动脉粥样硬化斑块失稳破裂的粘弹性动力学研究和临床应用
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摘要
动脉粥样硬化斑块的破裂是导致急性心血管事件的触发因素,基于临床观测的研究对动脉粥样硬化斑块的破裂做出一部分解释,总结了不稳定斑块的特征.但是斑块的破裂机制至今还没有一个完整的数学模型可以解释,苏海军等从弹性力学稳定性理论出发,利用有矩理论,建立了动脉粥样硬化斑块纤维帽的动力学模型,提出纤维帽的参数共振导致斑块破裂的新机制,得到与临床结果相符合的结论.本文基于动力学模型,视斑块脂核为粘弹性固体,研究动脉粥样硬化斑块脂核在斑块失稳破裂中的作用,证明在纤维帽的参数共振中,存在一个脉动基频稳定区域和三个不稳定区域,当斑块的自身属性和周边环境满足稳定区域的条件时,斑块稳定,当斑块的本质属性和周边环境满足不稳定区域的条件,斑块将因参数共振破裂.周边环境包括脉压和脉动基频.全文总计四章.
第一章为研究背景.介绍动脉粥样硬化的病理学基础,不稳定斑块观点的由来及常见特征,最新进展不稳定病人观点的内涵,同时回顾了目前斑块破裂的生物力学研究进展及临床上的最新结果,简要介绍了带粘性项的参数共振及本文的主要方法.
第二章视动脉粥样硬化斑块脂核为Klevin-Voigt型粘弹性固体,分析动脉粥样硬化斑块内容物对纤维帽运动的影响,建立耦合动力学模型。推导出斑块存在一个脉动频率稳定区域和三个脉动频率不稳定区域,每一个不稳定区域中都存在引发纤维帽参数共振的脉动频率,讨论了外在平均血压、脉压和斑块内在粘性指标和弹性指标对斑块稳定性的影响.
第三章从两方面评价斑块的稳定性,包含患者稳定状态的动态评估和斑块内在稳定性的评估.在患者稳定状态的动态评估中,分析血压的均值和脉压对斑块稳定性的影响.在斑块内在稳定性评估中,分析斑块的内在属性和几何形状对斑块稳定性的影响.
第四章为总结.阐述耦合动力学模型中斑块破裂的机制和斑块的各参数对斑块稳定性的影响.
Rupture of atherosclerotic plaque is the main trigger of acute cardiovascular events, though,the study based on the clinical experiments explained some facts of atherosclerotic plaque rupture and summarized some characteristics of instable plaque.The mechanism of plaque rupture is still unknown. Haijunsu et al,constructed a mathematical model to describe the motion of the fibrous cap using the theory of elastic mechanics. The results obtained from the model were consistent with the clinical experiments. The model in this article is based on the previous model and we studies the effect of the content in the atherosclerotic plaque considering the content as the Kelvin-Voigt solid. We obtain a stable pulse frequency region and three instable pulse frequency regions,in which the plaque may rupture in the motion of parametric resonance when the blood frequency falls in the dangerous frequency regions.The plaque is stable when the conditions in the stable region are fulfilled. The conditions include the blood pressure and the pulse frequency.This article is composed of four chapters.
In the first chapter,we first introduced the pathology foundation of atheroscle-rosis, the viewpoint of the vulnerable plaque as well as the common characteristic, briefly reviewed the progress in biomechanical studies of plaque rupture,the new re-sults obtained from the clinic experiments, then introduced the theory of parametric resonance and the main methods in this article.
In the second chapter, assuming the lipid core of atherosclerotic plaque as the Kelvin-Voigt solid,we construct the coupled dynamics model and discuss the motion of fibrous cap affected by the content, we find that there are a pulse frequency stable region and three instable regions, in which the frequency region making the fibrous cap paramctric resonance is different. We discuss the plaque stability affected by the average blood pressure,the pulse pressure,the viscosity indexγand the elasticity indexβ.
In the third chapter,we assess the stability of the plaque from two different sides,which concludes the dynamic assessment of patients in stable state and the Stability assessment of plaque content.We discuss the effect of the amplitude and the average of blood pressure.we also discuss the plaque stability impacted by the intrinsic properties and plaque geometry.
