• Takako Migita, Keiko Mukaida, Toshimichi Yasuda, Hiroshi Hamada, and Masashi Kawamoto.
• Division of Anesthesia, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, 1-9-6 Senda-machi, Naka-ku, Hiroshima, 730-8619, Japan. t-migita@hiroshima-med.jrc.or.jp
• J Anesth. 2012 Aug 1;26(4):579-84.

PurposeMalignant hyperthermia (MH) results from disordered calcium (Ca(2+)) homeostasis in skeletal muscle during general anesthesia. Although Ca(2+) channel blockers may be given to treat the tachycardia and circulatory instability, coadministration of Ca(2+) channel blockers and dantrolene is contraindicated during MH crisis. We evaluated the effect of Ca(2+) channel blockers on Ca(2+) homeostasis and their interactions with dantrolene in human skeletal muscle.MethodsHuman skeletal muscle samples were obtained by biopsy and divided into two groups according to the results of the Ca(2+)-induced Ca(2+) release rate test. Differentiated myotubes were labeled with Fura-2, and changes in the 340/380-nm ratio were used to calculate changes in Ca(2+) concentration following nifedipine treatment in the absence or presence of dantrolene.ResultsNifedipine induced a transient increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in a dose-dependent manner. The half-maximal concentration (EC(50)) for nifedipine was 0.718 ± 0.329 μM in the accelerated group and 1.389 ± 0.482 μM in the nonaccelerated group (P = 0.009). The addition of 50 μM dantrolene attenuated by 15.4% the increase in [Ca(2+)](i) caused by the 0.5 μM nifedipine.ConclusionCa(2+) channel blockers led to increased [Ca(2+)](i) in human skeletal muscle cells. The increase is thus scarcely affected by dantrolene treatment. Data provide a greater physiologic basis for avoiding the use of Ca(2+) channel blockers during MH crisis.

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