title: Controlled hyperkalemic reperfusion with magnesium rescues ischemic juvenile hearts by reducing calcium loading.
abstract: OBJECTIVE
  Our objectives were (1) to determine whether elevated Mg(2+) in controlled hyperkalemic reperfusate without intervention during ischemia protects the juvenile heart against reperfusion injury; and (2) to identify the mechanism(s) underlying any protective effect of Mg(2+).
  
  
  METHODS
  Langendorff-perfused hearts from juvenile (11- to 14-day-old) guinea pigs were subjected to mild (30-minute) or severe (45-minute) normothermic global ischemia and 35-minute reperfusion. Hearts were subjected to controlled hyperkalemic reperfusion without or with various concentrations of Mg(2+) (5, 10, 16, 23 mM). The mechanisms underlying the effect of Mg(2+) on intracellular Ca(2+) ([Ca(2+)]i) were also studied in isolated cardiomyocytes exposed to metabolic inhibition followed by washout using hyperkalemic solutions (reperfusion).
  
  
  RESULTS
  Sixteen mM Mg(2+) conferred maximal cardioprotection as assessed by improved functional recovery and reduced cardiac injury; this was associated with a significant recovery of cardiac energetics and metabolism following both mild and severe ischemia. The Mg(2+)-induced protection was additive to that of hyperkalemia following mild ischemia and conferred protection following severe ischemia when hyperkalemia alone had no significant effect. Elevated Mg(2+) in the hyperkalemic reperfusate of cardiomyocytes acutely prevented [Ca(2+)]i loading following mild metabolic inhibition and augmented the fall in [Ca(2+)]i following severe metabolic inhibition.
  
  
  CONCLUSIONS
  This work demonstrates for the first time in juvenile hearts that elevated Mg(2+) during controlled hyperkalemic reperfusion rescues the heart following ischemia, and that this is likely to be facilitated by reducing [Ca(2+)]i which, in turn, would aid metabolic recovery.
authors.affiliation: Department of Surgery 2, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Imura
authors.forename: Hua
authors.initials: H
authors.lastname: Lin
authors.forename: Elinor J
authors.initials: EJ
authors.lastname: Griffiths
authors.forename: M-Saadeh
authors.initials: MS
authors.lastname: Suleiman
mesh_terms: D000367:Age Factors; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004734:Energy Metabolism / Q000187:drug effects; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006947:Hyperkalemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015636:Magnesium Chloride / Q000008:administration & dosage*; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010477:Perfusion / Q000379:methods*; D011189:Potassium Chloride / Q000008:administration & dosage*; D020127:Recovery of Function; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D015636:Magnesium Chloride; D011189:Potassium Chloride