Background and purpose

In this study we tested the effect of antiangiogenics on a swine angiogenesis model that shares some brain AVM histological characteristics. The objective was to determine bevacizumab effects on retia volumes and on vessels’ wall.

Materials and methods

Fifteen pigs were divided into 3 groups: Five animals served as controls (group A), 5 animals underwent endovascular left external and common carotid artery occlusion (group B) and 5 animals underwent the same procedure and had an intra-arterial in-situ injection of bevacizumab (group C) 2 months after the occlusion. A DSA associated with 3D-rotational angiography was performed at day 0 and at 3 months in all groups in order to measure rete mirabile volumes. The animals were sacrificed at 3 months and the retia were harvested for pathological and immunohistochemistry examinations.

Results

All VEGF-A receptors were blocked at the site of injection and there was a local enhanced endothelial proliferation and apoptosis. The volume of the retia remained unchanged after the bevacizumab injection. Retia vessels presented comparable media thickness, higher endothelial proliferation and apoptosis after the anti-VEGF injection.

Conclusion

A single in-situ injection of bevacizumab in this swine angiogenesis model showed no change in retia volume and an extensive blockage of VEGF receptors at the site of injection one month later. Rete mirabile vessels presented comparable media thickness, higher endothelial proliferation and apoptosis after the anti-VEGF injection, suggesting that bevacizumab antiangiogenic effect does not fragilize vessel wall. More studies are needed to confirm these preliminary insights of in-situ antiangiogenic effect on vascular malformations.

中文翻译：

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动脉内原位贝伐单抗注射对血管生成的影响。猪血管生成模型的结果

背景和目的

在这项研究中，我们测试了抗血管生成剂对具有某些脑 AVM 组织学特征的猪血管生成模型的影响。目的是确定贝伐单抗对视网膜体积和血管壁的影响。

材料和方法

15头猪分为3组：5只动物作为对照组（A组），5只动物进行左颈外动脉和颈总动脉血管内闭塞（B组），5只动物进行相同的程序并进行动脉内原位注射 闭塞后 2 个月使用贝伐单抗（C组）。在第 0 天和第 3 个月时，所有组都进行了与 3D 旋转血管造影相关的 DSA，以测量视网膜容量。在第 3 个月处死动物并收获视网膜用于病理学和免疫组织化学检查。

结果

所有VEGF-A受体在注射部位均被阻断，局部内皮增殖和凋亡增强。注射贝伐单抗后视网膜的体积保持不变。在注射抗 VEGF 后，视网膜血管呈现出相当的介质厚度、更高的内皮增殖和凋亡。

结论

在该猪血管生成模型中单次原位注射贝伐单抗显示视网膜体积没有变化，一个月后注射部位的 VEGF 受体广泛阻断。在抗 VEGF 注射后，神奇的 Rete 血管呈现出相当的介质厚度、更高的内皮增殖和凋亡，表明贝伐单抗的抗血管生成作用不会使血管壁脆弱。需要更多的研究来证实这些对血管畸形的原位抗血管生成作用的初步见解。