Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain.
J Thromb Haemost. 2010 Jul;8(7):1567-74. doi: 10.1111/j.1538-7836.2010.03897.x. Epub 2010 Apr 30.
Growth factors (GF) such as vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and granulocyte-colony stimulating factor (G-CSF) have been associated with greater efficacy of tissue plasminogen activator (tPA) in experimental studies.
To study the association of these GF with arterial recanalization and clinical outcome in patients with acute ischemic stroke treated with tPA.
We prospectively studied 79 patients with ischemic stroke attributable to MCA occlusion treated with i.v. tPA within the first 3 h from onset of symptoms. Continuous transcranial color-coded sonography (TCCS) was performed during the first 2 h after tPA bolus to assess early MCA recanalization. Hemorrhagic transformation (HT) was classified according to ECASS II definitions. Good functional outcome was defined as a Rankin scale score of 0-2 at 90 days. GF levels were determined by ELISA.
Mean serum levels of VEGF, G-CSF and Ang-1 at baseline were significantly higher in patients with early MCA recanalization (n = 30) (all P < 0.0001). In the multivariate analysis, serum levels of VEGF (OR, 1.03), G-CSF (OR, 1.02) and Ang-1 (OR, 1.07) were independently associated with early MCA recanalization (all P < 0.0001). On the other hand, patients with parenchymal hematoma (PH) (n = 20) showed higher levels of Ang-1 (P < 0.0001). Ang-1 (OR, 1.12; P < 0.0001) was independently associated with PH, whereas patients with good outcome (n = 38) had higher levels of G-CSF (P < 0.0001). G-CSF was independently associated with good outcome (OR, 1.12; P = 0.036).
These findings suggest that GF may enhance arterial recanalization in patients with ischemic stroke treated with t-PA, although they might increase the HT.
血管内皮生长因子(VEGF)、血管生成素-1(Ang-1)和粒细胞集落刺激因子(G-CSF)等生长因子与组织型纤溶酶原激活物(tPA)在实验研究中的更大疗效有关。
研究这些生长因子与接受 tPA 治疗的急性缺血性脑卒中患者的动脉再通和临床结局的关系。
我们前瞻性研究了 79 例由 MCA 闭塞引起的缺血性脑卒中患者,这些患者在症状发作后 3 小时内接受了静脉内 tPA 治疗。在 tPA 推注后最初 2 小时内连续进行经颅彩色编码超声(TCCS)检查,以评估早期 MCA 再通情况。根据 ECASS II 定义对出血转化(HT)进行分类。90 天时良好的功能结局定义为 Rankin 量表评分为 0-2 分。通过 ELISA 测定生长因子水平。
早期 MCA 再通的患者(n=30)基线时 VEGF、G-CSF 和 Ang-1 的血清水平显著升高(均 P<0.0001)。多变量分析显示,VEGF(OR,1.03)、G-CSF(OR,1.02)和 Ang-1(OR,1.07)的血清水平与早期 MCA 再通独立相关(均 P<0.0001)。另一方面,有实质血肿(PH)的患者(n=20)显示出更高的 Ang-1 水平(P<0.0001)。Ang-1(OR,1.12;P<0.0001)与 PH 独立相关,而有良好结局的患者(n=38)具有更高的 G-CSF 水平(P<0.0001)。G-CSF 与良好结局独立相关(OR,1.12;P=0.036)。
这些发现表明,生长因子可能增强接受 t-PA 治疗的缺血性脑卒中患者的动脉再通,但它们可能会增加 HT。