Remifentanil post-conditioning attenuates cardiac ischemia-reperfusion injury via kappa or delta opioid receptor activation.
BACKGROUND
Ischemic pre- or post-conditioning of the heart has been shown to involve opioid receptors. Remifentanil, an ultra-short-acting selective mu opioid receptor agonist in clinical use, pre-conditions the rat heart against ischemia-reperfusion injury. This study investigates whether remifentanil post-conditioning is also cardioprotective.


METHODS
Remifentanil post-conditioning (5-min infusion at 1, 5, 10 or 20 microg/kg/min) or ischemic post-conditioning (three cycles of a 10 s reperfusion interspersed with a 10 s ischemia) was induced in an open-chest rat heart model of ischemia and reperfusion injury, in the presence or absence of nor-binaltorphimine, naltrindole or CTOP, specific kappa, delta and mu opioid receptor antagonists, respectively. The same sequence of experiments was repeated in the isolated heart model using the maximal protective dose of remifentanil from the dose-response studies.


RESULTS
Both ischemic and remifentanil post-conditioning reduced the myocardial infarct size relative to the control group in both models. This cardioprotective effect for both post-conditioning regimes was prevented by the prior administration of nor-binaltorphimine and naltrindole but not CTOP. The sole administration of the antagonists had no effect on the size of myocardial infarction.


CONCLUSIONS
These results indicate that remifentanil post-conditioning protects the heart from ischemia-reperfusion injury to a similar extent as of ischemic post-conditioning. This protection involves kappa and delta but not mu opioid receptor activation. This drug has great potential as a clinical post-conditioning modality as it can be given in large doses without prolonged opioid-related side effects.
Wong
G T C
GT
Department of Anaesthesiology, University of Hong Kong, Queen Mary Hospital, Hong Kong. gordon@hkucc.hku.hk
Li
R
R
Jiang
L L
LL
Irwin
M G
MG
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D000077208:Remifentanil; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D000701:Analgesics, Opioid; D002316:Cardiotonic Agents; D009292:Narcotic Antagonists; D010880:Piperidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C051844:norbinaltorphimine; D013004:Somatostatin; D009271:Naltrexone; C055382:naltrindole; D000077208:Remifentanil