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组织型纤溶酶原激活物治疗后患者和小鼠血栓的时间依赖性溶解。

Time-Dependent Thrombus Resolution After Tissue-Type Plasminogen Activator in Patients With Stroke and Mice.

机构信息

From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).

出版信息

Stroke. 2015 Jul;46(7):1877-82. doi: 10.1161/STROKEAHA.114.008247. Epub 2015 May 12.

DOI:10.1161/STROKEAHA.114.008247
PMID:25967573
Abstract

BACKGROUND AND PURPOSE

We investigated the relationship between the degree of thrombus resolution and the time from stroke onset or thrombus formation to intravenous tissue-type plasminogen activator (tPA) treatment.

METHODS

In patients with stroke, we measured thrombus volume on thin-section noncontrast brain computed tomographic scans taken at baseline and 1 hour after tPA administration. We determined the association between the time from symptom onset to tPA treatment and the degree of thrombus resolution. In a C57/BL6 mouse model of FeCl3-induced carotid artery thrombosis, we investigated the effect of tPA administered at different time intervals after thrombus formation, using Doppler-based blood flow measurement.

RESULTS

Of 249 patients enrolled, 171 showed thrombus on baseline computed tomography. Thrombus was resolved by ≥50% in 43 patients (25.1%, good volume reduction) and by <50% in 94 patients (55.0%, moderate volume reduction) 1 hour after tPA treatment. In 34 patients (19.9%, nonvolume reduction; either no change or thrombus volume increased), overall thrombus volume increased. The probability of thrombus resolution decreased as the time interval from symptom onset to treatment increased. On multivariate analysis, good volume reduction was independently related with shorter time intervals from symptom onset to tPA treatment (odds ratio, 0.986 per minute saved; 95% confidence interval, 0.974-0.999). In the mouse model, as the interval between thrombus formation and tPA treatment increased, the initiation of recanalization was delayed (P=0.006) and the frequency of final recanalization decreased (P for trends=0.006).

CONCLUSIONS

Early administration of tPA after stroke onset is associated with better thrombus resolution.

摘要

背景与目的

我们研究了从卒中发病或血栓形成到静脉给予组织型纤溶酶原激活剂(tPA)治疗的时间与血栓溶解程度之间的关系。

方法

在卒中患者中,我们在基线和 tPA 给药后 1 小时测量了薄层非对比脑 CT 扫描中的血栓体积。我们确定了从症状发作到 tPA 治疗的时间与血栓溶解程度之间的关联。在 FeCl3 诱导的颈内动脉血栓形成的 C57/BL6 小鼠模型中,我们通过基于多普勒的血流测量研究了 tPA 在血栓形成后不同时间间隔给药的效果。

结果

在纳入的 249 例患者中,171 例基线 CT 显示有血栓。在 tPA 治疗 1 小时后,43 例患者(25.1%,体积减少良好)的血栓溶解程度≥50%,94 例患者(55.0%,体积减少中度)的血栓溶解程度<50%。在 34 例患者(19.9%,体积无变化或增加)中,整体血栓体积增加。从症状发作到治疗的时间间隔越长,血栓溶解的可能性越低。多变量分析显示,体积减少良好与从症状发作到 tPA 治疗的时间间隔较短独立相关(优势比,每分钟节省 0.986;95%置信区间,0.974-0.999)。在小鼠模型中,随着血栓形成和 tPA 治疗之间的时间间隔增加,再通的开始延迟(P=0.006),最终再通的频率降低(趋势 P=0.006)。

结论

卒中发病后早期给予 tPA 与更好的血栓溶解相关。

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