title: Role of Endogenous Opioid System in Ischemic-Induced Late Preconditioning.
abstract: BACKGROUND
  Opioid receptors (OR) are involved in myocardial late preconditioning (LPC) induced by morphine and δ1-opioid receptor (δ1-OR) agonists. The role of OR in ischemic-induced LPC is unknown. We investigated whether 1) OR are involved in the trigger and/or mediation phase of LPC and 2) a time course effect on the expression of different opioid receptors and their endogenous ligands exists.
  
  
  METHODS
  Male Wistar rats were randomly allocated to four groups (each group n = 8). Awake animals were ischemic preconditioned by a 5 minutes coronary occlusion. 24 hours later, anesthetized animals underwent 25 minutes coronary occlusion followed by 2 hours of reperfusion. The role of OR was investigated by treatment with intraperitoneal naloxone (Nal) 10 minutes prior to LPC (Nal-LPC; trigger phase) or 10 min prior to sustained ischemia (LPC-Nal; mediation phase).
  
  
  RESULTS
  LPC reduced infarct size from 61±10% in controls to 25±9% (P<0.001). Naloxone during trigger or mediation phase completely abolished LPC-induced cardioprotection (59±9% and 62±9%; P<0.001 vs. LPC). 8, 12 and 24 hours after the ischemic stimulus, expression of δ-OR in the heart was increased, whereas μ-opioid receptor (μ-OR) and κ-opioid receptor (κ-OR) were not. Plasma concentrations of β-endorphin and leu-enkephalin but not dynorphin were increased by LPC.
  
  
  CONCLUSIONS
  Ischemic LPC is triggererd and mediated by OR. Expression of δ-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC.
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany; Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Fraessdorf
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Hanschmann
authors.affiliation: Department of Cardiovasacular Physiology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Heinen
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nina C
authors.initials: NC
authors.lastname: Weber
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany.
authors.forename: Ragnar
authors.initials: R
authors.lastname: Huhn
mesh_terms: D000818:Animals; D019194:Ischemic Preconditioning; D008297:Male; D018847:Opioid Peptides / Q000097:blood / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018847:Opioid Peptides