Effect of Tirilazad Mesylate on Middle Cerebral Artery Occlusion/Reperfusion in Nonhuman Primates
Effect of Tirilazad Mesylate on Middle Cerebral Artery Occlusion/Reperfusion in Nonhuman Primates
复制标题
甲磺酸替拉扎德对非人灵长类动物大脑中动脉闭塞/再灌注的影响
DOI：
10.1159/000107880
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发表时间：
1995
影响因子：
2.9
通讯作者：
G. Zoppo
中科院分区：
文献类型：
--
作者：
E. Mori;J. Ember;B. Copeland;W. Thomas;J. Koziol;G. Zoppo
具有脂质膜保护特性的药物在理论上可以减少局灶性脑缺血早期脑动脉再通过程中的缺血损伤区域。在一项设盲、随机安慰剂对照研究中，在清醒狒狒模型中，检查了假定的脂质过氧化抑制剂甲磺酸替拉扎德（U 74006 F）对大脑中动脉闭塞3小时后和随后再灌注后梗死体积和神经学结局的影响。清醒的受试者（各8名）被随机分配接受甲磺酸替拉扎德（3 mg/kg）或匹配的车辆给予再灌注前15分钟，并再次在2，4，12和24小时后再灌注。根据定量量表对神经系统状态进行连续评估，并在14天时对灌注固定标本计算梗死体积。在替拉扎德组中观察到平均总梗死体积指数降低40%，基底节体积标准化。与安慰剂相比，替拉扎德输注组的平均神经系统评分的持续改善和增加。对多形核白细胞反应的平行研究表明，多形核白细胞反应性无显著变化。在再灌注前但局灶性脑缺血发作后给予甲磺酸替拉扎德，观察到梗死体积减少，主要是皮质/皮质下白色物质，神经学结局改善。
Agents with lipid membrane protective properties may theoretically reduce the zone of ischemic damage during cerebral arterial recanalization in the early hours of focal cerebral ischemia. The effect of the putative lipid peroxidation inhibitor tirilazad mesylate (U74006F) on infarction volume and neurological outcome following 3-hour middle cerebral artery occlusion and subsequent reperfusion in an awake baboon model was examined in a blinded, randomized placebo-controlled study. Awake subjects (8 each) were assigned randomly to receive either tirilazad mesylate (3 mg/kg) or matched vehicle given 15 min prior to reperfusion, and again at 2, 4, 12, and 24 h after reperfusion. Neurological status was serially assessed according to a quantitative scale and infarction volumes were computed on perfusion-fixed specimens at 14 days. A 40% reduction in mean total infarction volume index, normalized for basal ganglia volume, was seen in the tirilazad group. Persistent and increased improvement in mean neurological score with tirilazad infusion paralleled that of the placebo. Parallel studies on polymorphonuclear leukocyte responses indicated no significant changes in polymorphonuclear leukocyte reactivity. A reduction in infarction volume, predominantly in the cortex/subcortical white matter, and an improvement in neurological outcome were observed when tirilazad mesylate was given prior to reperfusion, but after the onset of focal cerebral ischemia.