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Delta opiates increase ischemic tolerance in isolated rabbit jejunum
Authors
Tubbs, Robert J.Porcaro, William A.
Lee, Won Jae
Blehar, David J.
Carraway, Robert E.
Przyklenk, Karin
Dickson, Eric W.
Document Type
Journal ArticlePublication Date
2002-06-01Keywords
AnimalsAnoxia
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
Metadata
Show full item recordAbstract
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.Source
Acad Emerg Med. 2002 Jun;9(6):555-60. DOI: 10.1197/aemj.9.6.555 Link to article on publisher's siteDOI
10.1197/aemj.9.6.555Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49231PubMed ID
12045067Notes
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.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1197/aemj.9.6.555