Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiography in patients with unstable angina or myocardial infarction with subtotal coronary occlusion often reveals eccentric stenoses with irregular borders, suggesting ruptured atherosclerotic plaques and thrombosis, as documented by angioscopy and at autopsy. We have simulated and studied these processes in an ex vivo perfusion chamber and in an in vivo swine model. Our results suggest that specific local factors at the time of plaque disruption influence the degree of thrombogenicity, the stability of the growing thrombus, and, therefore, possibly also the various clinical syndromes. These factors can be divided into two groups: local vessel wall-related factors and systemic factors with local action at the area of risk. These factors include the following. 1) Exposed substrate-related effects: Plaque rupture produces a rough surface and stimulates the development of occlusive thrombus in proportion to the degree of damage. 2) Fluid dynamics-related factors: The more severe the stenotic lesion after plaque rupture, the higher the local shear rate, resulting in enhanced platelet deposition and thrombus formation. 3) Vasoconstrictive effects: Vasospasm is an important contributor to the pathogenesis of ischemic heart disease. 4) Systemic factors: There is clinical and experimental evidence to suggest that various systemic factors at the time of plaque rupture may enhance thrombogenicity (i.e., levels of epinephrine, levels of serum cholesterol, impaired fibrinolysis). We have investigated the role of residual thrombus on the process of rethrombosis and found that a residual thrombus is a very thrombogenic surface that may significantly contribute to reocclusion even in heparinized blood. Using recombinant hirudin as a pharmacological tool in our flow studies, we observed that rethrombosis is partially caused by thrombin bound to fibrin in the original thrombus, because the effect is abolished by the specific thrombin inhibitor.
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PMID:Thrombus formation on ruptured atherosclerotic plaques and rethrombosis on evolving thrombi. 142 53

We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied the structural, immunohistochemical, and biochemical profile of plaques, with and without thrombus, including morphometry, immunophenotyping of inflammatory infiltrates, cytokine presence, and ultrastructural features. Critical coronary stenosis was almost the rule in both acute and chronic ischemic series (greater than 90%) whereas it reached 50% in control subjects. Thrombosis was principally characteristic of unstable-acute ischemic syndromes (unstable angina, 32%; acute myocardial infarction, 52%; cardiac sudden death, 26%) but was also found in chronic ischemia (stable angina, 12%; ischemic cardiomyopathy, 14%) and in control subjects (4%). Plaque fissuring without thrombus occurred in low percentages in lipid-rich, severe eccentric plaques in most series. Major differences were found between pultaceous-rich versus fibrous plaques rather than between plaques with or without thrombus. Pultaceous-rich plaques were frequent in sites of critical stenosis, thrombosis, and ulceration. Inflammatory infiltrates, i.e., T cells, macrophages, and a few beta cells, mostly occurred in lipid-rich, plaques unrelated to thrombus. In adventitia, infiltrates were a common finding unrelated to any syndrome. Necrotizing cytokines such as alpha-TNF were immunohistochemically detected in macrophages, smooth muscle, and intimal cells and detected by immunoblotting in 67% of pultaceous-rich plaques, either with or without thrombus. Immune response mediators such as IL-2 were also expressed in analogous plaques but in a minor percentage (50%-40%). Media were extensively damaged in severely diseased vessels with and without thrombus. Ultrastructural study showed that the fibrous cap was either highly cellular or densely fibrillar. Intimal injury with collagen exposure was often associated with platelet adhesion, whereas foamy cell exposure was not. In conclusion, investigated parameters were essentially similar in plaques, both with and without thrombus, whereas major differences were found between pultaceous-rich and fibrous plaques. Since platelets adhere to exposed collagen and not to foam cells, the type of exposed substrates could play a major role in thrombosis.
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PMID:Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. 189 66

Epidemiological surveys show the clear association of hypertension with an increased risk of developing ischaemic heart disease. One method of quantifying atherosclerosis is to measure, at necropsy, the percentage of the intimal surface of the coronary arteries or aorta which is occupied by raised plaques. When this is done in a large number of subjects the amount of intimal involvement in any particular geographical population correlates directly with the frequency of ischaemic heart disease. In all these populations, whether at a high risk or low risk of developing ischaemic heart disease, hypertensive subjects have a greater intimal involvement by plaques than normotensive subjects. Thus, the increased risk in hypertension is, in part, mediated by possession of more plaques. Plaque growth is due to the accumulation of lipid from the plasma, the ingress of monocytes with their conversion to lipid filled foam cells and the formation of collagen by smooth muscle cells. Hypertension may act by altering endothelial function to potentiate all these processes. Mechanical stress on endothelial cells will evoke the formation of growth factors for smooth muscle cells. Plaque growth in man is also episodic due to the formation of thrombi; a proportion of these episodes are symptomatic producing acute myocardial ischaemia but the majority are silent leading to sudden plaque expansion. Thrombi over plaques are either due to endothelial denudation injury or more commonly due to the tearing of the cap of a plaque leading to deep intimal injury. Necropsy surveys of control populations show that subjects with hypertension have a greater frequency of recent plaque tears compared with normotensive subjects.
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PMID:Hypertension and atherosclerotic (ischaemic) heart disease. 194 81

