Fleischer J E, Tateishi A, Drummond J C, Scheller M S, Grafe M R, Zornow M H, Shearman G T, Shapiro H M
Department of Anesthesiology, University of California, San Diego, La Jolla 92093.
J Cereb Blood Flow Metab. 1989 Dec;9(6):795-804. doi: 10.1038/jcbfm.1989.113.
The excitatory amino antagonist MK-801 was administered to cats following resuscitation from cardiac arrest to evaluate its effect on neurologic and neuropathologic outcome in a clinically relevant model of complete cerebral ischemia. In 29 cats studied, cardiac arrest (ventricular fibrillation) was maintained for 18 min and resuscitation was successfully performed in 21 cats. Four animals underwent a sham arrest. MK-801 or placebo was administered in a blinded, randomized manner. Beginning at 5 min post resuscitation (PR), MK-801 330 micrograms/kg over 2 min followed by 73 micrograms/kg/h for 10 h or the same volume of placebo was administered. Resuscitated animals remained paralyzed and sedated in an intensive care setting for 24-30 h PR. Neurologic examinations were performed at 2, 4, and 7 days PR by observers blinded to the treatment groups. Seventeen cats were entered into data analysis (nine MK-801-treated and eight placebo-treated). MK-801-treated animals had a significantly greater neurologic deficit score (NDS) rank (0 = normal, 100 = brain death) 2 days PR (mean rank 12.1 vs. 5.6; p = 0.008). This difference is most likely due to ongoing sedative actions of MK-801. There were no significant differences in NDS rank at 4 (10.3, MK-801 vs. 7.5, placebo) and 7 (9.6, MK-801 vs. 8.3, placebo) days PR. There were no significant differences in frontal cortex, hippocampus, occipital cortex, or cerebellar neuropathology between groups. Sham-arrested cats had normal neurologic and neuropathologic evaluations. In the circumstance of complete cerebral ischemia as employed in the current study, MK-801 had no beneficial effect upon neurologic or neuropathologic outcome.
在猫经历心脏骤停复苏后，给予兴奋性氨基酸拮抗剂MK - 801，以评估其在完全性脑缺血的临床相关模型中对神经和神经病理学结果的影响。在研究的29只猫中，心脏骤停（室颤）持续18分钟，21只猫成功复苏。4只动物进行了假骤停。MK - 801或安慰剂以盲法、随机方式给药。从复苏后（PR）5分钟开始，在2分钟内给予MK - 801 330微克/千克，随后以73微克/千克/小时的速度给药10小时，或给予相同体积的安慰剂。复苏后的动物在重症监护环境中保持瘫痪和镇静状态24 - 30小时PR。由对治疗组不知情的观察者在PR后2天、4天和7天进行神经学检查。17只猫进入数据分析（9只接受MK - 801治疗，8只接受安慰剂治疗）。接受MK - 801治疗的动物在PR后2天的神经功能缺损评分（NDS）等级（0 = 正常，100 = 脑死亡）明显更高（平均等级12.1对5.6；p = 0.008）。这种差异很可能是由于MK - 801持续的镇静作用。在PR后4天（MK - 801为10.3，安慰剂为7.5）和7天（MK - 801为9.6，安慰剂为8.3），NDS等级没有显著差异。两组之间额叶皮质、海马体、枕叶皮质或小脑的神经病理学没有显著差异。假骤停的猫神经学和神经病理学评估正常。在本研究采用的完全性脑缺血情况下，MK - 801对神经或神经病理学结果没有有益影响。
