冠状动脉血栓形成的病理生理学——斑块破裂和斑块糜烂的作用

本文综述了冠状动脉粥样硬化血栓形成的病理生理学 ,斑块破裂和斑块糜烂在冠状动脉血栓形成中的作用 ,斑块破裂的机制和稳定斑块的治疗原则     

易损斑块的早期识别与干预

众所周知,急性冠状动脉综合征(ACS)的病理基础不是管腔的高度狭窄,而是动脉粥样硬化斑块发生破裂、糜烂或斑块内出血等诱发血栓形成,这种易于破损和触发血栓形成的斑块称为易损斑块.     

冠状动脉粥样硬化斑块组成成分与斑块破裂的关系

冠状动态粥样梗化斑块破裂是导致血栓形成引起急性缺血冠状动脉综合征的主要原因,斑块自身组成万分与斑块破裂的关系非常密切。本文概述了斑块组成成分在斑块破裂中所起的作用,并对易破斑块的识别和斑块破裂的预防作一简要叙述。     

急性冠状动脉综合征患者不稳定性斑块的血管内超声

目的观察急性冠状动脉综合征患者不稳定性斑块的血管内超声特征.方法 36例急性冠状动脉综合征患者和20例稳定型心绞痛患者进行冠状动脉造影及血管内超声检查.应用血管内超声分别观察比较冠状动脉内斑块的性质,同时测量冠状动脉病变部位及其参考部位的血管外弹力膜面积、管腔面积、斑块面积及管腔面积狭窄率,并计算斑块的偏心指数及血管重构指数.结果急性冠状动脉综合征患者中脂质斑块占77.8%(28/36),其中10例发生斑块破裂及血栓形成;稳定型心绞痛患者主要为纤维性斑块及混合性斑块,脂质斑块仅占10%(2/20),无斑块破裂及血栓形成.两组斑块的特征包括偏心性、外弹力膜面积、斑块面积及管腔面积狭窄率具有显著性差异.不稳定性斑块呈现明显的正性重构,占72.2%(26/36),而稳定性斑块主要表现为负性重构,占75%(15/20).结论血管内超声能够准确地识别动脉粥样硬化不稳定性斑块,为早期临床发现不稳定性斑块并预测斑块破裂奠定了基础.     

冠状动脉粥样硬化斑块破裂的细胞与分子生物学研究进展

近 10年来对冠状动脉粥样硬化斑块生物学和动脉粥样硬化斑块破裂触发的认识迅速加深 ,已明确几种使斑块失稳定的分子和细胞学机制。将来血管病理生理学的研究应以稳定易破裂动脉粥样硬化斑块以及减少动脉粥样硬化斑块破裂后血栓形成为方向。本文介绍了近年来动脉粥样硬化斑块破裂的细胞学及分子生物学研究进展。     

斑块侵蚀和钙化结节在急性冠状动脉综合征发病中的作用

冠状动脉内血栓形成是导致急性冠状动脉综合征（ACS）最常见的原因.而导致血栓形成的最常见机制为斑块破裂（PR）、斑块侵蚀和钙化结节（CN） [1-3].对心脏性猝死（SCD）的患者进行尸检发现,PR最常见[1,4],破裂倾向的斑块有几种组织学特征：（1）薄纤维帽（＜65 μm）;（2）大的脂质池;（3）纤维帽附近巨噬细胞聚集[4-5].同时也发现,很大一部分血栓形成的病变与潜在的斑块破裂并没有什么关系.van der Wal等[61发现在20例SCD患者中有60％发生PR,其余40％仅表现斑块侵蚀.Virmani等[1]对200例SCD患者进行研究发现,只有1/3存在PR,35％的血栓病变并没有PR.与血栓形成的病理相关性最低的是CN.由于缺乏易于识别的诊断形式,斑块侵蚀和CN在ACS患者中的发现率大大降低.本文将从临床表现、病理及影像学检查三方面对斑块侵蚀和CN进行描述,探讨其在ACS发病中的作用.     

冠状动脉血栓形成的病理生理学研究进展

通过对近年来冠状动脉血栓形成的资料分析,阐述了斑块的易损性及狭窄严重性,进一步对斑块破裂的原因启动因素、动果、稳定概念等病理生理学方面研究现状进行综述.     

