Chaux A, Ruan X M, Fishbein M C, Sandhu M, Matloff J M
Department of Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, Calif., USA.
J Thorac Cardiovasc Surg. 1995 Nov;110(5):1381-9; discussion 1389-90. doi: 10.1016/S0022-5223(95)70061-7.
Coronary saphenous vein grafts in human beings have a more limited long-term patency rate than internal thoracic artery grafts, primarily because of more rapid development of arteriosclerosis. The factors responsible for this increased susceptibility are not completely understood. To test the hypothesis that vein valves may influence this process, we studied 48 hypercholesterolemic rabbits with jugular vein grafts interposed into the carotid arterial circulation. In 24 animals (group A), the vein segments did not contain a vein valve. In the other 24 animals (group B), a vein valve was present. Both groups were further divided in four subgroups of six to be put to death at 2, 4, 6, and 8 weeks after the operation. All animals were fed a 2% cholesterol diet. At postmortem examination, alternate 2 mm sections were either stained with hematoxylin and eosin for histologic and morphometric studies or frozen in liquid nitrogen for immunohistochemistry and in situ hybridization studies. Proliferating cell nuclear antigen immunostaining was used to study cell proliferation. Wall thickness of vein grafts increased with time. During the first 2 weeks intimal and medial thickening was primarily due to an increase in numbers of cells. Between 2 and 6 weeks further intimal and medial thickening occurred, but without additional increase in cell numbers. After 6 weeks, foam cells and lipid deposits started to appear. By 8 weeks, changes identical to those seen in arteriosclerotic plaques in human beings were evident. These changes developed sooner and with more intensity in group B animals (p < 0.01 to 0.001), and they developed faster and with more severity in segments of vein located distal to the valve than in the segments located proximal to the valve (p < 0.001). This is the first controlled experiment demonstrating that the presence of valves in the vein segments is associated with augmented and accelerated intimal changes leading to vein atheromatosis.
在人类中，冠状动脉大隐静脉移植物的长期通畅率比胸廓内动脉移植物更有限，主要是因为动脉硬化发展更快。导致这种易感性增加的因素尚未完全了解。为了检验静脉瓣膜可能影响这一过程的假设，我们研究了48只高胆固醇血症兔子，将颈静脉移植物置于颈动脉循环中。在24只动物（A组）中，静脉段不含静脉瓣膜。在另外24只动物（B组）中，存在静脉瓣膜。两组进一步分为四个亚组，每组6只，在手术后2、4、6和8周处死。所有动物均喂食2%胆固醇饮食。在尸检时，每隔2毫米的切片要么用苏木精和伊红染色用于组织学和形态计量学研究，要么在液氮中冷冻用于免疫组织化学和原位杂交研究。使用增殖细胞核抗原免疫染色来研究细胞增殖。静脉移植物的壁厚度随时间增加。在最初的2周内，内膜和中膜增厚主要是由于细胞数量增加。在2至6周之间，内膜和中膜进一步增厚，但细胞数量没有进一步增加。6周后，泡沫细胞和脂质沉积开始出现。到8周时，与人类动脉粥样硬化斑块中所见相同的变化明显。这些变化在B组动物中出现得更早且更强烈（p<0.01至0.001），并且在瓣膜远端的静脉段比瓣膜近端的静脉段发展得更快且更严重（p<0.001）。这是第一个对照实验，证明静脉段中瓣膜的存在与内膜变化的增强和加速有关，导致静脉粥样硬化。
