[The perioperative period: how drugs should be managed?]. / Médicaments en période périopératoire, que faire?

Medication use during the perioperative period can raise problems in surgical patients. Elderly patients are especially at risk because of polymedication. Risks pertaining to each drug should be carefully evaluated. For example, several drugs can affect coagulation and discontinuation of others can lead to withdrawal symptoms. We suggest here recommendations based on recent publications. It should be kept in mind that, apart from the drug itself, the patient status as well as the surgical procedure also influence the decision to stop or continue a medication. Moreover, it is important to plan to restart any discontinued drug in order to avoid unintended treatment failure after hospital discharge.

Mitochondrial calcium oscillations in C2C12 myotubes.

Mitochondrial Ca(2+) concentration ([Ca(2+)](m)) was monitored in C2C12 skeletal muscle cells stably expressing the Ca(2+)-sensitive photoprotein aequorin targeted to mitochondria. In myotubes, KCl-induced depolarization caused a peak of 3.03 +/- 0.14 micrometer [Ca(2+)](m) followed by an oscillatory second phase (5.1 +/- 0.1 per min). Chelation of extracellular Ca(2+) or blockade of the voltage-operated Ca(2+) channel attenuated both phases of the KCl response. The inhibitor of the sarcoplasmic reticulum Ca(2+)-ATPase, cyclopiazonic acid, reduced the amplitude of the KCl-induced [Ca(2+)](m) peak and prevented the oscillations, suggesting that these were generated intracellularly. No such [Ca(2+)](m) oscillations occurred with the nicotinic agonist carbachol, cyclopiazonic acid alone, or the purinergic agonist ATP. In contrast, caffeine produced an oscillatory behavior, indicating a role of ryanodine receptors as mediators of the oscillations. The [Ca(2+)](m) response was desensitized when cells were exposed to two consecutive challenges with KCl separated by a 5-min wash, whereas a second pulse of carbachol potentiated [Ca(2+)](m), indicating differences in intracellular Ca(2+) redistribution. Cross-desensitization between KCl and carbachol and cross-potentiation between carbachol and KCl were observed. These results suggest that close contacts between mitochondria and sarcoplasmic reticulum exist permitting Ca(2+) exchanges during KCl depolarization. These newly demonstrated dynamic changes in [Ca(2+)](m) in stimulated skeletal muscle cells might contribute to the understanding of physiological and pathological processes in muscular disorders.

Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells.

Dystrophic skeletal muscle cells from Duchenne muscular dystrophy (DMD) patients and mdx mice exhibit elevated cytosolic Ca2+ concentrations ([Ca2+]c). Pretreatment of mdr myotubes for 6-12 days with creatine (20 mM) decreased the elevation in [Ca2+]c induced by either high extracellular Ca2+ concentrations or hypo-osmotic stress to control levels. 45Ca2+ influx measurements suggest that creatine lowered [Ca2+]c by stimulating sarcoplasmic reticulum Ca2+-ATPase. Creatine pretreatment increased levels of phosphocreatine but not ATP. Furthermore, myotube formation and survival were significantly enhanced by creatine pretreatment. Therefore, creatine supplementation may be useful for treatment of DMD.