Delta opiates increase ischemic tolerance in isolated rabbit jejunum

Acad Emerg Med. 2002 Jun;9(6):555-60. doi: 10.1111/j.1553-2712.2002.tb02291.x.

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.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enkephalin, Leucine-2-Alanine / pharmacology*
  • Glucose / deficiency
  • Hypoxia / physiopathology
  • Hypoxia / prevention & control
  • In Vitro Techniques
  • Ischemia / physiopathology
  • Ischemia / prevention & control*
  • Jejunum / blood supply*
  • Jejunum / drug effects*
  • Muscle Contraction / physiology
  • Muscle, Smooth / physiopathology
  • Rabbits
  • Receptors, Opioid, delta / agonists*
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Splanchnic Circulation / drug effects

Substances

  • Receptors, Opioid, delta
  • Enkephalin, Leucine-2-Alanine
  • Glucose