超声评价颈动脉粥样硬化斑块稳定性进展

<正>冠心病和缺血性脑卒中的主要病因是动脉粥样硬化,动脉粥样硬化斑块因破裂或糜烂导致血栓形成,是严重心脑血管事件发生的主要机制。易于破裂并导致血栓形成的斑块,称之为"易损斑块"。颈动脉相对于冠状动脉而言,位置表浅且运动较少,因此,很多研究选用颈动脉作为研究易损     

基质金属蛋白酶与急性冠状动脉综合征的研究进展

随着对冠心病病例生理机制认识的不断深入，人们提出了急性冠状动脉综合征（acute coronary syndrome ACS）的新概念。ACS包括不稳定性心绞痛、急性心肌梗死和心脏性猝死。研究证实，冠状动脉粥样硬化斑块由稳定转为不稳定，继而破裂导致血栓形成是ACS最主要的发病机制。上述事件的发生，多数是由于狭窄并不十分严重的动脉粥样硬化斑块破裂、继发血栓形成造成的，虽然通过冠状动脉血运重建可纠正严重狭窄，但并不能改变动脉粥样硬化的生物学过程，斑块不稳定的问题仍然存在。因此，研究动脉粥样斑块破裂的机理，及寻找稳定斑块的有效治疗措施具有重要的临床意义。本文仅就基质金属蛋白酶与急性冠状动脉综合征的发病机制做一综述。     

易损斑块的诊断进展

急性冠状动脉综合征患者具有较高的发病率,预后较差,而冠状动脉内易损斑块破裂伴随血栓形成是其主要原因.因此早期正确诊断易损斑块,对于急性冠脉综合征的防治具有重大意义.现就易损斑块的诊断进展作一综述.     

Angioscopic and virtual histology intravascular ultrasound characteristics of culprit lesion morphology underlying coronary artery thrombosis

Although rupture of vulnerable plaque with subsequent thrombosis is the most common mechanism of acute coronary syndromes, a significant percentage of patients with acute coronary syndrome may not have plaque rupture. We used angioscopy and virtual histology intravascular ultrasound (VH-IVUS) to investigate the underlying morphology of coronary thrombosis. We correlated the angioscopic diagnosis of coronary thrombosis in 42 lesions (37 patients) with gray-scale and VH-IVUS findings of the underlying plaque. By angioscopy plaque rupture was present in 19 thrombotic lesions (45.2%), whereas 23 (54.8%) had no rupture. VH-IVUS findings comparing thrombotic lesions with to those without angioscopic plaque rupture were remarkably similar except that angioscopic nonruptures tended to have more necrotic core (NC) at the minimum lumen area site (22.2 ± 12.5% vs 16.3 ± 9.3%, p=0.09) and at the maximum NC site (32.7 ± 12.8% vs 25.0 ± 12.1%, p=0.053) compared to angioscopic ruptures. Furthermore, among 19 lesions with angioscopic plaque rupture, there were 11 VH thin-cap fibroatheromas (TCFAs; 57.9%); among 23 lesions without angioscopic rupture, there were 17 VH-TCFAs (73.9%, p=0.22). In conclusion, the similarity of VH-IVUS plaque composition (percentage of NC and percentage of VH-TCFA) in lesions with or without angioscopic plaque rupture suggest a spectrum of underlying morphologies to explain thrombosis in the absence of a ruptured plaque including classic erosions, small (and undetectable) plaque ruptures, and potentially unruptured TCFAs with superimposed thrombosis.     

