Delta opiates increase ischemic tolerance in isolated rabbit jejunum
Department of Emergency Medicine; Department of Anesthesiology
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
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine
Tubbs, Robert J.; Porcaro, William A.; Lee, Won Jae; Blehar, David J.; Carraway, Robert E.; Przyklenk, Karin; and Dickson, Eric W., "Delta opiates increase ischemic tolerance in isolated rabbit jejunum" (2002). University of Massachusetts Medical School. Senior Scholars Program. Paper 173.