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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The majority (greater than 75%) of major coronary thrombi are precipitated by a sudden rupture of the surface of an atherosclerotic plaque (plaque fissuring) causing platelet aggregation where thrombogenic subendothelial tissue has been exposed. Whether the thrombus remains mural and limited, just sealing the rupture, or evolves into an occlusive thrombus seems to depend on: (1) the amount and character of exposed thrombogenic material; (2) the actual thrombotic-thrombolytic equilibrium; and (3) local flow disturbances due to preexisting atherosclerotic stenosis. Thrombus formation may take place within the stenosis, where blood velocity and shear forces are highest, or it may take place or extend poststenotically, where flow separation, recirculation, and turbulence prevail. Platelet aggregation within the stenosis is responsible for the primary flow obstruction, but fibrin subsequently enmeshes the platelets and thus stabilizes the thrombus. Most thrombi have a layered structure, indicating an episodic growth that may alternate with thrombus fragmentation and peripheral embolization: thrombosis and thrombolysis are dynamic processes occurring simultaneously. If the platelet-rich thrombus at the rupture site evolves into an occlusive thrombus, the blood proximal and distal to the occlusion may stagnate and coagulate, giving rise to a secondarily formed red stagnation thrombosis consisting predominantly of erythrocytes held together by fibrin membranes. A ruptured plaque with a dynamic thrombosis superimposed (with or without spasm) seems to underlie the great majority of acute ischemic syndromes: unstable angina, acute infarction, and sudden death. The clinical presentation and the outcome depend on the severity and duration of ischemia: whether the obstruction is occlusive or nonocclusive, transient or persistent--modified by the magnitude of collateral flow.
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PMID:Coronary thrombosis: pathogenesis and clinical manifestations. 189 65

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

This study was designed to determine in patients with unstable angina whether specific electrocardiographic abnormalities associated with ischemia, the presence of coronary lesions consistent with thrombosis on angiography or the presence of recurrent ischemia reflects increases in thrombin activity as manifested by increased plasma concentrations of fibrinopeptide A. The concentration of fibrinopeptide A in plasma was increased to 6.7 +/- 3.1 nM for the group as a whole (n = 29). Increases were greater in the 17 patients who exhibited reversible ST segment shifts (10.2 +/- 5.2 nM) than in the 12 patients exhibiting reversible T wave abnormalities alone (1.6 +/- 0.2 nM) (p less than 0.01). Nine of the 17 patients with reversible ST segment shifts who underwent coronary angiography had lesions with morphologic characteristics consistent with atherosclerotic plaque complicated by thrombosis compared with only 2 of 9 patients with T wave changes only (p less than 0.05). Plasma concentrations of fibrinopeptide A were markedly elevated in 7 of the 11 patients in whom complex lesions were noted on angiographic examination. Thus, the occurrence of reversible ST segment shifts identifies a group of patients with unstable angina in whom ongoing thrombosis is likely and who may be particularly likely to benefit from antithrombotic therapy.
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PMID:Relation between ST segment shifts during ischemia and thrombin activity in patients with unstable angina. 189 62

Using the technology of his day, limited to direct observation and histological techniques, Fisher conclusively established the importance of the atherosclerotic carotid plaque in stroke. Recognizing the limits of his observations, he raised a number of questions as regards the degree of carotid disease necessary to adversely affect the brain and the effects of silent carotid occlusion. He also suggested the possible beneficial effects of revascularization. These questions have been addressed and in large part answered by PET. Thresholds of electrical activity and of cellular viability have been established both for cerebral blood flow and for oxygen metabolism. The effects of severe carotid stenosis have been found to be limited to the anterior border zone, where a decreased CBF and CBF to CBV ratio is seen in association with a trend towards rising OEF and declining CMRO2. The acute effects of a stroke and the passage of ischemia to infarction have been documented as they affect CBF, OEF, and CMRO2 in densely ischemic areas and in the penumbra region. An early pattern of elevated OEF in the face of diminished CBF is recognized and evolves into a later pattern of low OEF and CMRO2 characteristic of cell death. Silent carotid occlusion has been shown to produce widespread hypoperfusion and metabolic depression, the former improved by bypass, the latter not. Finally, the CBF to CBV ratio does not appear to be adequate in identifying patients who would benefit from EC-IC bypass, while an elevated preoperative OEF, an unusual event, does not clearly guarantee improved postoperative oxygen metabolism or the prevention of an ipsilateral stroke. Because the anterior border zone is selectively vulnerable to cerebral ischemia in patients with carotid stenosis, and since irreversible oxygen hypometabolism ensues once occlusion occurs, PET may be useful in identifying patients who may be at risk of further ischemic events should stenosis progress to occlusion. PET may also prove to be helpful in understanding the pathophysiology of ischemic complications associated with cerebral aneurysms and AVMs and may be a useful tool for deciding the timing of therapeutic intervention in these conditions.
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PMID:Physiologic studies of cerebral ischemia. 200 95

