ||||
| Date: | 2010 | ||||
| Institutions: | Medicine > Lehrstuhl für Anästhesiologie | ||||
| Identification Number: |
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| Keywords: | SKELETAL-MUSCLE PREPARATIONS; IN-VITRO; RHABDOMYOLYSIS; MYOPATHY; CERIVASTATIN; MYOTOXICITY; INHIBITION; MECHANISMS; UBIQUINONE; DIAGNOSIS; Malignant hyperthermia; Myotoxicity; Statins | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 66507 |
Web of ScienceAbstract
Aims: Statines, HMG-CoA reductase inhibitors, are widely used to treat hypercholesterinemia. These substances are well tolerated, but myotoxic effects have been reported. The exact mechanisms of the induced myotoxicity are unknown but an involvement of intracellular calcium handling is suspected. Individuals susceptible to malignant hyperthermia (MH) have an impaired calcium homeostasis. An in ...
Abstract
Aims: Statines, HMG-CoA reductase inhibitors, are widely used to treat hypercholesterinemia. These substances are well tolerated, but myotoxic effects have been reported. The exact mechanisms of the induced myotoxicity are unknown but an involvement of intracellular calcium handling is suspected. Individuals susceptible to malignant hyperthermia (MH) have an impaired calcium homeostasis. An in vitro test measuring contracture responses of isolated muscle bundles is used to investigate cellular processes of MH. Aim of this study was to investigate if statins modify the contracture response of isolated muscle bundles from MH susceptible (MHS) and nonsusceptible (MHN) pigs. Methodology: With approval of the local ethics committee muscle biopsies of 18 MH susceptible and 12 nonsusceptible pigs were performed. Muscle bundles were mounted on an isometric force transducer, preloaded, and electrically stimulated. After establishment of a stable baseline, muscle bundles were exposed to simvastatin, atorvastatin, gemfibrocil, and the pure solvent. Baseline tension was measured and analyzed for changes with P < 0.05 considered to be significant. Results: There were no differences in weight, length, and predrug baseline tension between the groups. Both simvastatin and atorvastatin induced significant contractures in muscle bundles from MHS pigs. Gemfibrocil and the solvent methanol showed no effect. In MHN muscle bundles, none of the tested substances induced a contracture. Statines induce contractures only in MHS muscle bundles. Conclusion: We therefore conclude that the underlying mechanism may be a pathologic influence on intracellular calcium handling that is absent in MHN. A preexisting impairment of the calcium homeostasis seems to be necessary for this behavior because muscle bundles of MHN pigs showed no pathologic reaction. A higher muscle cell vulnerability toward statins is assumed in MHS patients. Statins ought to be used with caution in these individuals. Analogous a diagnostic workup for MH should be considered for patients with statin-induced rhabdomyolyis.
Metadata last modified: 19 Dec 2024 11:44
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