冠状动脉CT成像与易损斑块

冠状动脉内斑块破裂或侵蚀所致的急性腔内血栓是急性冠状动脉综合征的主要原因。防止急性血栓形成成为了降低冠状动脉粥样硬化性心脏病病死率的唯一有效策略。斑块易破裂的冠状动脉病变与稳定斑块相比,存在不同的形态学改变。因此可以利用特殊的成像方法来识别这些易损斑块。亚毫米空间分辨率和图像质量优良的现代计算机断层扫描方法可以对冠状动脉斑块进行检测、分析和量化。斑块体积较大、低CT衰减、餐巾环征、正性重构以及点状钙化等与斑块容易破裂有密切关系。将冠状动脉斑块的形态学与功能特征等相结合,在未来有可能成为检测易损斑块的新方法。现将就多层螺旋CT与冠状动脉易损斑块的检测做一综述。     

The severity of coronary atherosclerosis at sites of plaque rupture with occlusive thrombosis

Atherosclerotic plaque rupture with superimposed thrombosis is recognized as the lesion causing greater than 90% of acute myocardial infarctions. To determine the severity of atherosclerosis at the site of plaque rupture, 184 coronary arteries from autopsies of 162 patients who died of acute myocardial infarction were studied. There were 102 men, 72 +/- 10 years old (mean +/- SD), and 60 women, 75 +/- 8 years old. All arteries were dissected from the heart, fixed, decalcified, cut at 2 to 3 mm intervals and processed routinely for histologic examination. A planimeter was used to measure artery, plaque, thrombus and luminal cross-sectional area at the site of plaque rupture with thrombosis in sections projected at x13.8 magnification. At the site of atherosclerotic plaque rupture with superimposed thrombosis, the degree of stenosis due to plaque was: 90 +/- 7% for the right (n = 67), 91 +/- 6% for the left anterior descending (n = 79) and 91 +/- 6% for the left circumflex (n = 38) coronary arteries. Plaque rupture in fatal acute myocardial infarction occurs at sites of severe narrowing (mean 91%, range 67% to 99%). Thus, plaque rupture with thrombosis is unlikely to cause the fatal acute myocardial infarction in patients with mild to moderate coronary stenosis.     

Clinical implications and mechanisms of plaque rupture in the acute coronary syndromes

Coronary atherosclerosis complicated by plaque rupture or disruption and thrombosis is primarily responsible for the development of acute coronary syndromes. Plaques with a large extracellular lipid-rich core, a thin fibrous cap due to reduced collagen content and smooth muscle density, and increased numbers of activated macrophages and mast cells appear to be vulnerable to rupture. Plaque disruption tends to occur at points at which the plaque surface is weakest and most vulnerable, which coincide with points at which stresses resulting from biomechanical and hemodynamic forces acting on plaques are concentrated. Reduced matrix synthesis as well as increased matrix degradation predisposes vulnerable plaques to rupture in response to extrinsic mechanical or hemodynamic stresses. Modification of endothelial dysfunction and reduction of vulnerability to plaque rupture and thrombosis may lead to plaque stabilization. These concepts have significant clinical implications that are just beginning to be explored and incorporated into clinical practice. This article reviews the mechanism of coronary atherosclerosis development and the pathophysiology of acute coronary syndromes to provide a framework for understanding how plaque passivation might be accomplished in clinical medicine.     

The role of plaque rupture and thrombosis in coronary artery disease

Atherosclerosis and its thrombotic complications are the major cause of morbidity and mortality in the industrialized world. The progression of atherosclerotic plaques in the coronary circulation is dependent on several risk factors. It is now clear that plaque composition is a major determinant of the risk of subsequent plaque rupture and superimposed thrombosis. The vulnerability of plaques to rupture is further determined by extrinsic triggering factors. Following rupture, the fatty core of the plaque and its high content of tissue factor provide a powerful substrate for the activation of the coagulation cascade. Plaque rupture can be clinically silent or cause symptoms of ischaemia depending on thrombus burden and the degree of vessel occlusion. In addition, plaque rupture and subsequent healing is recognized to be a major cause of further rapid plaque progression. This review looks at the mechanisms underlying the development and progression of atherosclerotic plaques, factors leading to plaque rupture and subsequent thrombosis and their clinical consequences. Finally, we speculate on targets for future research.     

Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi.

