Delta opiates increase ischemic tolerance in isolated rabbit jejunum

UMMS Affiliation

Department of Emergency Medicine; Department of Anesthesiology

Publication Date


Document Type



Animals; Anoxia; Disease Models, Animal; Dose-Response Relationship, Drug; Enkephalin, Leucine-2-Alanine; Glucose; In Vitro Techniques; Ischemia; Jejunum; Muscle Contraction; Muscle, Smooth; Rabbits; Receptors, Opioid, delta; Reperfusion Injury; Splanchnic Circulation


Anesthesiology | Emergency Medicine


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.

DOI of Published Version



Acad Emerg Med. 2002 Jun;9(6):555-60. DOI: 10.1197/aemj.9.6.555 Link to article on publisher's site

Journal/Book/Conference Title

Academic emergency medicine : official journal of the Society for Academic Emergency Medicine


Medical students Robert J. Tubbs and William A. Porcaro participated in this study as part of the Senior Scholars research program at the University of Massachusetts Medical School.

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Link to Article in PubMed

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