title: Opioid receptor agonist Eribis peptide 94 reduces infarct size in different porcine models for myocardial ischaemia and reperfusion.
abstract: Eribis peptide 94 (EP 94) is a novel enkephalin analog, thought to interact with the μ- and δ-opioid receptors. The purpose of the present study was to examine the cardioprotective potential of EP 94 in two clinically relevant porcine models of myocardial ischaemia and reperfusion, and to investigate if such an effect is associated with an increased expression of endothelial nitric oxide synthase (eNOS). Forty-one anesthetized pigs underwent 40min of coronary occlusion followed by 4h of reperfusion. In Protocol I, balloon occlusion of the left anterior descending artery was performed with concurrent intravenous administration of (A) vehicle (n=7), (B) EP 94 (1ug/kg) after 5, 12, 19 and 26min of ischaemia (n=4) or (C) EP 94 (1ug/kg) after 26, 33, 40min of ischaemia (n=6). In Protocol II, open-chest pigs were administered (D) vehicle (n=6) or (E) 0.2ug/kg/min of EP 94 (n=6) through an intracoronary infusion into the jeopardized myocardium, started after 30min of ischaemia and maintained for 15min. The hearts were stained and the protein content of eNOS measured. EP 94 reduces infarct size when administered both early and late during ischaemia compared with vehicle (infarct size group A 61.6±2%, group B 50.2±3% and group C 49.2±2%, respectively, P<0.05), as well as when infused intracoronary (infarct size group D 82.2±3.9% and group E 61.2±2.5% respectively, P<0.01). Phosphorylated eNOS Ser(1177) in relation to total eNOS was significantly increased in the group administered EP 94, indicating activation of nitric oxide production.
authors.affiliation: Department of Molecular and Clinical Medicine, University of Gothenburg, SE-413 45 Gothenburg, Sweden. lars.o.karlsson@vgregion.se
authors.forename: Lars O
authors.initials: LO
authors.lastname: Karlsson
authors.forename: Lars
authors.initials: L
authors.lastname: Grip
authors.forename: Erik
authors.initials: E
authors.lastname: Bissessar
authors.forename: Irina
authors.initials: I
authors.lastname: Bobrova
authors.forename: Thomas
authors.initials: T
authors.lastname: Gustafsson
authors.forename: Mohammad
authors.initials: M
authors.lastname: Kavianipour
authors.forename: Jacob
authors.initials: J
authors.lastname: Odenstedt
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wikström
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Gonon
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011957:Receptors, Opioid / Q000819:agonists*; D013552:Swine
chemical_list: D002316:Cardiotonic Agents; D004745:Enkephalins; D018847:Opioid Peptides; D011957:Receptors, Opioid; C557293:eribis peptide 94; D052250:Nitric Oxide Synthase Type III