Ruptured atheromatous plaques were identified by step-sectioning technique as responsible for 40 of 51 recent coronary artery thrombi and 63 larger intimal haemorrhages. The degree of pre-existing luminal narrowing at the site of rupture was decisive for whether plaque rupture caused occlusive thrombosis or just intimal haemorrhage. If the pre-existing stenosis was greater than 90% (histologically determined) then plaque rupture nearly always caused occlusive thrombosis. Clearly indicating the primary role of plaque rupture in thrombus formation were the frequent finding of plaque fragments deeply buried in the centre of the thrombus and the nature of the thrombus at the site of rupture where it consisted predominantly of platelets. Thus, a severe chronic stenosis seems to be a prerequisite for occlusive thrombus formation, but the thrombotic process itself is triggered by an acute intimal lesion.     

Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction

OBJECTIVE—To evaluate the prevalence of plaque erosion as a substrate for coronary thrombosis.
DESIGN—Pathological study in patients with acute myocardial infarction not treated with thrombolysis or coronary interventional procedures.
PATIENTS—298 consecutive patients (189 men, mean (SD) age 66 (11) years; 109 women, 74 (8) years) dying in hospital between 1984 and 1996 from acute myocardial infarction, diagnosed by ECG changes and rise in cardiac enzymes.
MAIN OUTCOME MEASURES—Histopathological determination of plaque erosion as substrate for acute thrombosis; location and histological type of coronary thrombosis; acute and healed myocardial infarcts; ventricular rupture.
RESULTS—Acute coronary thrombi were found in 291 hearts (98%); in 74 cases (25%; 40/107 women (37.4%) and 34/184 men (18.5%); p = 0.0004), the plaque substrate for thrombosis was erosion. Healed infarcts were found in 37.5% of men v 22% of women (p = 0.01). Heart rupture was more common in women than in men (22% v 10.5%, p = 0.01). The distribution of infarcts, thrombus location, heart rupture, and healed infarcts was similar in cases of plaque rupture and plaque erosion.
CONCLUSIONS—Plaque erosion is an important substrate for coronary thrombosis in patients dying of acute myocardial infarction. Its prevalence is significantly higher in women than in men.


Keywords: plaque erosion; rupture; acute myocardial infarction     

Thrombosis and Fibrinolysis in Acute Myocardial Infarction

The development of coronary thrombosis in response to rupture of atherosclerotic plaques is the primary determinant of the evolution of stable atherosclerotic coronary disease to unstable ischemic syndromes and acute myocardial infarction. Activation of the tissue factor pathway of coagulation and adhesion of platelets are critical events in the initiation of thrombosis. However, subsequently, other factors may determine the extent of thrombosis by modulating the intensity of procoagulant and fibrinolytic activity. Marked procoagulant activity, attenuation of physiologic fibrinolytic activity, or both appear to be risk factors for myocardial infarction. The results of recent studies have provided considerable insight into potential mechanisms for thrombosis in response to rupture of atherosclerotic plaque and have identified potential novel antithrombotic interventions to inhibit the progression of coronary thrombosis.     

What an interventional cardiologist should know about the pathophysiology of acute myocardial infarction.

Basic knowledge of the sequence of cellular events that change the relative benign disease coronary atherosclerosis into a life-threatening acute coronary syndrome is of great importance for the interventional cardiologist in order to understand and choose the correct pharmacological and interventional management in patients with acute myocardial infarction. Plaque disruption, or fissuring, with superimposed thrombosis frequently complicates the course of coronary atherosclerosis. Small ruptures often remain clinically silent, whereas more extensive plaque rupture may lead to the development of unstable angina, acute myocardial infarction, and sudden cardiac death. The risk of plaque disruption depends more on plaque composition than on plaque size and stenosis severity. Major determinants of a plaque's vulnerability to rupture are: the size and consistency of the lipid-rich atheromatous core, the thickness of the fibrous cap covering the core, and inflammation and repair within the cap. The elevation of fibrinogen and C-reactive protein in patients with unstable angina may be markers of ongoing plaque inflammation. Both plaque vulnerability and rupture triggers are important for plaque disruption. The resultant thrombotic response, which is important for the clinical presentation and outcome, is in part determined by the reactivity of the circulating platelets and the balance between the fibrinolytic and coagulation systems. New ways of identification and treatment of the dangerous vulnerable plaques responsible for infarction and death and optimization of anti-thrombotic treatment are highly warranted in order to prevent and treat life-threatening coronary thrombosis.