Reduction of experimental vein graft intimal hyperplasia by ketanserin.
Reduction of experimental vein graft intimal hyperplasia by ketanserin.
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酮色林减少实验性静脉移植物内膜增生。
DOI：
10.1006/jsre.1993.1082
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Hagen,PO
中科院分区：
文献类型：
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作者：
Massey,MF;Davies,MG;Svendsen,E;Klyachkin,ML;Schwartz,LB;Barber,L;McCann,RL;Hagen,PO
血管内膜增生被认为是平滑肌细胞增殖的结果。兔实验性静脉移植物(VG)在5-HT2受体的介导下，对5-羟色胺(5-HT)产生收缩反应和内膜增生。已知5-羟色胺能刺激体外培养的血管平滑肌细胞增殖，因此可能与内膜增生的发生有关。本研究观察了5-HT2拮抗剂酮丝氨酸(KT)对移植静脉移植后14天和28天的形态和功能的影响。43只新西兰大白兔接受了颈总动脉间置搭桥术。22例患者术前5天给予KT(0.86 mg/kg/d，po)，术后至收获。其余21只动物作为对照。分别于第14天(VG14)和第28天(VG28)取VG作组织学或血管反应性检查。采用加压固定法获取23只VG，对移植物的中段进行视频形态测量。对其余20个室上性心动过速的环进行5-羟色胺和去甲肾上腺素(NE)的标准等长张力研究。对两组的对侧颈外静脉(CV)进行研究，以评估KT的功能毒性。KT指出，它没有毒性影响。与对照组相比，KT治疗14天或28天时并不影响CV的功能活动。与对照组相比，KT组血管内膜厚度显著减少(49±11vs113±24μm；P=0.04)，管腔面积显著增加(16.89±2.13vs8.41±1.50mm2；P<；0.02)。在第14天和第28天，KT组与对照组相比，对NE或5-HT的敏感性没有变化。与对照组相比，经KT处理的移植物对去甲肾上腺素和5-羟色胺的最大张力在VG14增加(NE，0.42±0.2vs0.21±0.05g；5-HT0.68±0.37vs0.31±0.11g；P>；0.05)，在VG28显著增加(NE，1.42±0.38vs0，47±0.06g；5-HT1.44±0.46vs0.3±0.18g；P<；0.05)。综上所述，本研究表明，KT减少了VG内的内膜增生厚度，增加了VG内平滑肌细胞的反应性，使管腔面积增加了一倍。因此，KT的短期治疗可能有助于控制血管重建患者的内膜增生。
Intimal hyperplasia is considered to be the result of smooth muscle cell proliferation. Experimental vein grafts (VG) in the rabbit develop intimal hyperplasia and a contractile response to serotonin (5-HT), mediated by a 5-HT2receptor. 5-HT is known to stimulate smooth muscle cell proliferationin vitroand therefore may be linked to the development of intimal hyperplasia. This study examines the effect of a 5-HT2antagonist, ketanserin (KT) on vein graft morphology and function at 14 and 28 days after grafting. Forty-three New Zealand White rabbits underwent common carotid interposition bypass grafting. Twenty-two were treated with KT (0.86 mg/kg/day po) 5 days prior to surgery and thereafter until harvest. The remaining 21 animals acted as controls. VG were harvested at 14 (VG14) and 28 (VG28) days for histology or vasoreactivity. Twenty-three VG were harvested by pressure fixation and the midportions of the grafts were examined by videomorphometry. Standard isometric tension studies in response to serotonin and norepinephrine (NE) were performed on the rings from the remaining 20 VG. Contralateral external jugular veins (CV) from both groups were studied to assess the functional toxicity of KT. There were no toxic effects to KT noted. KT therapy did not affect the functional activity of the CV at 14 or 28 days when compared to controls. When compared to controls, KT significantly reduced the intimal thickness (49 ± 11 vs 113 ± 24 μm;P= 0.04) and there was an increase in luminal area (16.89 ± 2.13 vs 8.41 ± 1.50 mm2;P< 0.02) in VG28 only. There were no changes in sensitivity to NE or 5-HT in the KT group compared to the controls at either 14 or 28 days. In KT-treated grafts compared to control grafts maximal tensions in response to NE and 5-HT were increased in VG14 (NE, 0.42 ± 0.2 vs 0.21 ± 0.05 g; 5-HT, 0.68 ± 0.37 vs 0.31 ± 0.11 g;P> 0.05) and were significantly greater in VG28 (NE, 1,42 ± 0.38 vs 0,47 ± 0.06 g; 5-HT, 1.44 ± 0.46 vs 0.3 ± 0.18 g;P< 0.05). In conclusion, this study shows that KT reduces the thickness of intimal hyperplasia with an increase in the responsiveness of smooth muscle cells in VG and a twofold increase in luminal area. Therefore, short-term therapy with KT may be beneficial in controlling intimal hyperplasia in the revascularized patient.