Effects of shear stress on the intimal hyperplasia of autogenous Vein grafts

晚期移植物失效仍然是一个重要的问题，特别是在具有不良径流（低剪切应力）血管的情况下。我们已经报道过，在低流量模型中自体静脉移植物的内膜厚度明显大于正常流量组。内皮素通过释放前列环素或内皮源性舒张因子<一氧化氮（NO）>来调节基础血管平滑肌的反应性。这些因子不仅是血管扩张剂，而且是血小板聚集的有效抑制剂。本实验旨在通过使用贫径流模型来检查在贫径流条件下犬自体静脉移植物的前列环素或NO的产生是否改变。在以低剪切应力为特征的异常流动条件下，犬静脉移植物中前列环素的产生低于正常流动条件下。此外，在犬静脉移植物中NO的产生也在不良的径流条件下受损。海洋油和高水平的二十碳五烯酸（EPA）防止静脉移植物内膜增厚。然而，EPA防止内膜增厚的确切机制仍然未知。本实验旨在研究EPA补充是否会改变狗静脉移植物中NO的产生。目前的结果表明，EPA补充减少了自体静脉移植物的内膜增厚，这些结果表明，在异常流动条件下，内皮功能障碍，即前列环素或NO的产生减少，可能因此增加血小板聚集，并最终促进外周动脉闭塞性疾病的发展，从而发生晚期血栓形成。移植失败内皮功能的保留或增强可能对预防移植物晚期衰竭有重要作用。

Late graft failure is still a significant problem particularly in cases with poor runoff (low shear stress) vessels. We have already reported that the intimal thickening of the autogenous vein graft in the poor runoff model was significantly thicker than that in normal flow group. Endothelium modulates the responsiveness of the underlying vascular smooth muscles by releasing prostacyclin or endothelium-derived relaxing factor <Nitric Oxide (NO) >. These factor are not only vasodilators but also potent inhibitors of platelet aggregation. The present experiments were desingned to examine whether the production of prostacyclin or NO were altered in poor runoff conditions of canine autogenous vein grafts by using a poor runoff model. Under abnormal flow conditions characterized by low shear stress, the production of prostacyclin in the canine vein graft was lower than that in normal flow conditions. In addition, the production of NO in canine vein grafts are also impaired under poor runoff conditions.Marine oils and high levels of eicosapentanoic acid (EPA) prevents intimal thickening in vein grafts. However, the precise mechanism by which EPA prevents intimal thickening is still unknown. The present experiments was designed toexamine whether EPA supplementation would alter the NO production in reversed vein grafts of dogs. The presents results demonstrated that EPA supplementation reduces intimal thickening of the autogenous vein graft, which may be due to an improved release of NO.These results suggest that the dysfunction of the endothelium in terms of the decreased production of prostacyclin or NO under abnormal flow conditions may thus increase platelet aggregation and eventually facilitate the development of peripheral arterial occlusive disease and thus the occurrence of late graft failure. The preserved or enhanced endothelial function may be important role for preventing the late graft failure.