title: Remifentanil preconditioning confers cardioprotection via cardiac kappa- and delta-opioid receptors.
abstract: BACKGROUND
  Remifentanil preconditioning (RPC) reduces the infarct size in anesthetized rat hearts, and this effect seems to be mediated by all three types of opioid receptors (ORs). Because there is evidence of only kappa- and delta- but not mu-ORs in the rat heart, the authors investigated whether RPC confers cardioprotection via cardiac kappa- and delta-OR as well as via extracardiac mu-OR agonist activity. The authors also investigated the involvement of signaling mechanisms, namely protein kinase C and mitochondrial adenosine triphosphate-sensitive potassium (KATP) channels.
  
  
  METHODS
  The hearts of male Sprague-Dawley rats weighing 190-210 g were removed, mounted on a Langendorff apparatus, and perfused retrogradely at 100 cm H2O with Krebs-Ringer's solution. All hearts were subjected to 30 min of ischemia and 2 h of reperfusion. The study consisted of three series of experiments on the effect of ischemic preconditioning or RPC (10, 50, and 100 ng/ml remifentanil) after blockade of OR subtypes (delta-OR antagonist naltrindol, kappa-OR antagonist nor-binaltorphimine, and mu-OR antagonist CTOP). The involvement of protein kinase C or the KATP channel in the cardioprotection of RPC was also investigated using specific blockers in each group. RPC was produced by three cycles of 5-min perfusion of remifentanil in Krebs-Ringer's solution interspersed with a 5-min reperfusion with Krebs solution only. Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining.
  
  
  RESULTS
  Infarct size as a percentage of the area at risk was significantly reduced after RPC from 51.9 +/- 5.0% (control, n = 8) to 36.2 +/- 10.0% (100 ng/ml RPC, n = 8, P < 0.01). This effect was stopped by pretreatment with naltrindol (52.3 +/- 5.2%) and nor-binaltorphimine (43.5 +/- 6.0%) but not CTOP (37.1 +/- 6.0%). Chelerythrine and GF109203X, both protein kinase C inhibitors, abolished the effects of RPC or ischemic preconditioning on infarct size as a percentage of area at risk. 5-Hydroxydecanoate (a selective mitochondrial KATP channel blocker) also abolished the cardioprotection of RPC and IPC, but HMR-1098 (a selective inhibitor of the sarcolemmal KATP channel) did not.
  
  
  CONCLUSIONS
  Cardiac delta- and kappa- but not mu-ORs mediate the cardioprotection produced by RPC. Both protein kinase C and the mitochondrial KATP channel were involved in this effect.
authors.affiliation: Department of Anaesthesiology, University of Hong Kong, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Michael G
authors.initials: MG
authors.lastname: Irwin
authors.forename: Tak Ming
authors.initials: TM
authors.lastname: Wong
authors.forename: Mai
authors.initials: M
authors.lastname: Chen
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Cao
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077208:Remifentanil
chemical_list: D002316:Cardiotonic Agents; D009292:Narcotic Antagonists; D010880:Piperidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D000077208:Remifentanil