The Efficacy of Opioid Antagonists Against Heatstroke-Induced Ischemia and Injury in Rats

Prior administration of naltrexone or cyclic d-phe-cys-try-arg-thr-pen-thr-NH,2 (CTAP) (a μ-opioid receptor antagonist), but not nor-binaltorphine (a K-opioid receptor antagonist) or ICI-174864 (a δ-opioid receptor antagonist), improve heat tolerance in the rat. As compared to those of normothermic controls, all vehicle-pretreated heatstroke rats displayed higher levels of creatinine, blood urea nitrogen, alkaline phosphatase, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, tumor necrosis factor-alpha, prothrombin time, activated partial thromboplastin time, and d-dimer in the plasma, cellular ischemia and injury markers in brain, and intracranial pressure. In contrast, all vehicle pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, brain PO2, and platelet count and protein C in the plasma. Twenty minutes before the start of heat exposure, prior administration of CTAP or naltrexone improves heat tolerance by reducing the systemic inflammation, hyper-coagulable state, and tissue ischemia and injury that occurred during heatstroke. The results show that μ-opioid receptor antagonism is effective for attenuation of heatstroke reactions.

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