title: Cardioprotection from remote preconditioning involves spinal opioid receptor activation.
abstract: OBJECTIVE
  Remote preconditioning is a powerful and potentially clinically viable mode of cardioprotection. The mechanisms underlying its transmission process have not been extensively studied. The aim of this study was to test the hypothesis that spinal opioid receptors are involved with signal transmission of remote cardiac preconditioning.
  
  
  METHODS
  Two established models of remote preconditioning were used, one using intermittent ischaemia of the lower limb (remote ischaemic preconditioning, RIPC) and the other by stimulation of cutaneous pain fibres via an abdominal incision (remote preconditioning of trauma, RPOT). Classic ischaemic preconditioning (IPC) was used as positive control. Selective blockade of spinal opioid receptors was achieved through intrathecal injection of naloxone methiodide, a compound not known to cross the blood-brain barrier.
  
  
  RESULTS
  The prior introduction of naloxone methiodide abolished the cardioprotective effects of RIPC, RPOT but not IPC, as assessed by infarct size as a percentage of area at risk following 30min of ischaemia and 120min reperfusion. Of the specific receptor antagonists, only that specific for the mu receptor subtype, and not delta or kappa receptor, block the protective response.
  
  
  CONCLUSIONS
  These results suggest that the central nervous system at the spinal cord level is involved with the relaying of signals between the afferent and efferent arms of remote preconditioning.
authors.affiliation: Department of Anaesthesiology, University of Hong Kong, Hong Kong SAR, China. gordon@hku.hk
authors.forename: Gordon Tin Chun
authors.initials: GT
authors.lastname: Wong
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.forename: Bin
authors.initials: B
authors.lastname: Mei
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.forename: Michael G
authors.initials: MG
authors.lastname: Irwin
mesh_terms: D000818:Animals; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D011957:Receptors, Opioid; D009270:Naloxone; C041269:N-methylnaloxone