Schmidt Volker J, Hilgert Johannes G, Covi Jennifer M, Leibig Nico, Wietbrock Johanna O, Arkudas Andreas, Polykandriotis Elias, de Wit Cor, Horch Raymund E, Kneser Ulrich
Department of Plastic and Hand Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Department for Hand-, Plastic- and Reconstructive Surgery, BG Unfallklinik Ludwigshafen, Universität Heidelberg, Heidelberg, Germany.
Department of Plastic and Hand Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
PLoS One. 2015 Jan 30;10(1):e0117407. doi: 10.1371/journal.pone.0117407. eCollection 2015.
Exposing a vein to altered hemodynamics by creating an arteriovenous (AV) shunt evokes considerable vessel formation that may be of therapeutic potential. However, it is unclear whether the introduction of oscillatory flow and/or flow increase is decisive. To distinguish between these mechanical stimuli we grafted a femoral vein into the arterial flow pathway of the contralateral limb in rats creating an arterioarterial (AA) loop (n = 7). Alternatively, we connected the femoral artery and vein using the vein graft, whereby we created an AV-loop (n = 27). Vessel loops were embedded in a fibrin filled chamber and blood flow was measured by means of flow probes immediately after surgery (day 0) and 15 days after loop creation. On day 15, animals were sacrificed and angiogenesis was evaluated using μCT and histological analysis. Mean flow increased from 0.5 to 2.4 mL/min and was elevated throughout the cardiac cycle at day 0 in AV-loops whereas, as expected, it remained unchanged in AA-loops. Flow in AV-loops decreased with time, and was at day 15 not different from untreated femoral vessels or AA-loop grafts. Pulsatile flow oscillations were similar in AV-and AA-loops at day 0. The flow amplitude amounted to ~1.3 mL/min which was comparable to values in untreated arteries. Flow amplitude remained constant in AA-loops, whereas it decreased in AV-loops (day 15: 0.4 mL/min). A large number of newly formed vessels were present in AV-loops at day 15 arising from the grafted vein. In marked contrast, angiogenesis originating from the grafted vein was absent in AA-loops. We conclude that exposure to substantially increased flow is required to initiate angiogenesis in grafted veins, whereas selective enhancement of pulsatile flow is unable to do so. This suggests that indeed flow and most likely wall shear stress is decisive to initiate formation of vessels in this hemodynamically driven angiogenesis model.
通过创建动静脉（AV）分流使静脉暴露于改变的血流动力学中会引发大量血管形成，这可能具有治疗潜力。然而，尚不清楚振荡流的引入和/或流量增加是否起决定性作用。为了区分这些机械刺激，我们将大鼠的股静脉移植到对侧肢体的动脉血流路径中，创建了一个动脉-动脉（AA）环（n = 7）。或者，我们使用静脉移植物连接股动脉和静脉，从而创建了一个AV环（n = 27）。将血管环嵌入充满纤维蛋白的腔室中，并在手术后立即（第0天）和创建环后15天通过流量探头测量血流量。在第15天，处死动物并使用μCT和组织学分析评估血管生成。在AV环中，平均血流量从0.5 mL/min增加到2.4 mL/min，并且在第0天的整个心动周期中均升高，而正如预期的那样，AA环中的血流量保持不变。AV环中的血流量随时间减少，并且在第15天时与未处理的股血管或AA环移植物没有差异。在第0天，AV环和AA环中的脉动流振荡相似。流量幅度约为1.3 mL/min，与未处理动脉中的值相当。AA环中的流量幅度保持恒定，而AV环中的流量幅度则下降（第15天：0.4 mL/min）。在第15天，AV环中存在大量由移植静脉产生的新形成血管。与之形成鲜明对比的是，AA环中不存在源自移植静脉的血管生成。我们得出结论，移植静脉中启动血管生成需要暴露于显著增加的流量，而脉动流的选择性增强则无法做到这一点。这表明在这个血流动力学驱动的血管生成模型中，流量以及很可能的壁面剪应力确实是启动血管形成的决定性因素。
