血流剪切力对支架内新生动脉粥样硬化形成的影响
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摘要
目的:探讨血流剪切力对支架内新生粥样硬化斑块形成的影响。方法:在6只新西兰白兔右髂动脉植入金属裸支架,术后高脂喂养8周。将支架按长度均等分为近中远3段,应用多普勒超声测量各支架段血管的血流速度和血管内径,根据Poiseuille定律计算出术后即刻及术后8周时各支架段的平均血流剪切力。应用光学相干断层成像技术(optical coherence tomography,OCT)检测术后8周支架内新生内膜的生长情况及特性。结果:成功建立支架内斑块动物模型。术后即刻近中远支架段的血流剪切力分别为4.25±0.92,2.49±1.07,1.67±0.49Pa(P<0.05);术后8周近中远支架段血流剪切力分别为20.40±6.07,11.09±1.74,7.97±0.26Pa(P<0.05),均较术后即刻明显升高(P<0.001);术后8周近中远支架段的内膜异质性发生率分别为86.67%,53.33%,41.12%(P<0.05);术后8周近中远支架段OCT检测的富含脂质斑块的发生率分别为53.3%,20%,0%(P<0.05)。结论:支架内新生粥样硬化斑块的发生可能与较高的血流剪切力相关。
Objective: To study the impact of shear stress on the formation of in-stent neoatherosclerosis. Methods: The bare-metal stents were implanted in the right iliac arteries of 6 New Zealand White rabbits, which were then fed with a high-fat diet for additional 8 weeks. Each implanted stent was equally divided into 3 segments and the blood flow velocity and blood vessel diameter was measured with Doppler ultrasound. The average shear stress forces were calculated immediately after and 8 weeks after stent implantation according to Poiseuille's law. The characteristics of in-stent neointima 8 weeks after stent implantation were evaluated using optical coherence tomography. Results: An experimental animal model of in-stent neoatherosclerosis was successfully established. Shear stress forces of the proximal-, middle-and distal-stent segments were 4.25±0.92, 2.49±1.07, 1.67±0.49 Pa(P<0.05) immediately after stent implantation, which significantly increased to 20.40 ±6.07, 11.09 ±1.74, 7.97 ±0.26 Pa respectively(P <0.05) after 8 weeks(the differences between baseline and follow-up, all P <0.001).The incidence of neointima heterogeneity of proximal-, middle-, distal-stent segments 8 weeks after stent implantation were 86.67%,53.33%,41.12%(P<0.05) and the occurrences of in-stent neoatherosclerosis of the 3 segments were 53.3%, 20%, 0% respectively(P <0.05). Conclusions: These data suggests that the formation of in-stent neoatherosclerosis may be associated with higher shear stress.
Objective: To study the impact of shear stress on the formation of in-stent neoatherosclerosis. Methods: The bare-metal stents were implanted in the right iliac arteries of 6 New Zealand White rabbits, which were then fed with a high-fat diet for additional 8 weeks. Each implanted stent was equally divided into 3 segments and the blood flow velocity and blood vessel diameter was measured with Doppler ultrasound. The average shear stress forces were calculated immediately after and 8 weeks after stent implantation according to Poiseuille's law. The characteristics of in-stent neointima 8 weeks after stent implantation were evaluated using optical coherence tomography. Results: An experimental animal model of in-stent neoatherosclerosis was successfully established. Shear stress forces of the proximal-, middle-and distal-stent segments were 4.25±0.92, 2.49±1.07, 1.67±0.49 Pa(P<0.05) immediately after stent implantation, which significantly increased to 20.40 ±6.07, 11.09 ±1.74, 7.97 ±0.26 Pa respectively(P <0.05) after 8 weeks(the differences between baseline and follow-up, all P <0.001).The incidence of neointima heterogeneity of proximal-, middle-, distal-stent segments 8 weeks after stent implantation were 86.67%,53.33%,41.12%(P<0.05) and the occurrences of in-stent neoatherosclerosis of the 3 segments were 53.3%, 20%, 0% respectively(P <0.05). Conclusions: These data suggests that the formation of in-stent neoatherosclerosis may be associated with higher shear stress.
