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尽管有超声溶栓,但颈动脉的溶栓再通高度依赖于狭窄程度。

Thrombolytic Recanalization of Carotid Arteries Is Highly Dependent on Degree of Stenosis, Despite Sonothrombolysis.

作者信息

Tomkins Amelia J, Hood Rebecca J, Pepperall Debbie, Null Christopher L, Levi Christopher R, Spratt Neil J

机构信息

School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia Hunter Medical Research Institute, New Lambton, NSW, Australia.

Seventh Wave Laboratories, Chesterfield, MO.

出版信息

J Am Heart Assoc. 2016 Feb 23;5(2):e002716. doi: 10.1161/JAHA.115.002716.

Abstract

BACKGROUND

Stroke associated with acute carotid occlusion is associated with poor effectiveness of tissue plasminogen activator (tPA) thrombolysis and poor prognosis. Rupture of atherosclerotic plaques resulting in vascular occlusions may occur on plaques, causing variable stenosis. We hypothesized that degree of stenosis may affect recanalization rates with tPA. Ultrasound+tPA (sonothrombolysis) has been shown to improve recanalization for intracranial occlusions but has not been tested for carotid occlusion. Our primary aim was to determine thrombolytic recanalization rates in a model of occlusion with variable stenosis, with a secondary aim to investigate sonothrombolysis in this model.

METHODS AND RESULTS

Rat carotid arteries were crushed and focal stenosis created (25% baseline Doppler flow) with a silk-suture tie invoking thrombosis and occlusion. To model mild or severe stenosis, the tie was released pretreatment or left in place. Animals were treated with tPA (10 mg/kg) or tPA+ultrasound (2-MHz) in each stenosis model (n=7/group). Recanalization was assessed by Doppler flow. Thrombolytic recanalization rates were significantly higher in mild stenosis groups (71% versus 0% with severe stenosis; P<0.0001). Recanalization rates were not significantly higher with additional ultrasound in either model.

CONCLUSIONS

In this model, the degree of carotid stenosis had a large effect on thrombolytic recanalization. Sonothrombolysis using standard parameters for intracranial sonothrombolysis did not increase recanalization. Further testing is warranted. The degree of underlying stenosis may be an important predictor of thrombolytic recanalization, and clinical correlation of these findings may provide new approaches to treatment selection for patients with carotid occlusion.

摘要

背景

与急性颈动脉闭塞相关的中风与组织型纤溶酶原激活剂(tPA)溶栓效果不佳及预后不良有关。动脉粥样硬化斑块破裂导致血管闭塞可能发生在斑块上,造成不同程度的狭窄。我们推测狭窄程度可能影响tPA的再通率。超声联合tPA(超声溶栓)已被证明可提高颅内闭塞的再通率,但尚未在颈动脉闭塞中进行测试。我们的主要目的是确定在具有不同狭窄程度的闭塞模型中的溶栓再通率,次要目的是研究该模型中的超声溶栓。

方法与结果

将大鼠颈动脉压碎,用丝线结扎造成局灶性狭窄(基线多普勒血流的25%),引发血栓形成和闭塞。为模拟轻度或重度狭窄,在预处理时松开结扎或保留结扎。在每个狭窄模型中,动物接受tPA(10mg/kg)或tPA+超声(2MHz)治疗(每组n=7)。通过多普勒血流评估再通情况。轻度狭窄组的溶栓再通率显著更高(轻度狭窄组为71%,重度狭窄组为0%;P<0.0001)。在任一模型中,额外使用超声并未使再通率显著提高。

结论

在该模型中,颈动脉狭窄程度对溶栓再通有很大影响。使用颅内超声溶栓标准参数的超声溶栓并未增加再通率。有必要进行进一步测试。潜在狭窄程度可能是溶栓再通的重要预测指标,这些发现的临床相关性可能为颈动脉闭塞患者的治疗选择提供新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1403/4802445/e9294accdc49/JAH3-5-e002716-g001.jpg

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