In the fourth chapter,we elaborate the mechanisms of plaque rupture in the coupled dynamic model and discuss the plaque stability affected by pathes of several parameters.
第一章为研究背景.介绍动脉粥样硬化的病理学基础,不稳定斑块观点的由来及常见特征,最新进展不稳定病人观点的内涵,同时回顾了目前斑块破裂的生物力学研究进展及临床上的最新结果,简要介绍了带粘性项的参数共振及本文的主要方法.
第二章视动脉粥样硬化斑块脂核为Klevin-Voigt型粘弹性固体,分析动脉粥样硬化斑块内容物对纤维帽运动的影响,建立耦合动力学模型。推导出斑块存在一个脉动频率稳定区域和三个脉动频率不稳定区域,每一个不稳定区域中都存在引发纤维帽参数共振的脉动频率,讨论了外在平均血压、脉压和斑块内在粘性指标和弹性指标对斑块稳定性的影响.
第三章从两方面评价斑块的稳定性,包含患者稳定状态的动态评估和斑块内在稳定性的评估.在患者稳定状态的动态评估中,分析血压的均值和脉压对斑块稳定性的影响.在斑块内在稳定性评估中,分析斑块的内在属性和几何形状对斑块稳定性的影响.
第四章为总结.阐述耦合动力学模型中斑块破裂的机制和斑块的各参数对斑块稳定性的影响.
Rupture of atherosclerotic plaque is the main trigger of acute cardiovascular events, though,the study based on the clinical experiments explained some facts of atherosclerotic plaque rupture and summarized some characteristics of instable plaque.The mechanism of plaque rupture is still unknown. Haijunsu et al,constructed a mathematical model to describe the motion of the fibrous cap using the theory of elastic mechanics. The results obtained from the model were consistent with the clinical experiments. The model in this article is based on the previous model and we studies the effect of the content in the atherosclerotic plaque considering the content as the Kelvin-Voigt solid. We obtain a stable pulse frequency region and three instable pulse frequency regions,in which the plaque may rupture in the motion of parametric resonance when the blood frequency falls in the dangerous frequency regions.The plaque is stable when the conditions in the stable region are fulfilled. The conditions include the blood pressure and the pulse frequency.This article is composed of four chapters.
In the first chapter,we first introduced the pathology foundation of atheroscle-rosis, the viewpoint of the vulnerable plaque as well as the common characteristic, briefly reviewed the progress in biomechanical studies of plaque rupture,the new re-sults obtained from the clinic experiments, then introduced the theory of parametric resonance and the main methods in this article.
In the second chapter, assuming the lipid core of atherosclerotic plaque as the Kelvin-Voigt solid,we construct the coupled dynamics model and discuss the motion of fibrous cap affected by the content, we find that there are a pulse frequency stable region and three instable regions, in which the frequency region making the fibrous cap paramctric resonance is different. We discuss the plaque stability affected by the average blood pressure,the pulse pressure,the viscosity indexγand the elasticity indexβ.
In the third chapter,we assess the stability of the plaque from two different sides,which concludes the dynamic assessment of patients in stable state and the Stability assessment of plaque content.We discuss the effect of the amplitude and the average of blood pressure.we also discuss the plaque stability impacted by the intrinsic properties and plaque geometry.
In the fourth chapter,we elaborate the mechanisms of plaque rupture in the coupled dynamic model and discuss the plaque stability affected by pathes of several parameters.
引文
[1]Benson,RL.The present status of coronary arterial disease[J].Arch. Pathol, 1926,2:876-916.
