title: Cardioprotective effects of hyperkalemia during simulated ischemia/reperfusion in neonatal rat cardiomyocytes-Preservation of Na(+)/K(+)-ATPase activity-.
abstract: BACKGROUND
  Hyperkalemia has multimodal effects on myocardial protection during ischemia/reperfusion. The preservation of Na(+)/K(+)-ATPase activity induced by hyperkalemia may have critical impact on myocardial protection.
  
  
  METHODS
  To elucidate the roles of hyperkalemia (16 mM) and Na(+)/K(+)-ATPase inhibition (100 µM ouabain) in myocardial protection during simulated ischemia (5 mM NaCN and 5.5 mM 2-deoxyglucose)/reperfusion, we measured loss of membrane integrity and bleb formation using a vital dye calcein AM in cultured neonatal rat cardiomyocytes. The control perfusate was switched to treatment solution for 15 min, followed by reperfusion for 30 min. In a second set of experiments, myocardial excitability and diastolic intracellular calcium ion concentration ([Ca(2+)]i) were measured during a 45-min treatment using a calcium-sensitive fluorescent dye fluo-4 AM.
  
  
  RESULTS
  Simulated ischemia/reperfusion under ouabain treatment induced loss of membrane integrity, which was suppressed by hyperkalemia. Simulated ischemia/reperfusion induced bleb formation, which was accelerated by ouabain. Hyperkalemia delayed and inhibited the increase in diastolic [Ca(2+)]i induced by simulated ischemia. Furthermore, hyperkalemia almost completely inhibited the effects of ouabain on the diastolic [Ca(2+)]i during ischemia.
  
  
  CONCLUSIONS
  These results suggest that hyperkalemia during ischemia is cardioprotective against ischemia/reperfusion insults and that hyperkalemia inhibits the effects of ouabain during ischemia.
authors.affiliation: Department of Anesthesiology, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Takata
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shuzo
authors.initials: S
authors.lastname: Oshita
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006947:Hyperkalemia / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
chemical_list: D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium