Hoffman W E, Kochs E, Werner C, Thomas C, Albrecht R F
Department of Anesthesiology, Michael Reese Hospital, University of Illinois, Chicago 60616.
Anesthesiology. 1991 Aug;75(2):328-32. doi: 10.1097/00000542-199108000-00022.
Dexmedetomidine is an alpha 2-adrenergic agonist that decreases central sympathetic activity and reduces the anesthetic requirement for halothane. We evaluated the effect of dexmedetomidine on neurologic and histopathologic outcome from incomplete cerebral ischemia in the rat. Anesthesia was maintained with a 25-micrograms.kg-1.h-1 fentanyl infusion combined with 70% nitrous oxide. Incomplete ischemia was produced by unilateral carotid artery ligation combined with hemorrhagic hypotension to 35 mmHg for 30 min. Arterial blood gas tensions, pH, and head temperature were maintained at normal levels during the experiment. Four ischemic groups were tested: group 1 (n = 15) received an intraperitoneal (ip) saline injection (control); group 2 (n = 10) received an ip injection of 10 micrograms/kg dexmedetomidine 30 min before ischemia; group 3 (n = 10) received 100 micrograms/kg dexmedetomidine; and group 4 (n = 10) received 100 micrograms/kg dexmedetomidine plus 1 mg/kg atipamezole (an alpha 2-adrenergic antagonist). Neurologic outcome was evaluated for 3 days using a graded deficit score. Histopathology was evaluated in coronal section in caudate and hippocampal tissue segments. Dexmedetomidine (10 and 100 micrograms/kg) significantly decreased plasma catecholamines and improved neurologic and histopathologic outcome in a dose-dependent manner compared to control rats (P less than 0.05). Atipamezole abolished the decrease in catecholamines and the improvement in outcome seen with dexmedetomidine, confirming that these effects were mediated by alpha 2-adrenergic receptors. It is concluded that alpha 2-adrenoreceptor stimulation decreases sympathetic activity and decreases ischemic injury in a model of incomplete cerebral ischemia.
右美托咪定是一种α2肾上腺素能激动剂，可降低中枢交感神经活性并减少氟烷的麻醉需求。我们评估了右美托咪定对大鼠不完全性脑缺血后神经功能和组织病理学结果的影响。通过持续输注25微克·千克-1·小时-1的芬太尼并联合70%氧化亚氮维持麻醉。通过单侧颈动脉结扎并将出血性低血压维持在35 mmHg 30分钟来产生不完全性缺血。实验过程中动脉血气张力、pH值和头部温度维持在正常水平。测试了四个缺血组：第1组（n = 15）接受腹腔内（ip）生理盐水注射（对照）；第2组（n = 10）在缺血前30分钟接受10微克/千克右美托咪定的ip注射；第3组（n = 10）接受100微克/千克右美托咪定；第4组（n = 10）接受100微克/千克右美托咪定加1毫克/千克阿替美唑（一种α2肾上腺素能拮抗剂）。使用分级缺陷评分评估3天的神经功能结果。在尾状核和海马组织切片的冠状切片中评估组织病理学。与对照大鼠相比，右美托咪定（10和100微克/千克）显著降低血浆儿茶酚胺，并以剂量依赖方式改善神经功能和组织病理学结果（P < 0.05）。阿替美唑消除了右美托咪定引起的儿茶酚胺降低和结果改善，证实这些作用是由α2肾上腺素能受体介导的。得出结论，在不完全性脑缺血模型中，α2肾上腺素能受体刺激可降低交感神经活性并减少缺血性损伤。