引文
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[18]Guo FX,Hu YW,Zheng L,et al.Shear Stress in Autophagy and Its Possible Mechanisms in the Process of Atherosclerosis[J].DNA Cell Biol,2017,36(5):335-346
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[23]Uemiya N,Lee CJ,Ishihara S,et al.Analysis of restenosis after carotid artery stenting:preliminary results using computational fluid dynamics based on three-dimensional angiography[J].J Clin Neurosci,2013,20(11):1582-1587
[24]Carter AJ,Wei W,Gibson L,et al.Segmental vessel wall shear stress and neointimal formation after sirolimus-eluting stent implantation:physiological insights in a porcine coronary model[J].Cardiovasc Revasc Med,2005,6(2):58-64
[2]Ong DS,Jang IK.Causes,assessment,and treatment of stent thrombosis--intravascular imaging insights[J].Nat Rev Cardiol,2015,12(6):325-336
[3]Souteyrand G,Amabile N,Mangin L,et al.Mechanisms of stent thrombosis analysed by optical coherence tomography:insights from the national PESTO French registry[J].Eur Heart J,2016,37(15):1208-1216
[4]Otsuka F,Byrne RA,Yahagi K,et al.Neoatherosclerosis:overview of histopathologic findings and implications for intravascular imaging assessment[J].Eur Heart J,2015,36(32):2147-2159
[5]Kawakami R,Hao H,Tsuchida YA,et al.Neoatherosclerosis after paclitaxel-eluting stent implantation:Ex vivo intravascular image and histopathology[J].Pathol Int,2017,67(1):53-55
[6]Nakamura D,Attizzani GF,Toma C,et al.Failure Mechanisms and Neoatherosclerosis Patterns in Very Late Drug-Eluting and Bare-Metal Stent Thrombosis[J].Circ Cardiovasc Interv,2016,9(9).[Epub ahead of print]
[7]Cui Y,Liu Y,Zhao F,et al.Neoatherosclerosis after Drug-Eluting Stent Implantation:Roles and Mechanisms[J].Oxid Med Cell Longev,2016,2016:5924234
[8]Ng J,Bourantas CV,Torii R,et al.Local Hemodynamic Forces After Stenting:Implications on Restenosis and Thrombosis[J].Arterioscler Thromb Vasc Biol,2017,37(12):2231-2242
[9]Papafaklis MI,Takahashi S,Antoniadis AP,et al.Effect of the local hemodynamic environment on the de novo development and progression of eccentric coronary atherosclerosis in humans:insights from PREDICTION[J].Atherosclerosis,2015,240(1):205-211
[10]Green JP,Souilhol C,Xanthis I,et al.Atheroprone flow activates inflammation via endothelial ATP-dependent P2X7-p38 signalling[J].Cardiovasc Res,20[Epub ahead of print]
[11]Feng S,Bowden N,Fragiadaki M,et al.Mechanical Activation of Hypoxia-Inducible Factor 1alpha Drives Endothelial Dysfunction at Atheroprone Sites[J].Arterioscler Thromb Vasc Biol,2017,37(11):2087-2101
[12]杜丽珍,康卫华.超声评价兔腹主动脉粥样硬化与血流剪切力关系的实验研究[J].山西医药杂志,2008,4(37):297-300Du Li-zhen,Cao Wei-hua.Experimental study of relationship between atherosclerosis and fluid shear stress in rabbits with ultrasound[J].Shanxi Medical Journal,2008,4(37):291-300
[13]Timmins LH,Molony DS,Eshtehardi P,et al.Oscillatory wall shear stress is a dominant flow characteristic affecting lesion progression patterns and plaque vulnerability in patients with coronary artery disease[J].J R Soc Interface,2017,14(127)[Epub ahead of print]
[14]Komatsu R,Ueda M,Naruko T,et al.Neointimal tissue response at sites of coronary stenting in humans:macroscopic,histological,and immunohistochemical analyses[J].Circulation,1998,98(3):224-233
[15]Farb A,Kolodgie FD,Hwang JY,et al.Extracellular matrix changes in stented human coronary arteries[J].Circulation,2004,110(8):940-947
[16]Kimura T,Abe K,Shizuta S,et al.Long-term clinical and angiographic follow-up after coronary stent placement in native coronary arteries[J].Circulation,2002,105(25):2986-2991
[17]Nakazawa G,Otsuka F,Nakano M,et al.The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents[J].J Am Coll Cardiol,2011,57(11):1314-1322.
[18]Guo FX,Hu YW,Zheng L,et al.Shear Stress in Autophagy and Its Possible Mechanisms in the Process of Atherosclerosis[J].DNA Cell Biol,2017,36(5):335-346
[19]Zhang B,Gu J,Qian M,et al.Correlation between quantitative analysis of wall shear stress and intima-media thickness in atherosclerosis development in carotid arteries[J].Biomed Eng Online,2017,16(1):137
[20]Kim C,Kim BK,Lee SY,et al.Incidence,clinical presentation,and predictors of early neoatherosclerosis after drug-eluting stent implantation[J].Am Heart J,2015,170(3):591-597
[21]Jenei C,Balogh E,Szabo GT,et al.Wall shear stress in the development of in-stent restenosis revisited.A critical review of clinical data on shear stress after intracoronary stent implantation[J].Cardiol J,2016,23(4):365-373
[22]Shishido K,Antoniadis AP,Takahashi S,et al.Effects of Low Endothelial Shear Stress After Stent Implantation on Subsequent Neointimal Hyperplasia and Clinical Outcomes in Humans[J].J Am Heart Assoc,2016,5(9[Epub ahead of print]
[23]Uemiya N,Lee CJ,Ishihara S,et al.Analysis of restenosis after carotid artery stenting:preliminary results using computational fluid dynamics based on three-dimensional angiography[J].J Clin Neurosci,2013,20(11):1582-1587
[24]Carter AJ,Wei W,Gibson L,et al.Segmental vessel wall shear stress and neointimal formation after sirolimus-eluting stent implantation:physiological insights in a porcine coronary model[J].Cardiovasc Revasc Med,2005,6(2):58-64