Roles of δ-opioid receptor in the cardioprotective effects of fentanyl postconditioning and remote ischemic postconditioning against rat myocardial ischemia/reperfusion injury in vivo

Abstract

Objective To investigate the roles of δ-opioid receptor in the cardioprotective effects by fentanyl postconditioning and limb remote ischemia postconditioning (RIPOC). Methods Myocardial ischemia/reperfusion injury (IRI)model was established by ligation of the left anterior descending coronary artery (LAD) for 30 min and then reperfusion for 180 min.Seventy-two rats were randomly divided into four groups,which received fentanyl (30 μg/kg),RIPOC,combined fentanyl and RIPOC,or saline only (placebo)at 15 min after LAD ligation.Animals of each group were further divided into the subgroup A which received saline only 5 min before LAD ligation and subgroup B which received the δ-opioid antagonist naltrindole (NTD,5 mg/kg).At the end of reperfusion,level of creatine kinase isoenzyme MB (CK-MB) in plasma and serum activity of cardiac troponin I (cTnI)were measured,and infarct size (IS％ value) was determined by 2,3,5 -triphenyltetrazolium chloride staining. Results The IS％values of subgroups C-A,F-A,R-A,F-R-A,C-B,F-B,R-B,and F-R-B were (59.6±3.1),(55.6±2.2),(48.4±1.4),(35.5±1.7),(57.9 ±2.0),(52.2±2.4),(50.3 ± 1.2)％ and (46.9 ±2.8)％,respectively.Both fentanyl postconditioning and RIPOC significantly decreased the IS％ value,CK-MB and cTnI level induced by IRI,and these effects were enhanced as fentanyl postconditioning plus RIPOC.Effect of fentanyl postconditioning but not RIPOC against IRI,was attenuated by NTD.Also,synergistic effect between the fentanyl postconditioning and RIPOC on infarct size sparing disappeared when pretreated with NTD.Conclusions The δ-opioid receptor was involved in the cardioprotection of fentanyl postconditioning,but not in RIPOC,and it plays an important role in the synergistic effect in combination with the fentanyl PPOC and RIPOC. Key words: Myocardial ischemia/reperfusion injury;  Cardioprotection;  Remote ischemia postconditioning; Pharmacological postconditioning;  Opioid receptor