title: The ryanodine contracture test may help diagnose susceptibility to malignant hyperthermia.
abstract: OBJECTIVE
  The ryanodine contracture test (RCT) using the plant alkaloid ryanodine as the triggering agent has been proposed to reduce equivocal results of the in vitro caffeine-halothane-contracture test (IVCT), which is the accepted and standardized procedure to diagnose malignant hyperthermia (MH). However, the response of skeletal muscle of non-MH affected patients (controls) to ryanodine has not yet been characterized.
  
  
  METHODS
  Skeletal muscle biopsies were studied in 33 controls and in six patients with a history of fulminant MH. Following the IVCT, the RCT was performed in all specimens using ryanodine 1 micro M. Onset time of contracture and time to reach a contracture level of 10 mN above lowest resting tension and above predrug tension were calculated.
  
  
  RESULTS
  With the standard IVCT, all controls were labelled MH non-susceptible; all clinically diagnosed MH patients were labelled MH susceptible. With ryanodine, control muscle differed from MH susceptible muscle regarding onset time of contracture (26 vs 3.8 min, P < 0.05) and time to reach a contracture of 10 mN (49 vs 12.5 min, P < 0.05; all median). Tissue viability and patient's age significantly influenced contracture times.
  
  
  CONCLUSIONS
  Despite the highly specific binding of ryanodine at the myocytic sarcoplasmic reticulum, the wide range of contracture times of the controls points toward heterogeneity of ryanodine receptors within physiologic limits. This may also be caused in part by tissue viability and the patients' age. The ryanodine contracture test performed in addition to the IVCT may add clarity into diagnosing a patient as MH-susceptible or not.
authors.affiliation: Department of Anesthesiology, University of Munich, Germany. Daniel.Reuter@ana.med.uni-muenchen.de
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Reuter
authors.forename: Martin
authors.initials: M
authors.lastname: Anetseder
authors.forename: Rainer
authors.initials: R
authors.lastname: Müller
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Hartung
mesh_terms: D000328:Adult; D000368:Aged; D018685:Anesthetics, Inhalation / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D006221:Halothane / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis / Q000209:etiology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D015203:Reproducibility of Results; D012433:Ryanodine / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D018685:Anesthetics, Inhalation; D012433:Ryanodine; D006221:Halothane