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预测实验成功:采用大鼠肠内丝线模型的回顾性病例对照研究。

Predicting experimental success: a retrospective case-control study using the rat intraluminal thread model of stroke.

机构信息

Department of Anesthesiology, University Hospital Aachen, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, D-52074 Aachen, Germany.

3CARE, Cardiovascular Critical Care & Anesthesia Research, University Hospital Aachen, RWTH Aachen University, D-52047 Aachen, Germany.

出版信息

Dis Model Mech. 2020 Dec 29;13(12):dmm044651. doi: 10.1242/dmm.044651.

Abstract

The poor translational success rate of preclinical stroke research may partly be due to inaccurate modelling of the disease. We provide data on transient middle cerebral artery occlusion (tMCAO) experiments, including detailed intraoperative monitoring to elaborate predictors indicating experimental success (ischemia without occurrence of confounding pathologies). The tMCAO monitoring data (bilateral cerebral blood flow, CBF; heart rate, HR; and mean arterial pressure, MAP) of 16 animals with an 'ideal' outcome (MCA-ischemia), and 48 animals with additional or other pathologies (subdural haematoma or subarachnoid haemorrhage), were checked for their prognostic performance (receiver operating characteristic curve and area under the curve, AUC). Animals showing a decrease in the contralateral CBF at the time of MCA occlusion suffered from unintended pathologies. Implementation of baseline MAP, in addition to baseline HR (AUC, 0.83, 95% c.i. 0.68 to 0.97), increased prognostic relevance (AUC, 0.89, 95% c.i. 0.79 to 0.98). Prediction performance improved when two additional predictors referring to differences in left and right CBF were considered (AUC, 1.00, 95% c.i. 1.0 to 1.0). Our data underline the importance of peri-interventional monitoring to verify a successful experimental performance in order to ensure a disease model as homogeneous as possible.

摘要

临床前卒中研究的低转化成功率可能部分归因于疾病模型的不准确。我们提供了短暂性大脑中动脉闭塞(tMCAO)实验的数据,包括详细的术中监测,以阐述表明实验成功的预测指标(缺血而没有发生混杂性病变)。16 只具有“理想”结果(MCA 缺血)的动物和 48 只具有其他或其他病变(硬膜下血肿或蛛网膜下腔出血)的动物的 tMCAO 监测数据(双侧脑血流,CBF;心率,HR;和平均动脉压,MAP),检查了其预后性能(接收者操作特征曲线和曲线下面积,AUC)。在 MCA 闭塞时出现对侧 CBF 下降的动物发生了意外病变。除了基线 HR(AUC,0.83,95%置信区间 0.68 至 0.97)之外,还实施了基线 MAP 的实施,增加了预后相关性(AUC,0.89,95%置信区间 0.79 至 0.98)。当考虑两个额外的参考左、右 CBF 差异的预测指标时,预测性能得到了改善(AUC,1.00,95%置信区间 1.0 至 1.0)。我们的数据强调了在介入期间监测的重要性,以验证实验性能的成功,以确保疾病模型尽可能同质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64cf/7790196/6fc149d9af13/dmm-13-044651-g1.jpg

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