提高平均动脉压对猪心肺复苏后脑功能及超微结构的影响

目的 探讨使用去甲肾上腺素提高平均动脉压(MAP)对心肺复苏(CPR)猪脑功能及超微结构的影响.方法 10头猪致心室纤颤(室颤)4min后行CPR及电除颤.将自主循环恢复(ROSC)的猪按随机数字表法分为两组:高灌注组5头以去甲肾上腺素升压,使MAP升至麻醉前基础状态的130%;正常灌注组5头以去甲肾上腺素维持MAP至麻醉前状态.另取2头猪作为假手术组,既不给予室颤、也不给予CPR.持续监测血流动力学指标;ROSC后24 h进行大体神经功能分类(OPC),然后处死动物取缺血敏感部位脑组织(大脑皮质、海马CA1区、小脑皮质、纹状体)进行组织缺失评分(HDS)及细胞凋亡计数[原位末端缺刻标记法(TUNEL)];同时在电镜下观察上述部位脑细胞的超微结构.结果 高灌注组5头猪均有较好的神经功能评分(OPC 1～2分);正常灌注组5头中只有3头获得较好神经功能评分(OPC 1～3分).假手术组各部位脑组织基本正常;高灌注组大脑皮质及海马CA1区HDS(分)明显好于正常灌注组(大脑:1.6±0.5比2.2±0.8,海马:1.8±0.8比2.8±0.5,均P＜0.05);小脑皮质及海马CA1区凋亡细胞(个)较正常灌注组明显减少(小脑:21.2±3.2比38.6±3.8,海马:22.7±7.6比35.0±6.8,均P＜0.05).电镜下观察,坏死神经元主要位于大脑皮质、纹状体及海马CA1区,而凋亡主要发生于小脑颗粒细胞及海马CA1区神经胶质细胞.高灌注组神经元损伤明显减轻.结论 使用去甲肾上腺素提高灌注压可以有效减轻脑损伤,并抑制脑组织细胞凋亡.

The effects on brain function and ultrastructure changes by elevating mean arterial pressure after cardiopulmonary resuscitation in pigs

Objective To investigate the effects on brain function and ultrastructure changes by elevating mean arterial pressure (MAP) with norepinephrine after cardiopulmonary resuscitation (CPR) in pigs.Methods 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.Results 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.Conclusion Hypertension induced by norepinephrine is a safe and effective method to reduce brain damages and prevent apoptosis of neurons.