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Delta opiates increase ischemic tolerance in isolated rabbit jejunum
Robert J Tubbs1, William A Porcaro, Won Jae Lee
1Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Summary
Delta opioid receptor (DOR) agonists, like DADLE, protect against mesenteric ischemia and reperfusion injury in rabbits. This finding suggests potential therapeutic applications for DOR agonists in non-cardiac tissues.
Area of Science:
- Physiology
- Pharmacology
- Gastroenterology
Background:
- Mammalian hibernation involves delta opioid receptor (DOR) agonists.
- DOR agonists have shown protective effects against myocardial ischemia in non-hibernating mammals.
Purpose of the Study:
- To investigate if the DOR agonist D-Ala 2, D-Leu 5, enkephalin (DADLE) protects non-cardiac mesenteric tissue from ischemia/reperfusion injury.
- To establish an in vitro model of mesenteric ischemia/reperfusion in rabbit jejunum.
Main Methods:
- Developed an in vitro rabbit jejunum model to study ischemia/reperfusion injury.
- Assessed injury based on contractile force and tissue necrosis after varying ischemic durations and oxygen/glucose deprivation.
- Evaluated the protective effect of 1 microM DADLE pretreatment before ischemia and reperfusion.
Main Results:
- Combined oxygen and glucose deprivation were necessary for significant jejunal injury.
- A direct relationship existed between ischemic duration and tissue injury.
- DADLE pretreatment significantly attenuated mesenteric ischemia/reperfusion injury, improving reperfusion contractile force (47% vs. 36% in controls).
Conclusions:
- The delta opioid agonist DADLE enhances ischemic tolerance in isolated rabbit jejunum.
- DADLE demonstrates protective effects against mesenteric ischemia/reperfusion injury.