Delta opiates increase ischemic tolerance in isolated rabbit jejunum.

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.

• 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)

Chemical References

• Receptors, Opioid, delta
• Enkephalin, Leucine-2-Alanine
• Glucose

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)