NEUROPROTECTION BY THE ALPHA-2-ADRENOCEPTOR AGONIST DEXMEDETOMIDINE IN A FOCAL MODEL OF CEREBRAL-ISCHEMIA
NEUROPROTECTION BY THE ALPHA-2-ADRENOCEPTOR AGONIST DEXMEDETOMIDINE IN A FOCAL MODEL OF CEREBRAL-ISCHEMIA
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DOI：
10.1097/00000542-199308000-00016
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发表时间：
1993-08-01
期刊：
影响因子：
8.8
通讯作者：
MAZE, M
中科院分区：
文献类型：
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作者：
MAIER, C;STEINBERG, GK;MAZE, M
背景右美托咪定是一种高选择性α 2-肾上腺素受体激动剂，可降低中枢交感神经活性并减少氟烷的麻醉需求。初步研究表明，右美托咪定改善缺血性injury的结果，因此，可能具有潜在的治疗value.Methods：作者研究了14只家兔，进行了2小时闭塞的左颈内动脉，大脑前动脉，大脑中动脉，然后4小时的再灌注。闭塞后10分钟，使用计算的计算机控制输注速率用生理盐水（n = 7）或右美托咪定（n = 7）处理动物，以维持稳态血浆浓度。右美托咪定给药动物的氟烷浓度降低50%，以维持相当的麻醉水平。体感诱发电位用于确认充分缺血，并通过组织病理学评估损伤。皮质缺血性神经元损伤面积各组间差异有统计学意义（氟烷单独给药，38.2 +/- 6.0% SEM vs.氟烷加右美托咪定，20.0 +/- 2.7% SEM，P = 0.018），但不在纹状体中（氟烷单独给药，68.7 +/- 12.6% SEM vs氟烷加右美托咪定，43.5 +/- 15.9% SEM，P = 0.24），生理参数也无变化。右美托咪定血浆水平每90分钟获得的平均值为4.0 +/- 0.15 ng/ml.Conclusions：从这项研究的结果表明，缺血后给药的右美托咪定，在剂量，减少麻醉剂的需求由50%，在局灶性脑缺血模型具有神经保护作用。
Background. Dexmedetomidine, a highly selective alpha2-adrenoreceptor agonist, decreases central sympathetic activity and reduces the anesthetic requirement of halothane. Preliminary studies show that dexmedetomidine improves the outcome from ischemic injury and, therefore, may have potential therapeutic value.Methods: The authors studied 14 rabbits that underwent a 2-h occlusion of the left internal carotid, anterior cerebral, and middle cerebral arteries, followed by 4 h of reperfusion. Ten minutes after occlusion, the animals were treated with either normal saline (n = 7) or dexmedetomidine (n = 7) using a computer-controlled infusion rate calculated to maintain a steady state plasma concentration. Halothane concentration was reduced by 50% for dexmedetomidine-treated animals to maintain a comparable level of anesthesia. Somatosensory evoked potentials were used to confirm adequate ischemia, and injury was assessed by histopathology.Results: There were significant differences in the area of ischemic neuronal damage between the groups in the cortex (halothane alone, 38.2 +/- 6.0% SEM vs. halothane plus dexmedetomidine, 20.0 +/- 2.7% SEM, P = 0.018), but not in the striatum (halothane alone, 68.7 +/- 12.6% SEM vs. halothane plus dexmedetomidine, 43.5 +/- 15.9% SEM, P = 0.24), nor in physiologic parameters. Dexmedetomidine plasma levels obtained every 90 min showed a mean of 4.0 +/- 0.15 ng/ml.Conclusions: Results from this study indicate that postischemic administration of dexmedetomidine, in a dose that reduces the anesthetic requirements by 50%, has a neuroprotective effect in this model of focal cerebral ischemia.