OBJECTIVE: Statins (3-hydroxymethylglutaryl-coenzyme A reductase inhibitor) are widely used to treat hypercholesterolemia. They are generally well tolerated, but myotoxic effects have been reported and the corresponding mechanisms are still a matter of debate. The aim of the present study was to determine whether impairment of calcium homeostasis and/or mitochondrial impairment could account for the adverse effects of statins in skeletal muscle. METHODS: Eleven patients with increased creatine kinase levels and myalgias after statin treatment were evaluated using in vitro contracture tests (IVCTs), histology, and 31P magnetic resonance spectroscopy (31P-MRS). RESULTS: IVCT results were abnormal in 7 of the 9 patients, indicating an impaired calcium homeostasis. The 31P-MRS investigation disclosed no anomaly at rest, and the aerobic function assessed during the postexercise recovery period was normal. On the contrary, the pH recovery kinetics was significantly slowed down as indicated by a reduced proton efflux, which could be ultimately linked to a failure of calcium homeostasis. Overall, our observations indicate a normal mitochondrial function and raise the possibility that statins may unmask a latent pathology involving an impairment of calcium homeostasis such as malignant hyperthermia (MH). CONCLUSION: In case of susceptibility to MH, statins treatment must be administered with caution, and signs of adverse effects should be checked.
OBJECTIVE: Statins (3-hydroxymethylglutaryl-coenzyme A reductase inhibitor) are widely used to treat hypercholesterolemia. They are generally well tolerated, but myotoxic effects have been reported and the corresponding mechanisms are still a matter of debate. The aim of the present study was to determine whether impairment of calcium homeostasis and/or mitochondrial impairment could account for the adverse effects of statins in skeletal muscle. METHODS: Eleven patients with increased creatine kinase levels and myalgias after statin treatment were evaluated using in vitro contracture tests (IVCTs), histology, and 31P magnetic resonance spectroscopy (31P-MRS). RESULTS: IVCT results were abnormal in 7 of the 9 patients, indicating an impaired calcium homeostasis. The 31P-MRS investigation disclosed no anomaly at rest, and the aerobic function assessed during the postexercise recovery period was normal. On the contrary, the pH recovery kinetics was significantly slowed down as indicated by a reduced proton efflux, which could be ultimately linked to a failure of calcium homeostasis. Overall, our observations indicate a normal mitochondrial function and raise the possibility that statins may unmask a latent pathology involving an impairment of calcium homeostasis such as malignant hyperthermia (MH). CONCLUSION: In case of susceptibility to MH, statins treatment must be administered with caution, and signs of adverse effects should be checked.
Authors: Annette Draeger; Verónica Sanchez-Freire; Katia Monastyrskaya; Hans Hoppeler; Matthias Mueller; Fabio Breil; Markus G Mohaupt; Eduard B Babiychuk Journal: Am J Pathol Date: 2010-05-20 Impact factor: 4.307
Authors: Sheila Riazi; Natalia Kraeva; Sheila M Muldoon; James Dowling; Clara Ho; Maria-Alexandra Petre; Jerome Parness; Robert T Dirksen; Henry Rosenberg Journal: Can J Anaesth Date: 2014-09-05 Impact factor: 5.063
Authors: Paul J Isackson; Heather M Ochs-Balcom; Changxing Ma; John B Harley; Wendy Peltier; Mark Tarnopolsky; Naganand Sripathi; Robert L Wortmann; Zachary Simmons; Jon D Wilson; Stephen A Smith; Alexandru Barboi; Edward Fine; Alan Baer; Steven Baker; Kenneth Kaufman; Beth Cobb; Jeffrey R Kilpatrick; Georgirene D Vladutiu Journal: Muscle Nerve Date: 2011-08-08 Impact factor: 3.217
Authors: Georgirene D Vladutiu; Paul J Isackson; Kenneth Kaufman; John B Harley; Beth Cobb; Lisa Christopher-Stine; Robert L Wortmann Journal: Mol Genet Metab Date: 2011-07-12 Impact factor: 4.797