Hemorrhagic transformation is related to the duration of occlusion and treatment with tissue plasminogen activator in a nonembolic stroke model
Hemorrhagic transformation is related to the duration of occlusion and treatment with tissue plasminogen activator in a nonembolic stroke model
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DOI：
10.1179/016164103101201526
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发表时间：
2003-06-01
影响因子：
1.9
通讯作者：
Knight, RA
中科院分区：
文献类型：
--
作者：
Fagan, SC;Nagaraja, TN;Knight, RA
急性缺血性卒中患者的再灌注治疗的可用性使得出血性转化的原因和意义成为一个备受关注和争议的领域。92只雄性Wistar大鼠进行短暂的大脑中动脉闭塞（MCAO）1和6小时之间。40只动物接受10 mg/kg重组组织型纤溶酶原激活剂（rtPA），在再灌注前5 min开始输注20 min。在18-24小时，处死动物。记录染色切片上出血性转化（HT）的存在，并使用图像分析软件定量总缺血性病变面积。对17只动物（11只HT）进行免疫组织化学分析，以检测内皮屏障抗原（EBA），在3个切片中定量，每个切片8个不同的区域。卡方分析和逻辑回归用于评估rtPA和闭塞持续时间对HT发展的贡献。进行嵌套重复测量方差分析，以评估缺血引起的EBA变化和HT相关性。59只动物发生HT，与闭塞时间（p < 0.0001）和缺血性病变大小（p = 0.0007）显著相关。rtPA的存在加速了HT的发展。在有HT（p < 0.001）和无HT（p <0.001）的动物的纹状体（梗死核心）中发现了EBA存在的统计学显著的侧对侧差异，但仅在闭塞持续时间为2小时或更长的动物中。在大鼠短暂性MCAO中，闭塞持续时间是HT的重要预测因素，并且与EBA表达密切相关。
The availability of reperfusion therapy for acute ischemic stroke patients has made the causes and significance of hemorrhagic transformation an area of intense interest and controversy. Ninety-two male Wistar rats underwent transient middle cerebral artery occlusion (MCAO) of between 1 and 6 h. Forty animals received 10 mg kg(-1) of recombinant tissue plasminogen activator (rtPA), infused over 20 min, starting 5 min before reperfusion. At 18-24 h, the animals were sacrificed. The presence of hemorrhagic transformation (HT) on stained sections was recorded and total ischemic lesion area was quantified using image analysis software. Seventeen animals (11 with HT) were subjected to immunohistochemical analysis for detection of endothelial barrier antigen (EBA), quantified in three sections, in eight different fields per section. Chi-squared analysis and logistic regression were used to assess the contribution of rtPA and duration of occlusion to HT development. Nested, repeated measures analyses of variance were performed to assess the changes in EBA caused by ischemia and associated with HT. Fifty-nine animals developed HT that was significantly associated with occlusion duration (p < 0.0001) and ischemic lesion size (p = 0.0007). The presence of rtPA accelerated HT development. Statistically significant side-to-side differences in the presence of EBA were found in the striatum (core of the infarct) of animals with HT (p < 0.001) and without HT (p < 0.001), but only in animals with durations of occlusion of 2 h or more. Duration of occlusion is an important predictor of HT in transient MCAO in the rat and is closely associated with EBA expression.