Hanratty Colm G, Murrell Melanie, Khachigian Levon M, Tsao Philip S, Ward Michael R
Vascular Biology Laboratory, Cardiology Department, Royal North Shore Hospital, Sydney, Australia.
Atherosclerosis. 2004 Dec;177(2):269-74. doi: 10.1016/j.atherosclerosis.2004.07.016.
Low flow (LF) promotes late lumen loss after angioplasty by exacerbating inward remodelling through redox-sensitive mechanisms. Stents eliminate inward remodelling and the effect of LF on in-stent restenosis is uncertain. We performed over-sized (1.3-1.5:1) stenting (S) and balloon injury (in the same vessel, B) to the carotid arteries of cholesterol-fed rabbits and compared 28-day late lumen loss with that in an uninjured segment in the same vessel (U). Vessels (n = 5 animals per group) were subjected to high (H), normal (N) and low (L) flow in animals fed either vehicle (V) or the antioxidant pyrrolidine dithiocarbamate, PDTC (P). LF significantly increased in-stent neointima formation relative to normal and high flow (SLV 0.72 +/- 0.07 mm(2) versus SNV 0.43 +/- 0.08 mm(2) versus SHV 0.28 +/- 0.04 mm(2), P < 0.05). However, LF resulted in greater lumen loss in segments from the same vessel subject to balloon injury (lumen SLV 5.18 +/- 0.40 mm(2) and SNV 5.32 +/- 0.40 mm(2) versus BLV 1.28 +/- 0.33 mm(2) and BNV 2.19 +/- 0.28 mm(2)), by greater enhancement of inward remodelling. In addition, inward remodelling and lumen loss due to LF were greater in balloon-injured segments than in adjacent uninjured segments where shear homeostatic remodelling occurs (lumen BLV 1.28 +/- 0.33 mm(2) versus ULV 1.52 +/- 0.22 mm(2)). Lastly, while PDTC effectively reduced intima formation and inward remodelling due to LF in balloon-injured vessels there was no effect on flow-dependent neointima formation in stented vessels. We conclude that LF accentuates in-stent neointima formation, but that flow-dependent lumen loss after stenting is less than that after balloon injury. When LF is present lumen loss can be minimised by antioxidants or stenting.
低流量（LF）通过氧化还原敏感机制加剧内向重塑，从而促进血管成形术后的晚期管腔丢失。支架可消除内向重塑，而LF对支架内再狭窄的影响尚不确定。我们对喂食胆固醇的家兔颈动脉进行了超大尺寸（1.3 - 1.5:1）的支架置入（S）和球囊损伤（在同一血管内，B），并将28天的晚期管腔丢失与同一血管未损伤节段（U）的情况进行比较。在喂食载体（V）或抗氧化剂吡咯烷二硫代氨基甲酸盐（PDTC，P）的动物中，血管（每组n = 5只动物）分别接受高（H）、正常（N）和低（L）流量。相对于正常流量和高流量，LF显著增加了支架内新生内膜形成（SLV内膜面积0.72 ± 0.07 mm²，SNV内膜面积0.43 ± 0.08 mm²，SHV内膜面积0.28 ± 0.04 mm²，P < 0.05）。然而，LF导致同一血管接受球囊损伤节段的管腔丢失更大（SLV管腔面积5.18 ± 0.40 mm²，SNV管腔面积5.32 ± 0.40 mm²，而BLV管腔面积1.28 ± 0.33 mm²，BNV管腔面积2.19 ± 0.28 mm²），原因是内向重塑增强。此外，球囊损伤节段中由于LF导致的内向重塑和管腔丢失比发生剪切稳态重塑的相邻未损伤节段更大（BLV管腔面积1.28 ± 0.33 mm²，而ULV管腔面积1.52 ± 0.22 mm²）。最后，虽然PDTC有效地减少了球囊损伤血管中由于LF导致的内膜形成和内向重塑，但对支架置入血管中流量依赖性内膜形成没有影响。我们得出结论，LF会加剧支架内新生内膜形成，但支架置入后流量依赖性管腔丢失小于球囊损伤后。当存在LF时，抗氧化剂或支架置入可使管腔丢失最小化。
