title: In vitro effects of 4-chloro-3-ethylphenol in skeletal muscle preparations from malignant hyperthermia susceptible and normal swine.
abstract: OBJECTIVE
  The in vitro contracture test with halothane and caffeine is the current gold standard for diagnosis of malignant hyperthermia. This test has a sensitivity of 99.0% but a specificity of only 93.6%. Therefore, an alternative drug is desirable which distinguishes between malignant hyperthermia-susceptible and malignant hyperthermia-normal subjects with a higher specificity and sensitivity.
  
  
  METHODS
  4-chloro-3-ethylphenol has recently been shown to trigger Ca2+-induced Ca2+-release in skeletal muscle terminal cisternae and to increase the myoplasmic free Ca2+ concentration in skeletal muscle fibres. The purpose of this study was to investigate the ability of 4-chloro-3-ethylphenol to distinguish between malignant hyperthermia-susceptible and malignant hyperthermia-normal porcine muscle specimen in the in vitro contracture test. Ten malignant hyperthermia-susceptible and 14 malignant hyperthermia-normal swine were anaesthetized and muscle biopsies were taken. For the in vitro contracture test muscle specimens were exposed to cumulative concentrations of 4-chloro-3-ethylphenol (12.5 to 200 micromol L(-1)).
  
  
  RESULTS
  4-chloro-3-ethylphenol produced contractures in a concentration-dependent manner in the malignant hyperthermia-susceptible muscle bundles. In contrast, cumulative 4-chloro-3-ethylphenol did not generate contractures in malignant hyperthermia-normal specimens. Contractures were significantly greater (P < 0.05) in the malignant hyperthermia-susceptible compared to the malignant hyperthermia-normal preparations in all 4-chloro-3-ethylphenol concentration steps from 50 micromol L(-1) to 200 micromol L(-1). There was no overlap between the two groups above a concentration of 75 micromol L(-1) in cumulative 4-chloro-3-ethylphenol in vitro contracture tests.
  
  
  CONCLUSIONS
  It remains to be verified whether an in vitro contracture test with 4-chloro-3-ethylphenol can also discriminate between malignant hyperthermia-susceptible and malignant hyperthermia-normal humans. Since no prior tested agent revealed a clear differentiation in contracture development without overlap, the 4-chloro-3-ethylphenol test might be a promising new approach to the diagnosis of malignant hyperthermia.
authors: University Hospital Hamburg-Eppendorf, Department of Anaesthesiology, Hamburg, Germany. gerbershagen@uke.uni-hamburg.de
authors: M U
authors: MU
authors: Gerbershagen
authors: F
authors: F
authors: Wappler
authors: M
authors: M
authors: Fiege
authors: R
authors: R
authors: Weilsshorn
authors: P A
authors: PA
authors: Alberts
authors: F
authors: F
authors: von Breunig
authors: J
authors: J
authors: Schulte am Esch
mesh_terms: D000818:Animals; D002733:Chlorophenols / Q000494:pharmacology*; D005260:Female; D005820:Genetic Testing; D066298:In Vitro Techniques; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis* / Q000235:genetics; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D013552:Swine
chemical_list: D002733:Chlorophenols; C091710:4-chloro-3-ethylphenol