A novel vein graft model: adaptation to differential flow environments

A novel vein graft model: adaptation to differential flow environments
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DOI:
10.1152/ajpheart.00760.2003
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发表时间:
2004-01-01
影响因子:
4.8
通讯作者:
Berceli, SA
Berceli, SA
中科院分区:
医学2区
文献类型:
--
作者:
Jiang, ZH;Wu, LZ;Berceli, SA

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血流环境改变引起的内膜加速增生是静脉旁路移植失败的关键。缺乏可重复的动物模型解剖静脉移植物(VG)重塑的机制,限制了解决这一临床重要问题的进展。将套囊吻合技术与其他手术操作相结合,我们开发了一种定义明确、更稳健的方法,用于研究VG动脉化中的血流动力学因素。在56只家兔的颈动脉中进行了血管成形术,包括瘘管置入、完全闭塞或部分远端分支结扎(DBL)。进行了广泛的血液动力学和生理学分析,以确定1-28天时壁的血液动力学力和组织学适应性。吻合时间平均为12分钟,双侧移植物和单侧移植物的通畅率为100%,无辅助或延迟瘘。双侧VG-DBL导致壁剪切力即刻差异(0.8 +/- 0.1 vs. 12.4 +/- 1.1 dyn/cm(2),结扎vs.对侧移植物)。暴露于低剪切应力的移植物主要通过增强的内膜增厚(231 +/- 35 vs. 36 +/- 18 mum,低剪切vs.高剪切)作出反应。高剪切应力移植物通过增强的向外重塑进行适应,28天时管腔直径增加24%(3.0 +/- 0.1与3.7 +/- 0.2 mm,低剪切与高剪切)。我们利用了套囊吻合技术,并将其与双侧VG-DBL模型相结合,以分析血流动力学对VG动脉化的影响。这种新的模型提供了一个强大的,临床相关的,统计学上强大的小动物模型的高和低剪切调节VG重塑的评价。
Accelerated intimal hyperplasia in response to altered flow environment is critical to the process of vein bypass graft failure. Lack of a reproducible animal model for dissecting the mechanisms of vein graft (VG) remodeling has limited progress toward solving this clinically significant problem. Combining a cuffed anastomotic technique with other surgical manipulations, we developed a well-defined, more robust method for studying hemodynamic factors in VG arterialization. VG with fistula placement, complete occlusion, or partial distal branch ligation (DBL) was performed in the carotid artery of 56 rabbits. Extensive hemodynamic and physiological analyses were performed to define the hemodynamic forces and histological adaptations of the wall at 1-28 days. Anastomotic time averaged 12 min, with 100% patency of bilateral grafts and unilateral grafts plus no adjunct or delayed fistula. Bilateral VG-DBL resulted in an immediate disparity in wall shear (0.8 +/- 0.1 vs. 12.4 +/- 1.1 dyn/cm(2), ligated vs. contralateral graft). Grafts exposed to low shear stress responded primarily through enhanced intimal thickening (231 +/- 35 vs. 36 +/- 18 mum, low vs. high shear). High-shear-stress grafts adapted through enhanced outward remodeling, with a 24% increase in lumen diameter at 28 days (3.0 +/- 0.1 vs. 3.7 +/- 0.2 mm, low vs. high shear). We have taken advantage of the cuffed anastomotic technique and combined it with a bilateral VG-DBL model to dissect the impact of hemodynamic forces on VG arterialization. This novel model offers a robust, clinically relevant, statistically powerful small animal model for evaluation of high- and low-shear-regulated VG remodeling.