[2]P.Constantinides.Plaque fissures in human coronary thrombosis[J] Journal of Atherosclerosis Research,1966,Voluume 6,Issue 1,2:1-17
[3]Kullo IJ,Edwards WD,Schwartz RS.Vulnerable plaque:pathobiology and clin-ical implications[J].Ann Intern MED,1998,129(12):1050-1060
[4]Dewood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction[J]. N Engl J Med, 1980,303(16):897-902
[5]Dewood MA, Notske RN, Hensley GR, et al. Intraaortic balloon counter-pulsation with and without reperfusion for myocardial infarction shock[J]. Circulation,1980,61(6):1105-1112
[6]Brown BG, Gallery CA, Badger RS, et al. Incomplete lysis of thrombus in the moderate underlying atherosclerotic lesion during intracoronary infusion of streptokinase for acute myocardial infarction:quantitative angiographic observation[J]. Circulation,1986,73(4):653-661
[7]Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease[J]? Circulation,1988,78(5 Pt 1):1157-1166
[8]Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progres-sion of coronary artery disease and the development of myocardial infarc-tion[J]. J Am Coll Cardiol,1988,12(1):56-62
[9]Ambrose JA,Winters SL,Stem A,et al.Angiographic morphology and patho-genesis of unstable angina pectoris[J].J Am Coll Cardiol,1985,5(3):609-616
[10]Ambrose JA,Winters SL,Arora RR,et al.Coronary angiographic morphology in myocardial infarction:a link between the pathogenesis of unstable angina and myocardial infarction [J]. J Am Coll Cardiol,1985,6(6):1233-1238
[11]Ward MR,Pasterkamp G.Yeung AC,et al.Arterial remodeling.Mechanisms and clinical implications[J].Circulation,2000,102(10):1186-1191
[12]Pasterkamp G,de Kleijn DP,Borst C.Arterial remodeling in atherosclero-sis,restenosis and after alteration of blood flow:potential mechanisms and clinical implications[J].Cardiovasc Res,2000,45(4):843-852
[13]陈文强,张运,张梅,季晓平,丁士芳,陈玉国,李贵双.冠状动脉不稳定斑块血管内超声特征的临床研究[J].中国超声医学杂志,2004,20(4)：289-291
[14]Shah Pk.Mechanism of plaque vulnerability and rupture[J].J Am Coll Cardiol, 2003,41 Suppl 1:15-22.
[15]Falk E,Shah PK,Fuster V.Coronary plaque disruption[J].Circulation, 1995,92:657-71.
[16]Nobuyoshi M,Tanaka M,Nosaka H,et al.Progression of coronary atheroscle-rosis:is coronary spasm related to progression[J]? J Am Coll Cardiol, 1991,18:904-10.
[17]Giroud D,Li JM,Urban P,Meier B,Rutishauer W.Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography[J].Am J Cardiol,1992,69:729-32
[18]Loree HM,Kamm RD,Stringfellow RG,Lee RT.Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vesscls[J].Circ Res, 1992,71:850-8
[19]Koji Imoto,Takafumi Hiro,et al.Longitudinal Structural Determinants of Atherosclerotic Plaque Vulnerability:A Computational Analysis of Stress Dis-tribution Using Vessel Models and Three-Dimensional Intravascular Ultra-sound Imaging[J].J Am Coll Cardiol,2005,46;1507-1515
[20]Morteza Naghavi,Peter Libby,et al.From Vulnerable Plque to Vulnerable Patient:A Call for New Definitions and Risk Assessment Strategies:Part I [J].Circulation,2003,108:1664-1672
[21]Burke AP, Farb A, Malcom GT, et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly[J].N Engl J Med,1997,336(18):1276-1282
[22]Lee RT, Libby P.The unstable atheroma[J]. Arterioscler Thromb Vasc Biol,1997,17(10):1859-1867
[23]Ross R. Atherosclerosis an inflammatory disease[J]. N Engl J Med,1999,340(2):115-126
[24]Ku DN. Blood flow in arteries[J]. Annual Review of Fluid Mechanics,1997, 29:399-434
[25]Wootton DM, Ku DN. Fluid mechanics of vascular systems, diseases, and thrombosis[J]. Annu Rev Biomed Eng,1999,1:299-329
