The Role of Opioid Receptor Antagonists on Acute Mesenteric Small Bowel Ischemia in the Rat: The Comparative Effects of (-)-Naloxone and Nalmefene
Williamson, Malcolm E. II
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The effects of two opioid receptor antagonists, (-)-naloxone and nalmefene, were studied on acute mesenteric small bowel ischemia in the rat. In previous studies, (-)-naloxone has been shown to increase the survival rate of animals experiencing such an injury. It is thought that through some mechanism, (-)naloxone impedes the neutrophilic production and/or cytotoxicity of oxygen free radicals. Such cytotoxic radicals have been found to be mediators of ischemia / reperfusion injury. without these radicals, the ischemia / reperfusion injury should be attenuated and survivability increased. It was the purpose of this experiment to determine the comparative effects of (-)-naloxone and nalmefene on small bowel ischemia / reperfusion injury. (-)Naloxone and nalmefene were administered to Sprague-Dawley rats in varying dosages after 75 min. of mesenteric ischemia. The animals' survival rates and lactate dehydrogenase levels were then observed over a period of 72 hrs. The highest survival rates among drug tested animals occurred at low dosages while larger doses, 100 µg of drug/kg of rat mass, revealed no changes in survival rate compared to the control. At a dosage of 10 µg/kg, both nalmefene and (-)-naloxone tested animals had survival rates more than twice that of the control. However, similar results between (-)-naloxone and nalmefene were not observed at every dose. Therefore, even though both drugs attenuate ischemia / reperfusion injury, it remains uncertain as to whether they both have equal effects.