Unstable angina is a simple term used to describe a complex group of conditions with a heterogeneous pathogenesis and prognosis. In patients with cardiac disease, understanding pathogenetic mechanisms often influences decisions regarding prognosis and treatment. Potential causes for the development of acute myocardial ischemia include: 1. Extracardiac factors in the patient with severe coronary atherosclerosis. 2. Plaque disruption resulting in: a. Transient platelet aggregation in diseased vessels. b. Dynamic or intermittent coronary artery thrombosis. c. Hemorrhagic dissection into an atheromatous plaque. d. Abnormal constriction of a coronary artery. 3. Progression of atherosclerosis as a result of plaque "healing." It may not be possible to identify the appropriate mechanism responsible for unstable angina in every case but the clinician must attempt to do so since the selection of appropriate therapy for the individual patient depends on the mechanisms responsible for the symptoms.
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PMID:Unstable angina pectoris: pathogenesis and management. 268 40

Angina pectoris is a significant risk predictor in patients with atherosclerotic heart disease. The major complications are myocardial infarction, heart failure, and arrhythmias. Plaque rupture turns stable angina pectoris into acute coronary syndrome by provoking platelet aggregation and thereby thrombus formation. Verapamil significantly inhibits platelet aggregation and thrombus formation, which may be one of several reasons for the protective effect of verapamil on reinfarction in patients recovering from myocardial infarction. Ischemia may lead to left ventricular dilation and diastolic dysfunction, and thereby heart failure. In postinfarction patients intervention with verapamil significantly reduced the use of diuretics compared with placebo, indicating that anti-ischemic intervention may prevent heart failure. Ventricular arrhythmias are significantly associated with arrhythmic as well as non-arrhythmic death. The lack of preferential association of ventricular arrhythmias with arrhythmic death rather than nonarrhythmic death may imply that arrhythmias are provoked by ischemia. Antiarrhythmic intervention in postinfarction patients significantly increases death and arrhythmic events compared with placebo, especially in patients with residual ischemia. This may be due to a significant slowing of conduction during ischemia in patients treated with antiarrhythmic agents. In animal studies anti-ischemic agents prevent or suppress ventricular arrhythmias during ischemia, whereas traditional antiarrhythmic drugs have no effect or even worsen the arrhythmias, especially during episodes with elevated sympathetic activity. Verapamil significantly reduces plasma norepinephrine levels and the norepinephrine release during ischemia, whereby ventricular arrhythmias may be prevented. Also, supraventricular arrhythmias are significantly associated with myocardial ischemia and are prevented by verapamil. In patients with atherosclerotic heart diseases, angina pectoris is a significant risk predictor, but anti-ischemic intervention should be considered even in patients in whom the major problem is heart failure or arrhythmias.
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PMID:Anti-ischemic intervention as prognosis improvement in patients with coronary artery disease, with special focus on verapamil. 867 96

Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden coronary death. Therefore, for event-free survival, the vital question is not why atherosclerosis develops but rather why, after years of indolent growth, it suddenly becomes complicated by life-threatening thrombosis. Therefore, we have to focus on plaque composition and vulnerability to rupture and plaque thrombogenicity rather than on plaque size and stenosis severity. The risk for plaque disruption depends more on plaque vulnerability (plaque type) than on degree of stenosis (plaque size). Lipid-rich and soft plaques are more vulnerable and prone to rupture than collagen-rich and hard plaques. They are also highly thrombogenic after disruption because of high content of tissue factor. There seems to be three major determinants of a plaque's vulnerability to rupture: 1) the size and consistency of the lipid-rich atheromatous core, 2) the thickness of the fibrous cap covering the core, and 3) ongoing inflammation and repair processes within the fibrous cap. Lipid accumulation, cap thinning, lack of smooth muscle cells (smc), and macrophage-related inflammation destabilize plaques, making them vulnerable to rupture. In contrast, smc-related healing and repair processes stabilize plaques, protecting them against disruption. Plaque size or stenosis severity tell nothing about a plaque's vulnerability. Many vulnerable plaques are invisible angiographically due to their small size and compensatory vascular remodeling.
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PMID:Plaque pathology and coronary thrombosis in the pathogenesis of acute coronary syndromes. 1038 96

