title: Delta opiates increase ischemic tolerance in isolated rabbit jejunum.
abstract: Mammalian hibernation is mediated by humoral agonists of the delta opioid receptor (DOR). Moreover, transfer of either humoral or synthetic DOR agonists to non-hibernators reportedly induces a state of improved myocardial ischemic tolerance.
  
  
  OBJECTIVE
  To determine whether the DOR agonist D-Ala 2, D-Leu 5, enkephalin (DADLE) similarly elicits protection in noncardiac-i.e., mesenteric-tissue.
  
  
  METHODS
  In Protocols 1 and 2, the authors developed and characterized an in vitro model of mesenteric ischemia/reperfusion in isolated rabbit jejunum by documenting the effect of increasing ischemic duration (0 to 120 minutes) and the relative importance of glucose and/or oxygen deprivation on the evolution of jejunal injury. In Protocol 3, jejunal segments were randomized to receive either no treatment (controls) or 15 minutes of pretreatment with 1 microM DADLE, followed by 60 minutes of simulated ischemia and 30 minutes of reperfusion. Jejunal injury was quantified by repeated, time-matched assessment of peak contractile force evoked by 1 microM acetylcholine (all protocols) and delineation of tissue necrosis (Protocol 1).
  
  
  RESULTS
  Development of significant jejunal injury required combined oxygen/glucose deprivation. Moreover, there was a direct relationship between ischemic duration and tissue injury, and a significant inverse correlation between reperfusion contractile force (% of baseline) and the extent of smooth muscle necrosis (r(2) = 0.87; p < 0.01). Most notably, mesenteric ischemia/reperfusion injury was attenuated by DADLE: reperfusion contractile force was 47 +/- 5% versus 36 +/- 5% in DADLE-treated versus control segments (p < 0.01).
  
  
  CONCLUSIONS
  Treatment with the delta opioid agonist DADLE increases ischemic tolerance of isolated rabbit jejunum.
authors.affiliation: Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tubbs
authors.forename: William A
authors.initials: WA
authors.lastname: Porcaro
authors.forename: Won Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: David J
authors.initials: DJ
authors.lastname: Blehar
authors.forename: Robert E
authors.initials: RE
authors.lastname: Carraway
authors.forename: Karin
authors.initials: K
authors.lastname: Przyklenk
authors.forename: Eric W
authors.initials: EW
authors.lastname: Dickson
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000503:physiopathology / Q000517:prevention & control; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D007583:Jejunum / Q000098:blood supply* / Q000187:drug effects*; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000503:physiopathology; D011817:Rabbits; D017465:Receptors, Opioid, delta / Q000819:agonists*; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013152:Splanchnic Circulation / Q000187:drug effects
chemical_list: D017465:Receptors, Opioid, delta; D016308:Enkephalin, Leucine-2-Alanine; D005947:Glucose