Patients with unstable angina and/or non-Q-wave infarction constitute a group that is at high risk for progression to acute myocardial infarction or sudden death. Furthermore, in spite of maximal medical therapy, a large fraction of these patients experience recurrent episodes of myocardial ischemia prompting surgical revascularization or coronary angioplasty. In prior studies of patients with unstable angina, the incidence of myocardial infarction within 1 month of hospitalization was 8-13%, and the incidence of death was about 4%. Between 3 months and 1 year after presentation, the cumulative rate of infarction or death increased to 10-14 and 8-10%, respectively. That is, most recurrent ischemic events occur within the first 3 months after the onset of symptoms. In the subset of patients with pain at rest or with electrocardiographic changes at the time of admission, the prognosis is even worse. The rate of myocardial infarction or death in such patients ranged between 14 and 21% during the first 3-4 months after onset of symptoms. Crossover to surgical therapy because of recurrent ischemic pain was also common, occurring in 30-50% of the patients at 3 months. Recent advances in understanding the pathophysiology of these two syndromes suggest that an aggressive antithrombotic regimen could be of great benefit in preventing progression to acute coronary occlusion and death. Pathologic investigations strongly suggested that plaque fissuring and subsequent overlying thrombosis were the major components in the process of unstable angina progressing to myocardial infarction and/or sudden death. This hypothesis has been substantiated by recent pathologic studies of patients who died shortly after the onset of unstable angina. Examination of the coronary arteries revealed not only plaque fissuring with superimposed layers of thrombus in the majority of the cases, but also evidence of distal thromboembolism from these foci. In vivo coronary arteriography in patients with unstable angina highlighted the progression of prior coronary stenoses, even to total occlusion, and the eccentric and irregular angiographic morphology of the ischemia-producing lesions. Furthermore, intracoronary thrombus is often seen at these sites, especially when arteriography is carried out soon after rest pain. These observations also suggested that plaque rupture may have occurred. Intraoperative angioscopy has revealed ruptured plaques in patients with progressive unstable angina, while those with rest pain had complicating thrombi. Patients with unstable angina also have biochemical evidence of activation of both the coagulation systems and platelets.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Insights into the pathogenetic mechanisms of unstable angina. 208 62

Myocardial ischemia has traditionally been related to increased demand, but recent data suggest that intermittent episodes of decreased supply are also important. This article discusses the phenomena underlying the factors that produce spontaneous (non-effort-related) ischemia. These include local arterial phenomena, arterial plaques, endothelial phenomena, neural phenomena, and circadian patterns. The clinical spectrum of myocardial ischemia can be viewed as an interplay among supply, demand, local arterial reactivity, and acute plaque disruption. In addition, neural phenomena and circadian patterns of multiple cardiovascular phenomena combine to make the coronary circulation susceptible to an increased concentration of events in the morning hours, around the time of awakening. With this extension of our understanding of myocardial ischemia, we have reasonable assurance that methods of treatment will advance significantly in the near future.
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PMID:Mechanisms of ischemia in coronary artery disease: spontaneous decrease in coronary blood supply. 220 96

