Wang Sheng-qi, Li Chun-sheng
Emergency Department, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2010 Nov;22(11):674-9.
To investigate the effects on brain function and ultrastructure changes by elevating mean arterial pressure (MAP) with norepinephrine after cardiopulmonary resuscitation (CPR) in pigs.
After 4 minutes of untreated ventricular fibrillation, CPR was begun in 10 piglets, followed by defibrillation. Following the restoration of spontaneous circulation (ROSC), the animals were randomly assigned to two treatment groups: the hypertension group (HT, n=5), in which animals were given an infusion of norepinephrine to maintain the MAP to 130% above that before ventricular fibrillation, and the normal perfusion group (NP, n=5) who received an infusion of norepinephrine to maintain the MAP to that obtained right after ROSC. Sham-operation group of 2 animals were treated identically, with the exception that neither cardiac arrest was induced nor CPR was performed, to serve as control group. Variables of hemodynamics were measured at baseline and also 4 hours after ROSC. The overall performance categories (OPC) was evaluated 24 hours after ROSC. Then, animals were sacrificed and the brains were removed for histopathological examination of cerebral cortex, CA1 region of hippocampus, cerebellar cortex, and corpus striatum for the assay of histological damage score (HDS), and apoptosis of cerebral neurons were evaluated [terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)] 24 hours after ROSC. The ultrastructure of neurons was characterized, using transmission electron microscopy.
Five animals in the HT group showed good OPC (OPC 1-2), while 3 animals in the NP group showed good OPC (OPC 1-3). Brain tissue from different regions was normal in sham-operation group. The HDS in the cerebral cortex and CA1 region of hippocampus in the HT group was lower than that in the NP group (cerebral cortex: 1.6±0.5 vs. 2.2±0.8, hippocampus: 1.8±0.8 vs. 2.8±0.5, both P<0.05). The TUNEL- positive cells in the cerebella and the CA1 region of hippocampus were significantly reduced in the HT group compared with the NP group (cerebella:21.2±3.2 vs. 38.6±3.8, hippocampus: 22.7±7.6 vs. 35.0±6.8, both P<0.05). With transmission electron microscopy, necrotic neurons were found in the cerebral cortex, striatum and the CA1 region of hippocampus, while in cerebella only granular cells and glial cells in the CA1 region of hippocampus showed apoptosis. The damages to neurons were significantly reduced in HT group.
Hypertension induced by norepinephrine is a safe and effective method to reduce brain damages and prevent apoptosis of neurons.
探讨猪心肺复苏（CPR）后用去甲肾上腺素升高平均动脉压（MAP）对脑功能及超微结构变化的影响。
10只仔猪在未处理的室颤4分钟后开始进行CPR，随后进行除颤。自主循环恢复（ROSC）后，将动物随机分为两个治疗组：高血压组（HT，n = 5），给动物输注去甲肾上腺素以维持MAP比室颤前高130%；正常灌注组（NP，n = 5），输注去甲肾上腺素以维持MAP至ROSC刚结束时的水平。2只动物的假手术组除未诱导心脏骤停和未进行CPR外，处理方式相同，作为对照组。在基线及ROSC后4小时测量血流动力学变量。ROSC后24小时评估总体表现类别（OPC）。然后，处死动物并取出大脑，对大脑皮层、海马CA1区、小脑皮层和纹状体进行组织病理学检查以测定组织学损伤评分（HDS），并在ROSC后24小时评估脑神经元的凋亡情况[末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）]。使用透射电子显微镜对神经元的超微结构进行表征。
HT组5只动物表现出良好的OPC（OPC 1 - 2），而NP组3只动物表现出良好的OPC（OPC 1 - 3）。假手术组不同区域的脑组织正常。HT组大脑皮层和海马CA1区的HDS低于NP组（大脑皮层：1.6±0.5对2.2±0.8，海马：1.8±0.8对2.8±0.5，均P<０.０５）。与NP组相比，HT组小脑和海马CA1区的TUNEL阳性细胞明显减少（小脑：21.2±3.2对38.6±3.8，海马：22.7±7.6对35.0±6.8，均P<０.０５）。通过透射电子显微镜观察，在大脑皮层、纹状体和海马CA1区发现坏死神经元，而在小脑仅海马CA1区的颗粒细胞和胶质细胞显示凋亡。HT组对神经元的损伤明显减轻。
去甲肾上腺素诱导的高血压是一种减少脑损伤和预防神经元凋亡的安全有效方法。
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