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Delta Opiates Increase Ischemic Tolerance in Isolated Rabbit Jejunum
Author(s) -
Tubbs Robert J.,
Porcaro William A.,
Lee Won Jae,
Blehar David J.,
Carraway Robert E.,
Przyklenk Karin,
Dickson Eric W.
Publication year - 2002
Publication title -
academic emergency medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.221
H-Index - 124
eISSN - 1553-2712
pISSN - 1069-6563
DOI - 10.1197/aemj.9.6.555
Subject(s) - dadle , medicine , agonist , ischemia , anesthesia , reperfusion injury , jejunum , endocrinology , opioid receptor , receptor
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 μM 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 μM 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.