title: Effects of theophylline on anesthetized malignant hyperthermia-susceptible pigs.
abstract: BACKGROUND
  Theophylline was shown to induce contracture development in porcine malignant hyperthermia (MH) susceptible (MHS) skeletal muscles in vitro. The purpose of the current study was to investigate the in vivo effects of theophylline in MHS and MH normal (MHN) swine.
  
  
  METHODS
  MH-trigger-free general anesthesia was performed in MHS and MHN swine. Theophylline was administered intravenously in cumulative doses up to 93.5 mg·kg⁻¹. The clinical occurrence of MH was defined by changes of central-venous pCO₂, central-venous pH, and body core temperature.
  
  
  RESULTS
  Theophylline induced comparable clinical alterations in the anesthetized MHS and MHN swine, especially in regard to hemodynamic data. No pig developed hypermetabolism and/or MH according to defined criteria. All animals died with tachycardia followed by ventricular fibrillation.
  
  
  CONCLUSIONS
  The cumulative theophylline doses used in this study were much higher than doses used therapeutically in humans, as demonstrated by measured blood concentrations. Theophylline is thus not a trigger of MH in genetically determined swine.
authors: Department of Anesthesiology, Hospital Itzehoe, Robert-Koch-Straβe 2, 25524 Itzehoe, Germany. m.fiege@kh-itzehoe.de
authors: Marko
authors: M
authors: Fiege
authors: Ralf
authors: R
authors: Weisshorn
authors: Kerstin
authors: K
authors: Kolodzie
authors: Frank
authors: F
authors: Wappler
authors: Mark U
authors: MU
authors: Gerbershagen
mesh_terms: D000758:Anesthesia / Q000009:adverse effects; D018685:Anesthetics, Inhalation / Q000009:adverse effects; D000818:Animals; D001784:Blood Gas Analysis; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics; D006801:Humans; D008305:Malignant Hyperthermia / Q000209:etiology / Q000503:physiopathology*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013552:Swine; D013806:Theophylline / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D010726:Phosphodiesterase Inhibitors; D013806:Theophylline; D002118:Calcium