HYPERCHOLESTEROLEMIA AND EXPERIMENTAL VEIN GRAFTS - ACCELERATED DEVELOPMENT OF INTIMAL HYPERPLASIA AND AN INCREASE IN ABNORMAL VASOMOTOR FUNCTION
HYPERCHOLESTEROLEMIA AND EXPERIMENTAL VEIN GRAFTS - ACCELERATED DEVELOPMENT OF INTIMAL HYPERPLASIA AND AN INCREASE IN ABNORMAL VASOMOTOR FUNCTION
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DOI：
10.1006/jsre.1993.1071
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发表时间：
1993-05-01
影响因子：
2.2
通讯作者：
HAGEN, PO
中科院分区：
文献类型：
--
作者：
KLYACHKIN, ML;DAVIES, MG;HAGEN, PO
高胆固醇血症是动脉粥样硬化发展的重要危险因素。晚期静脉移植物失败归因于内膜增生和动脉粥样硬化的结合。本研究探讨了高胆固醇血症对实验性静脉移植物早期形态和血管功能的影响。40只新西兰白色家兔在手术前4周接受1%胆固醇饲料（n= 24; HC）或标准饲料（n= 16; CON），此后直至收获。所有动物均接受反向静脉颈总动脉旁路术。分别于术后2周和4周取移植静脉和对侧静脉进行组织学和形态计量学分析（每组n= 8），或用5-羟色胺（5-HT）、去甲肾上腺素（NE）、缓激肽（BK）和内皮素-1（ET）进行体外等长张力研究，并观察NE预收缩后，乙酰胆碱（ACh）和硝普钠（SNP）对血管的舒张反应。在胆固醇饮食的4、6和8周后测量血清胆固醇水平。高胆固醇血症动物的血清胆固醇浓度始终比对照组高20至30倍。与相应的对照组相比，HC组移植物的内膜面积在2周时增加了两倍，在4周时增加了三倍。与CON静脉移植物相比，HC静脉移植物的内膜主要由载脂平滑肌细胞组成，在内膜和中膜之间有散在的巨噬细胞和偶尔的脂质斑块。所有移植物的内侧区域相似。HC移植物在2周和4周时对5-HT变得越来越敏感。HC移植物对NE和BK的超敏感性在4周时出现。对ET的敏感性没有变化。虽然没有移植放松ACh，HC移植收缩在低剂量。所有移植物均以剂量依赖性方式对SNP作出反应。与CON静脉相反，HC静脉表现出对NE的敏感性增加和对5-HT的收缩反应（仅在4周时）。HC静脉对ACh的反应不呈剂量依赖性。未观察到HC静脉的形态学变化。HC引起静脉移植物的结构变化和相关的血管异常。密切相关的功能变化也发生在对侧静脉。HC似乎诱导平滑肌细胞的内在变化，这与更大的增殖和异常血管扩张能力有关。在临床上，围手术期应用强有力的抗HC方案可能有利于长期保持通畅。
Hypercholesterolemia is an important risk factor for the development of atherosclerosis. Late vein graft failure has been attributed to a combination of both intimal hyperplasia and atherosclerosis. This study examines the effect of hypercholesterolemia on the early morphology and vasomotor function of experimental vein grafts. Forty New Zealand White rabbits received either a 1% cholesterol diet (n= 24; HC) or a standard diet (n= 16; CON) for 4 weeks before operation and thereafter until harvest. All animals underwent a reversed vein common carotid artery bypass. The vein grafts and contralateral veins were harvested at 2 and 4 weeks after operation in both groups for either histological and morphometric analysis (n= 8 for each group) or forin vitroisometric tension studies using serotonin (5-HT), norepinephrine (NE), bradykinin (BK), and endothelin-1 (ET) and following NE precontraction, relaxation in response to acetylcholine (ACh) and sodium nitroprusside (SNP). Serum cholesterol levels were measured after 4, 6, and 8 weeks of the cholesterol diet. Serum cholesterol concentrations were 20 to 30 times higher than controls in the hypercholesterolemic animals at all times. The intimal area of the grafts in the HC group increased by twofold at 2 weeks and threefold at 4 weeks compared to corresponding controls. In contrast to the CON vein grafts, the intima of the vein grafts from HC consisted mainly of lipid-laden smooth muscle cells with scattered interspersed macrophages and occasional lipid plaques between the intima and the media. Medial areas were similar in all grafts. HC grafts became progressively more sensitive to 5-HT at 2 and 4 weeks. A supersensitivity to NE and BK developed at 4 weeks in HC grafts. There was no change in sensitivity to ET. While no graft relaxed to ACh, HC grafts contracted at low doses. All grafts responded to SNP in a dose-dependent manner. In contrast to CON veins, HC veins demonstrated an increase in sensitivity to NE and a contractile response to 5-HT (at 4 weeks only). HC veins did not relax in a dose-dependent manner in response to ACh. No changes in the morphology of HC veins were noted. HC produces changes in the structure and associated vasomotor abnormalities of vein grafts. Closely related functional changes also occur in contralateral veins. HC appears to induce intrinsic changes in smooth muscle cells which are linked to a greater proliferative and abnormal vasomotor capability. Clinically, applications of vigorous anti-HC regimens perioperatively may be beneficial in maintaining patency over the longer term.