Abstract | UNLABELLED: 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.
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Authors | Robert J Tubbs, William A Porcaro, Won Jae Lee, David J Blehar, Robert E Carraway, Karin Przyklenk, Eric W Dickson |
Journal | Academic emergency medicine : official journal of the Society for Academic Emergency Medicine
(Acad Emerg Med)
Vol. 9
Issue 6
Pg. 555-60
(Jun 2002)
ISSN: 1069-6563 [Print] United States |
PMID | 12045067
(Publication Type: Journal Article)
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Chemical References |
- Receptors, Opioid, delta
- Enkephalin, Leucine-2-Alanine
- Glucose
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Topics |
- Animals
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Enkephalin, Leucine-2-Alanine
(pharmacology)
- Glucose
(deficiency)
- Hypoxia
(physiopathology, prevention & control)
- In Vitro Techniques
- Ischemia
(physiopathology, prevention & control)
- Jejunum
(blood supply, drug effects)
- Muscle Contraction
(physiology)
- Muscle, Smooth
(physiopathology)
- Rabbits
- Receptors, Opioid, delta
(agonists)
- Reperfusion Injury
(physiopathology, prevention & control)
- Splanchnic Circulation
(drug effects)
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