enkephalin--leucine-2-alanine and Ischemia

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.. To determine whether the DOR agonist D-Ala 2, D-Leu 5, enkephalin (DADLE) similarly elicits protection in noncardiac-i.e., mesenteric-tissue.. 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).. 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).. Treatment with the delta opioid agonist DADLE increases ischemic tolerance of isolated rabbit jejunum.

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

Topics: Adult; Coronary Disease; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Extremities; Humans; Ischemia; Male; Microcirculation; Middle Aged; Sympatholytics