title: Calcium channel blockers are inadequate for malignant hyperthermia crisis.
abstract: OBJECTIVE
  Malignant 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.
  
  
  METHODS
  Human 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.
  
  
  RESULTS
  Nifedipine 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.
  
  
  CONCLUSIONS
  Ca(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.
authors.affiliation: 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
authors.forename: Takako
authors.initials: T
authors.lastname: Migita
authors.forename: Keiko
authors.initials: K
authors.lastname: Mukaida
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003620:Dantrolene / Q000494:pharmacology; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000648:ultrastructure; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D055815:Young Adult
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009125:Muscle Relaxants, Central; D003620:Dantrolene; D009543:Nifedipine; D002118:Calcium