Widmayer M A, Turner T D, Browning J L, Baskin D S
Department of Surgery, Veteran's Affairs Medical Center, Houston, TX.
Mol Chem Neuropathol. 1994 Aug;22(3):211-23. doi: 10.1007/BF03160107.
Many pharmacotherapies for stroke that have been successful in the laboratory have proven to be ineffective in the clinical setting, often because patients do not arrive for treatment until hours after the onset of the ischemic insult. Kappa opioid treatment of cerebral ischemia has been successful in the cat and mouse with treatment delays of up to 6 h. The purpose of the present study was to develop a model of delayed kappa opioid treatment of cerebral ischemia in the rabbit. Fourteen rabbits underwent permanent, unilateral occlusion of the internal carotid, middle cerebral, and anterior cerebral arteries via a transorbital, microsurgical approach. At 6 h postocclusion, animals received a blinded bolus injection and continuous infusion of either saline or the kappa agonist, U50488. Survival was not improved after U50488 treatment. U50488 treatment did, however, reduce areas of severe tissue damage and increase areas of modest tissue damage. This suggests U50488 arrested the progression of damage from noninfarcted to fully infarcted tissue. The present results show beneficial effects of delayed treatment with kappa agonists in a species similar in vasculature to humans, and much less costly than primates or cats.
许多在实验室中取得成功的中风药物疗法在临床环境中却被证明是无效的，这通常是因为患者直到缺血性损伤发作数小时后才开始接受治疗。在猫和小鼠中，κ阿片类药物治疗脑缺血在治疗延迟长达6小时的情况下取得了成功。本研究的目的是建立兔脑缺血延迟κ阿片类药物治疗的模型。十四只兔子通过经眶显微手术方法进行永久性单侧颈内动脉、大脑中动脉和大脑前动脉闭塞。在闭塞后6小时，动物接受盲法推注注射，并持续输注生理盐水或κ激动剂U50488。U50488治疗后存活率没有提高。然而，U50488治疗确实减少了严重组织损伤区域，并增加了轻度组织损伤区域。这表明U50488阻止了从非梗死组织到完全梗死组织的损伤进展。目前的结果表明，在血管系统与人类相似的物种中，κ激动剂延迟治疗具有有益效果，而且比灵长类动物或猫的成本低得多。
