An improved survival model of hypoxia/ischaemia in the piglet suitable for neuroprotection studies

An improved survival model of hypoxia/ischaemia in the piglet suitable for neuroprotection studies
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DOI:
10.1016/s0006-8993(01)03011-6
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发表时间:
2001-11-16
期刊:
影响因子:
2.9
通讯作者:
Roberts, MS
Roberts, MS
中科院分区:
医学3区
文献类型:
--
作者:
Foster, KA;Colditz, PB;Roberts, MS

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本研究的目的是开发一种缺氧/缺血的新生仔猪模型,该模型将更好地模拟窒息的人类新生儿的临床情况,并在损伤后产生一致程度的组织病理学损伤。用丙泊酚(10 mg/kg/h)和阿芬太尼(5,5.5 μ g/kg/h)静脉注射混合物麻醉1日龄仔猪(n = 18)。对仔猪进行插管和通气。连续监测生理变量。通过将吸入氧(FiO(2))降低至3-4%并调节FiO(2)以维持脑功能监测峰值振幅小于或等于5 μ V来诱导缺氧。轻度损伤的持续时间为20分钟,而重度损伤为30分钟,其中包括10分钟,其中允许血压降至基线的70%以下。对照仔猪(n=4/18)进行相同的方案,除了缺氧/缺血损伤。使仔猪从麻醉中恢复,然后在损伤后72小时处以安乐死。将脑灌注固定,取出并包埋在石蜡中。冠状切片用苏木精/伊红染色。一名不知情的观察者检查了额叶和顶叶皮质、海马、基底神经节、丘脑和小脑的损伤程度。严重损伤的脑的五个区域的总平均组织学评分为15.6 +/-4.4(平均值+/-S.D.,n=7),而在轻度损伤(n=4)或对照组中均未观察到损伤。这种“严重损伤”模型产生了一致的损伤水平,并将证明对检查新生儿大脑中潜在的神经保护疗法有用。(C)2001年,爱思唯尔科学。All rights reserved.
The purpose of this study, was to develop a newborn piglet model of hypoxia/ischaemia which would better emulate the clinical situation in the asphyxiated human neonate and produce a consistent degree of histopathological injury following the insult. One-day-old piglets (n = 18) were anaesthetised with a mixture of propofol (10 mg/kg/h) and alfentinal (5,5.5 mug/kg/h) i.v. The piglets were intubated and ventilated. Physiological variables were monitored continuously. Hypoxia was induced by decreasing the inspired oxygen (FiO(2)) to 3-4% and adjusting FiO(2) to maintain the cerebral function monitor peak amplitude at less than or equal to5 muV. The duration of the mild insult was 20, min while the severe insult was 30 min which included 10 min where the blood pressure was allowed to fall below 70% of baseline. Control piglets (n=4 of 18) were subjected to the same protocol except for the hypoxic/ischaemic insult. The piglets were allowed to recover from anaesthesia then euthanased 72 It after the insult. The brains were perfusion-fixed, removed and embedded in paraffin. Coronal sections were stained by haematoxylin/eosin. A blinded observer examined the frontal and parietal cortex, hippocampus, basal ganglia, thalamus and cerebellum for the degree of damage. The total mean histology score for the five areas of the brain for the severe insult was 15.6 +/-4.4 (mean +/-S.D., n=7), whereas no damage was seen in either the mild insult (n=4) or control groups. This 'severe damage' model produces a consistent level of damage and will prove useful for examining potential neuroprotective therapies in the neonatal brain. (C) 2001 Elsevier Science BY. All rights reserved.