title: Dose-dependent cardioprotection of enkephalin analogue Eribis peptide 94 and cardiac expression of opioid receptors in a porcine model of ischaemia and reperfusion.
abstract: Opioids confer cardioprotection after myocardial ischaemia and reperfusion. The primary aim of the present study was to evaluate the cardioprotective effect of different doses of enkephalin analogue Eribis peptide 94 (EP 94) in a porcine model of ischaemia and reperfusion. A secondary aim was to analyse the impact of ischaemia and reperfusion on the expression of opioid receptor subtypes in the porcine heart. Thirty-four anesthetised pigs underwent 40 min of balloon occlusion of the left anterior descending coronary artery followed by four hours of reperfusion. Pigs were given either vehicle (0.9% NaCl) or one of four doses of EP 94 (0.2, 1, 5 or 25 ug/kg at each administration, respectively), intravenously after 26, 33 and 40 min of ischaemia. Hearts were stained to quantify area at risk and infarct size. mRNA and protein expressions of the opioid receptor subtypes were detected with RT-PCR, immunoblotting and immunohistochemistry in the control and ischaemic/reperfused areas. There was a significant dose-response relationship between higher doses of EP 94 and reduced infarct size. Expression of κ- and δ-opioid receptors was detected at both mRNA and protein levels. In ischaemic/reperfused areas, an increased expression of mRNA for both receptors was observed, whereas only protein expression for the δ subtype was up-regulated. The μ-opioid receptor was not detected.
authors: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Göteborg, Sweden. lars.o.karlsson@vgregion.se
authors: Lars O
authors: LO
authors: Karlsson
authors: Niklas
authors: N
authors: Bergh
authors: Lizhen
authors: L
authors: Li
authors: Erik
authors: E
authors: Bissessar
authors: Irina
authors: I
authors: Bobrova
authors: Garrett J
authors: GJ
authors: Gross
authors: Levent M
authors: LM
authors: Akyürek
authors: Lars
authors: L
authors: Grip
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy; D002316:Cardiotonic Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism*; D012306:Risk; D013552:Swine
chemical_list: D002316:Cardiotonic Agents; D004745:Enkephalins; D012333:RNA, Messenger; D011957:Receptors, Opioid; C557293:eribis peptide 94