[26]Berger SA, Jou LD. Flows in stenotic vessels[J]. Annual Review of Fluid Mechanics,2000,32:347-382
[27]Taber LA. Biomechanics of cardiovascular development [J].Annu Rev Biomed Eng,2001,3:1-25
[28]C. P. Cannon. Management of acute coronary syndromes[J]. New Jersey: Humana Press Inc,1999
[29]Gertz SD, Roberts WC. Hemodynamic shear force in rupture of coronary arterial atherosclerotic plaques[J]. Am J Cardiol,1990,66(19):1368-1372
[30]Arroyo LH, Lee RT. Mechanisms of plaque rupture:mechanical and biologic interactions[J].Cardiovascular Research,1999,41(2):369-375
[31]Bank AJ, Versluis A, Dodge SM, et al. Atherosclerotic plaque rupture:a fatigue process[J]? Med Hypotheses,2000,55(6):480-484
[32]Jiang Y, Kohara K, Hiwada K. Association between risk factors for atheroscle-rosis and mechanical forces in carotid artery [J]. Stroke,2000,31(10):2319-2324
[33]Lee RT. Atherosclerotic lesion mechanics versus biology[J]. Z Kardiol,2000, 89 Supp12:80-84
[34]Dalin Tang,Chun Yang.Jie Zhang,Pamelak,et al.Local Maximal stress Hy-pothesis and Computational Plaque Vulnerability Index for Atherosclerotic Plaque Assessment [J].Annals of Biomedical Engineering,2005,33(12):1789-1801
[35]苏海军,张梅,张运.动脉粥样硬化斑块失稳破裂的力学模型[J].中国科学G辑,2004,34(2)：192-202
[36]A.H.奈弗,D.T.穆克.非线性振动[M].北京：高等教育出版社,1990,333-335
[37]Seemantini K. Nadkarni.Brett E.Bouma.Johannes de Boer.Guillermo J.Tearney.Evaluation of collagen in atherosclerotic plaques:the use of two co-herent laser-based imaging methods[J].Lasers Med Sci,2009,24:439-445
[2]P.Constantinides.Plaque fissures in human coronary thrombosis[J] Journal of Atherosclerosis Research,1966,Voluume 6,Issue 1,2:1-17
[3]Kullo IJ,Edwards WD,Schwartz RS.Vulnerable plaque:pathobiology and clin-ical implications[J].Ann Intern MED,1998,129(12):1050-1060
[4]Dewood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction[J]. N Engl J Med, 1980,303(16):897-902
[5]Dewood MA, Notske RN, Hensley GR, et al. Intraaortic balloon counter-pulsation with and without reperfusion for myocardial infarction shock[J]. Circulation,1980,61(6):1105-1112
[6]Brown BG, Gallery CA, Badger RS, et al. Incomplete lysis of thrombus in the moderate underlying atherosclerotic lesion during intracoronary infusion of streptokinase for acute myocardial infarction:quantitative angiographic observation[J]. Circulation,1986,73(4):653-661
[7]Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease[J]? Circulation,1988,78(5 Pt 1):1157-1166
[8]Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progres-sion of coronary artery disease and the development of myocardial infarc-tion[J]. J Am Coll Cardiol,1988,12(1):56-62
[9]Ambrose JA,Winters SL,Stem A,et al.Angiographic morphology and patho-genesis of unstable angina pectoris[J].J Am Coll Cardiol,1985,5(3):609-616
[10]Ambrose JA,Winters SL,Arora RR,et al.Coronary angiographic morphology in myocardial infarction:a link between the pathogenesis of unstable angina and myocardial infarction [J]. J Am Coll Cardiol,1985,6(6):1233-1238
[11]Ward MR,Pasterkamp G.Yeung AC,et al.Arterial remodeling.Mechanisms and clinical implications[J].Circulation,2000,102(10):1186-1191
[12]Pasterkamp G,de Kleijn DP,Borst C.Arterial remodeling in atherosclero-sis,restenosis and after alteration of blood flow:potential mechanisms and clinical implications[J].Cardiovasc Res,2000,45(4):843-852
[13]陈文强,张运,张梅,季晓平,丁士芳,陈玉国,李贵双.冠状动脉不稳定斑块血管内超声特征的临床研究[J].中国超声医学杂志,2004,20(4)：289-291
[14]Shah Pk.Mechanism of plaque vulnerability and rupture[J].J Am Coll Cardiol, 2003,41 Suppl 1:15-22.