Coronary artery disease is the leading cause of death in much of the western world. Atherosclerotic plaques in the coronary arteries contribute to luminal obstruction leading to myocardial ischemia; however, abrupt coronary artery occlusion most frequently results from superimposition of a thrombus on a disrupted plaque, leading to the most serious clinical manifestations of coronary artery disease, ie, unstable angina, acute myocardial infarction, and sudden death. Plaque that have undergone disruption and, by inference, plaques at risk for disruption (vulnerable plaques), tend to demonstrate outward vessel remodeling, contain a large lipid core, thinned out fibrous cap, reduced collagen content, and increased inflammatory cell infiltration. Plaque stabilization through change in plaque composition may be responsible for reduced frequency of acute vaso-occlusive events observed with lipid and other risk-factor modifying interventions.
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PMID:Pathophysiology of coronary thrombosis: role of plaque rupture and plaque erosion. 1202 34

Despite crucial advances in our knowledge of the pathologic mechanisms and the availability of effective diagnostic and treatment modalities, coronary atherothrombosis remains the most frequent cause of ischemic heart disease. Plaque disruption with superimposed thrombosis is the main cause of unstable angina, myocardial infarction, and sudden death. New findings have recently introduced exciting concepts that could have major impact on the treatment of the atherothrombotic disease. We will discuss the mechanisms that lead to the development of atherothrombosis and those responsible for the acute coronary syndromes, as well as some of the concepts derived from in vivo observations using new imaging technologies (eg, high-resolution magnetic resonance imaging).
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PMID:New understanding, diagnosis, and prognosis of atherothrombosis and the role of imaging. 1264 40

Plaque disruption, which may be associated with some coronary risk factors, plays a key role in the development of acute coronary syndromes and progression of atherosclerosis. However, the clinical profile of asymptomatic plaque disruption in stable ischemic heart disease has not been well evaluated. The aim of the present study was to investigate the frequency and determinants of silent plaque disruption (SPD) in patients with stable ischemic heart disease using coronary angioscopy. Forty-one patients with stable angina or old myocardial infarction (OMI) without any complaints within 3 months were included in the present study. Angioscopy was successfully performed through 49 nonischemic related coronary arteries. The presence of SPD and coronary risk factors were recorded. Silent plaque disruption was found in 12 patients with stable ischemic heart disease (12/41, 29.3%), and the frequency of SPD in nonischemic related coronary arteries was 26.5% (13/49). A significantly higher frequency of SPD was noted in yellow plaques than in white plaques (35.3% versus 6.7%, P = 0.043). Overall, the independent clinical risk factors of SPD in nonischemic related coronary arteries were diabetes mellitus (P = 0.018; OR, 18.8209; 95% CI, 1.6525 to 214.3523) and hypertension (P = 0.0313; OR, 6.6485; 95% CI, 1.1850 to 37.3019). These results suggest silent plaque disruption was commonly observed in nonischemic related coronary arteries in patients with stable ischemic heart disease and its determinants were diabetes mellitus and hypertension.
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PMID:Angioscopic study of silent plaque disruption in nonischemic related coronary artery in patients with stable ischemic heart disease. 2117 12

Inflammation and oxidative stress play key roles in atherosclerotic plaque instability, and plaque rupture/erosion and subsequent thrombus formation constitute the principal mechanisms of total vessel occlusion and acute ST-elevation myocardial infarction (STEMI). Plaque disruption triggers the formation of initial platelet aggregates that grow in association with an increase in fibrin formation, leading to persistent coronary flow obstruction and blood coagulation. The fibrin network may trap large numbers of erythrocytes and inflammatory cells to form an erythrocyte-rich thrombus. In fact, previous clinical studies have shown that not only platelet-rich white thrombi, but also erythrocyte-rich red thrombi can be visualized using angioscopy in patients with acute coronary syndrome. Recently, the development of thrombus aspiration and distal protection devices has significantly improved the clinical outcomes of percutaneous intervention in STEMI patients and has enabled the evaluation of antemortem coronary artery thrombi. This is important because previous autopsy studies were unable to differentiate coronary thrombi responsible for myocardial ischemia from postmortem clots. Using frozen samples of aspirated thrombi and specific monoclonal antibodies, we investigated the cellular components of thrombi (platelets, erythrocytes, fibrin and inflammatory cells, such as myeloperoxidase-positive cells) and pathologically evaluated the relationships between erythrocyte-rich thrombi and inflammation, oxidative stress and clinical outcomes in STEMI patients. Therefore, this review article focuses on the efficacy of thrombus aspiration therapy and the components of aspirated intracoronary thrombi in STEMI patients and presents the results of recent studies regarding the relationship between the composition of aspirated intracoronary thrombi and clinical outcomes.
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PMID:Thrombus aspiration therapy and coronary thrombus components in patients with acute ST-elevation myocardial infarction. 2362 50


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