title: Morphine postconditioning protects against reperfusion injury in the isolated rat hearts.
abstract: BACKGROUND
  Postconditioning is a novel strategy of attaining cardioprotection. Previous studies have suggested morphine mimics the effects of ischemic preconditioning. Whether it is also capable of producing postconditioning or not is still unclear. The purpose of this study was to determine (1) whether morphine postconditioning (MPostcond) would protect the heart against reperfusion injury and the subtype(s) of opioid receptors (OR) involved, (2) whether combining MPostcond with morphine preconditioning (MPC) would afford additive cardioprotection, and (3) to evaluate the role mitochondrial adenosine triphosphate-sensitive potassium (mito-K atp) channel played in MPostcond.
  
  
  METHODS
  Isolated perfused rat hearts were subjected to 45 min of ischemia followed by 1 h of reperfusion. First, three morphine concentrations (0.3, 3.0 and 30 microM) were used to study the protective effect of MPostcond. Second, the effect of blockade of OR subtypes by three antagonists (nonselective OR antagonist naloxone, kappa-OR antagonist nor-binaltorphimine, and delta-OR antagonist naltrindole) on MPostcond was investigated. Third, the protective effects of MPC, MPostcond and the combining MPC with MPostcond on reperfusion injury were compared. Last, the effect of blockade of mito-K atp by 5-hydroxydecanoate on MPostcond was studied. MPostcond was induced by a 10-min perfusion of morphine in Krebs-Ringer's solution performed at the onset of reperfusion, and MPC was produced by a 20-min perfusion of morphine 10 min before ischemia. Infarct size (IS/AAR, as a percentage of the area at risk) was determined by 2,3,5-triphenyltetrazolium staining.
  
  
  RESULTS
  IS/AAR was significantly reduced after MPostcond from 58% +/- 8% (control) to 37% +/- 6% (morphine 3.0 microM, P < 0.01). This effect was abolished by coadministering naloxone (58% +/- 7%), nor-binaltorphimine (52% +/- 5%), but not naltrindole (34% +/- 5%). MPC and MPostcond had similar extent of protective effect on IS/AAR, and combining MPC with MPostcond did not afford further cardiprotection. 5-Hydroxydecanoate also abolished the cardioprotection of MPostcond. Unexpectedly, all three OR antagonists and 5-hydroxydecanoate themselves also afforded some extent of cardioprotection.
  
  
  CONCLUSIONS
  MPost confers cardioprotection via activating kappa-OR but not delta-OR and opening mito-K atp channels. MPost and MPC have no additive protection. kappa-OR and mito-K atp channel may play a dual role in protecting ischemia-reperfusion injury.
authors.affiliation: Department of Anesthesiology, Affiliated Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China.
authors.forename: Zuolei
authors.initials: Z
authors.lastname: Chen
authors.forename: Tianzuo
authors.initials: T
authors.lastname: Li
authors.forename: Bingxi
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D000701:Analgesics, Opioid; D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D009292:Narcotic Antagonists; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C052853:5-hydroxydecanoic acid; D009020:Morphine