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在胶原酶诱导的大鼠脑出血模型中,达比加群是否会增加迟发性血肿扩大的风险?

Does dabigatran increase the risk of delayed hematoma expansion in a rat model of collagenase-induced intracerebral hemorrhage?

作者信息

Tanoue Shunsuke, Inamasu Joji, Yamada Masayuki, Toyama Hiroshi, Hirose Yuichi

机构信息

Department of Neurosurgery, Fujita Health University School of Medicine, Toyoake, Japan; Department of Neurosurgery, Self-Defense Forces Central Hospital, Tokyo, Japan.

Department of Neurosurgery, Fujita Health University School of Medicine, Toyoake, Japan.

出版信息

J Stroke Cerebrovasc Dis. 2015 Feb;24(2):374-80. doi: 10.1016/j.jstrokecerebrovasdis.2014.09.010. Epub 2014 Nov 25.

Abstract

BACKGROUND

Delayed hematoma expansion is common in intracerebral hemorrhage (ICH) patients using warfarin. Dabigatran induces fewer hemorrhagic complications compared with warfarin. However, the natural history of dabigatran-related ICH remains unclear. This study aims to clarify whether dabigatran increases the risk of delayed hematoma expansion in a rat ICH model.

METHODS

Male Wistar rats were treated with 2 dosages of dabigatran etexilate (DE: 10 mg/kg, n = 4; 20 mg/kg, n = 3) 30 minutes before ICH induction using intraparenchymal collagenase infusion. Five rats that received saline were used as controls. Magnetic resonance imaging was performed 24 and 48 hours after ICH induction, and serial hematoma volume measurements were obtained using T2-weighted images. Expanded hematoma volumes were calculated by subtracting hematoma volumes at 48 hours from those at 24 hours; the hematoma expansion rate was defined as the ratio of the expanded hematoma volume to that at 24 hours.

RESULTS

The mean hematoma volumes (mm(3)) at 24 hours were 13.3 ± 3.3 in the control group, 14.9 ± 2.0 in the 10 mg/kg DE group, and 18.9 ± 7.6 in the 20 mg/kg DE group with no significant intergroup differences (P = .26). The mean hematoma volumes at 48 hours (mm(3)) were 21.7 ± 4.9 in the control group, 22.1 ± 5.0 in the 10 mg/kg DE group, and 23.4 ± 5.8 in the 20 mg/kg DE group with no significant intergroup differences (P = .90). Consequently, there were no significant intergroup differences in the hematoma expansion rates (P = .33).

CONCLUSIONS

This experimental study of a rat ICH model indicates that dabigatran-related ICH may not increase the risk of delayed hematoma expansion.

摘要

背景

在使用华法林的脑出血(ICH)患者中,血肿延迟扩大很常见。与华法林相比,达比加群引起的出血并发症较少。然而,达比加群相关ICH的自然病程仍不清楚。本研究旨在阐明达比加群是否会增加大鼠ICH模型中血肿延迟扩大的风险。

方法

雄性Wistar大鼠在通过脑实质内注入胶原酶诱导ICH前30分钟,接受2种剂量的达比加群酯(DE:10mg/kg,n = 4;20mg/kg,n = 3)治疗。5只接受生理盐水的大鼠作为对照。在ICH诱导后24小时和48小时进行磁共振成像,并使用T2加权图像获得系列血肿体积测量值。通过从24小时时的血肿体积中减去48小时时的血肿体积来计算扩大的血肿体积;血肿扩大率定义为扩大的血肿体积与24小时时血肿体积的比值。

结果

对照组24小时时的平均血肿体积(mm³)为13.3±3.3,10mg/kg DE组为14.9±2.0,20mg/kg DE组为18.9±7.6,组间差异无统计学意义(P = 0.26)。对照组48小时时的平均血肿体积(mm³)为21.7±4.9,10mg/kg DE组为22.1±5.0,20mg/kg DE组为23.4±5.8,组间差异无统计学意义(P = 0.90)。因此,血肿扩大率组间差异无统计学意义(P = 0.33)。

结论

这项大鼠ICH模型的实验研究表明,达比加群相关ICH可能不会增加血肿延迟扩大的风险。

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