Fentanyl reduces infarction but not stunning via delta-opioid receptors and protein kinase C in rats.
Langendorff rat hearts were used (i) to examine whether fentanyl reduces stunning, infarction or both, and (ii) to investigate if this protection is mediated by delta-opioid receptors and/or protein kinase C (PKC). In the stunning study, hearts were subjected to global ischaemia (20 min) and reperfusion. This did not produce infarction. Postischaemic mechanical function was measured in hearts treated with or without fentanyl (740 nM). Fentanyl did not affect postischaemic mechanical function. In the infarction study, the left anterior descending coronary artery was occluded for 35 min and infarct size was assessed by triphenyltetrazolium chloride staining. Hearts in the control group exhibited an infarct zone/area at risk (I/R) of 39 (SEM 5)%, whereas the I/R for the fentanyl group was 13 (2)%. When the hearts were treated with a delta-opioid receptor antagonist (naltrindole 1 nM) or a PKC inhibitor (chelerythrine 2 microM), the effect of fentanyl was abolished, with I/R of 37 (1) and 36 (2)% respectively. In our model, we conclude that fentanyl protects against infarction but not against stunning, and that the limitation of ischaemic injury is mediated by both delta-opioid receptors and PKC.
Kato
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Nuffield Department of Anaesthetics, Radcliffe Infirmary, Oxford, UK.
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D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D004396:Coloring Agents; D005283:Fentanyl / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000517:prevention & control; D017682:Myocardial Stunning / Q000188:drug therapy / Q000517:prevention & control; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000187:drug effects*
D000701:Analgesics, Opioid; D004396:Coloring Agents; D017465:Receptors, Opioid, delta; D011493:Protein Kinase C; D005283:Fentanyl