title: Diazoxide provides protection to human myocardium in vitro that is concentration dependent.
abstract: BACKGROUND
  Diazoxide has been shown to confer significant myocardial protection in many experiments. This study was designed to assess its influence on the structural injury and functional recovery of human myocardium subjected to hypoxia/reoxygenation in vitro.
  
  
  METHODS
  The isolated electrically driven human right atrial trabeculae, obtained during cardiac surgery, were studied. The tissue bath was oxygenated with 95% oxygen and 5% carbon dioxide, hypoxia being obtained by replacing oxygen with argon. The influence of diazoxide on atrial contractility was studied first. Next, the two trabeculae from one atrial appendage were studied simultaneously, adding diazoxide to the tissue bath 10 minutes before hypoxia in one, with another serving as a control. We tested 10(-4.5) mol/L and 10(-4) mol/L diazoxide in three sets of experiments testing 30, 60, and 90 minutes of hypoxia. We continued reoxygenation for 120 minutes (in 60-minute and 90-minute hypoxia experiments) and subsequently tested reaction to 10(-4) mol/L norepinephrine. Apart from continuous recording of the contraction force, we measured the troponin I release into the tissue bath after ischemia and reoxygenation.
  
  
  RESULTS
  Diazoxide exerted a negative inotropic effect in human atrial muscle (pD(2)=3.96 +/- 0.18). Both concentrations of diazoxide studied resulted in better functional recovery of atrial trabeculae subjected to 30 minutes of hypoxia. With longer hypoxia, only the higher diazoxide concentration provided significant protection as assessed by contractility. After 120 minutes of reoxygenation, only diazoxide-treated muscle was viable enough to respond to norepinephrine. Only 10(-4) mol/L diazoxide resulted in lower troponin I release during hypoxia and reoxygenation.
  
  
  CONCLUSIONS
  This study shows that diazoxide provides significant concentration-dependent protection against hypoxia/reoxygenation injury to human myocardium in vitro.
authors.affiliation: Second Department of Cardiac Surgery, Katowice, Poland. narizol@slam.katowice.pl
authors.forename: Marek A
authors.initials: MA
authors.lastname: Deja
authors.forename: Krzysztof S
authors.initials: KS
authors.lastname: Golba
authors.forename: Maciej
authors.initials: M
authors.lastname: Kolowca
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Widenka
authors.forename: Jolanta
authors.initials: J
authors.lastname: Biernat
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Wos
mesh_terms: D015687:Cell Hypoxia / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D009206:Myocardium
chemical_list: D003981:Diazoxide