[15]Falk E,Shah PK,Fuster V.Coronary plaque disruption[J].Circulation, 1995,92:657-71.
[16]Nobuyoshi M,Tanaka M,Nosaka H,et al.Progression of coronary atheroscle-rosis:is coronary spasm related to progression[J]? J Am Coll Cardiol, 1991,18:904-10.
[17]Giroud D,Li JM,Urban P,Meier B,Rutishauer W.Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography[J].Am J Cardiol,1992,69:729-32
[18]Loree HM,Kamm RD,Stringfellow RG,Lee RT.Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vesscls[J].Circ Res, 1992,71:850-8
[19]Koji Imoto,Takafumi Hiro,et al.Longitudinal Structural Determinants of Atherosclerotic Plaque Vulnerability:A Computational Analysis of Stress Dis-tribution Using Vessel Models and Three-Dimensional Intravascular Ultra-sound Imaging[J].J Am Coll Cardiol,2005,46;1507-1515
[20]Morteza Naghavi,Peter Libby,et al.From Vulnerable Plque to Vulnerable Patient:A Call for New Definitions and Risk Assessment Strategies:Part I [J].Circulation,2003,108:1664-1672
[21]Burke AP, Farb A, Malcom GT, et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly[J].N Engl J Med,1997,336(18):1276-1282
[22]Lee RT, Libby P.The unstable atheroma[J]. Arterioscler Thromb Vasc Biol,1997,17(10):1859-1867
[23]Ross R. Atherosclerosis an inflammatory disease[J]. N Engl J Med,1999,340(2):115-126
[24]Ku DN. Blood flow in arteries[J]. Annual Review of Fluid Mechanics,1997, 29:399-434
[25]Wootton DM, Ku DN. Fluid mechanics of vascular systems, diseases, and thrombosis[J]. Annu Rev Biomed Eng,1999,1:299-329
[26]Berger SA, Jou LD. Flows in stenotic vessels[J]. Annual Review of Fluid Mechanics,2000,32:347-382
[27]Taber LA. Biomechanics of cardiovascular development [J].Annu Rev Biomed Eng,2001,3:1-25
[28]C. P. Cannon. Management of acute coronary syndromes[J]. New Jersey: Humana Press Inc,1999
[29]Gertz SD, Roberts WC. Hemodynamic shear force in rupture of coronary arterial atherosclerotic plaques[J]. Am J Cardiol,1990,66(19):1368-1372
[30]Arroyo LH, Lee RT. Mechanisms of plaque rupture:mechanical and biologic interactions[J].Cardiovascular Research,1999,41(2):369-375
[31]Bank AJ, Versluis A, Dodge SM, et al. Atherosclerotic plaque rupture:a fatigue process[J]? Med Hypotheses,2000,55(6):480-484
[32]Jiang Y, Kohara K, Hiwada K. Association between risk factors for atheroscle-rosis and mechanical forces in carotid artery [J]. Stroke,2000,31(10):2319-2324
[33]Lee RT. Atherosclerotic lesion mechanics versus biology[J]. Z Kardiol,2000, 89 Supp12:80-84
[34]Dalin Tang,Chun Yang.Jie Zhang,Pamelak,et al.Local Maximal stress Hy-pothesis and Computational Plaque Vulnerability Index for Atherosclerotic Plaque Assessment [J].Annals of Biomedical Engineering,2005,33(12):1789-1801
[35]苏海军,张梅,张运.动脉粥样硬化斑块失稳破裂的力学模型[J].中国科学G辑,2004,34(2)：192-202
[36]A.H.奈弗,D.T.穆克.非线性振动[M].北京：高等教育出版社,1990,333-335
[37]Seemantini K. Nadkarni.Brett E.Bouma.Johannes de Boer.Guillermo J.Tearney.Evaluation of collagen in atherosclerotic plaques:the use of two co-herent laser-based imaging methods[J].Lasers Med Sci,2009,24:439-445