Rupture of an atherosclerotic plaque associated with partial or complete thrombotic vessel occlusion is fundamental to the development of ischemic coronary syndromes. Plaques that produce only mild-to-moderate angiographic luminal stenosis are frequently those that undergo abrupt disruption, leading to unstable angina or acute myocardial infarction. Plaques with increased lipid content appear more prone to rupture, particularly when the lipid pool is localized eccentrically within the intima. Macrophages appear to play an important role in atherogenesis, perhaps by participating in the uptake and metabolism of lipoproteins, secretion of growth factors, and production of enzymes and toxic metabolites that may facilitate plaque rupture. In addition, the particular composition or configuration of a plaque and the hemodynamic forces to which it is exposed may determine its susceptibility to disruption. Exposure of collagen, lipids, and smooth muscle cells after plaque rupture leads to the activation of platelets and the coagulation cascade system. The resulting thrombus may lead to marked reduction in myocardial perfusion and the development of an unstable coronary syndrome, or it may become organized and incorporated into the diseased vessel, thus contributing to the progression of atherosclerosis. In unstable angina, plaque disruption leads to thrombosis, which is usually labile and results in only a transient reduction in myocardial perfusion. Release of vasoactive substances, arterial spasm, or increases in myocardial oxygen demand may contribute to ischemia. In acute myocardial infarction, plaque disruption results in a more persistent thrombotic vessel occlusion; the extent of necrosis depends on the size of the artery, the duration of occlusion, the presence of collateral flow, and the integrity of the fibrinolytic system. Thrombi that undergo lysis expose a highly thrombogenic surface to the circulating blood, which has the capacity of activating platelets and the coagulation cascade system and may lead to thrombotic reocclusion. Measurements aimed at reversing the process of atherosclerosis via cholesterol reduction and enhanced high density lipoprotein activity are encouraging. Active research is being focused on the development of new antithrombotic tools, such as inhibitors of thrombin, thromboxane, and serotonin receptor antagonists, and monoclonal antibodies aimed at blocking platelet membrane receptors or adhesive proteins. These compounds may prove useful when immediate and potent inhibition of the hemostatic system is desired. Intensive research is still needed in the areas of pathogenesis and therapeutic intervention in atherosclerosis.
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PMID:Atherosclerotic plaque rupture and thrombosis. Evolving concepts. 220 64

Acute mental stress may be a frequent trigger of transient myocardial ischemia, myocardial infarction and sudden cardiac death. In an experimental setting, the effect of mental stress on hemodynamics and left ventricular wall motion abnormalities (as detected by radionuclide ventriculography) was measured in 29 patients with exercise-induced myocardial ischemia. Seventy-five percent of the patients demonstrated mental stress-induced wall motion abnormalities. Patients frequently exhibited greater increases in peak systolic arterial pressure during mental stress than during exercise. Personally relevant mental stress is the most potent type of mental stress, both in terms of frequency and magnitude of ischemia. Most mental stress-induced ischemic episodes are clinically and electrocardiographically silent and occur at heart rates significantly lower than those seen during exercise. Both systolic and diastolic blood pressure increased during mental stress-induced ischemia, suggesting that increased myocardial oxygen demand plays a role in the pathophysiology of mental stress-induced transient ischemia. The significant magnitude and acute onset of this mental stress-induced blood pressure elevation may in some manner contribute to atherosclerotic plaque rupture. These findings may provide a pathophysiologic link to the epidemiologic association between mental stress and acute ischemic coronary events. A new ambulatory radionuclide detector that can concurrently monitor left ventricular ejection fraction and electrocardiographic ST-segment change may enhance the detection and evaluation of transient myocardial ischemia in ambulatory coronary patients.
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PMID:Mental stress as an acute trigger of ischemic left ventricular dysfunction and blood pressure elevation in coronary artery disease. 223 10

The phenomenon of transient myocardial ischemia is common in patients with stable coronary disease and appears to be due both to increases in myocardial demand and to episodic coronary vasoconstriction. The circadian variation of transient ischemic episodes closely parallels the circadian variation of acute coronary syndromes associated with plaque rupture, such as myocardial infarction and sudden death. These concordant temporal patterns of transient ischemia, myocardial infarction and sudden cardiac death probably represent independent manifestations stemming from the consequences of increased sympathetic activity.
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PMID:Triggers of transient myocardial ischemia: circadian variation and relation to plaque rupture and coronary thrombosis in stable coronary artery disease. 223 11

The clinical characteristics and coronary angiographic findings of 42 well-conditioned subjects with an acute ischemic event related to sport are reported. Five patients had unstable angina, 25 had acute myocardial infarction (AMI), and 12 were resuscitated victims of sudden ischemic death. Twenty-two events occurred during sport (group A) and 20 after sport (group B). There were two women and 40 men. The mean age was 46 years (range 25 to 65). Twelve out of 30 patients who smoked cigarettes had an adjunctive risk factor for coronary artery disease. Twelve others (28%) had no identifiable risk factor. Prodromal cardiac symptoms were detected in three patients (group A). Two patients had previous myocardial infarction (group B). Coronary angiography was performed acutely in 39 patients. The distribution of the ischemia-related coronary artery was comparable in both groups. The lesion morphology of 35 culprit coronary arteries was described as concentric in six patients and eccentric with regular borders (type I lesion) in 11 and irregular borders (type II lesion) in 18. Eccentric lesions consistent with ruptured plaques prevailed in both groups. Associated coronary artery disease was present in 10 patients. There was no relationship between the number of risk factors and the extent of diseased coronary arteries. Clinical characteristics and coronary angiographic findings of patients with unstable angina, AMI, and sudden death either during or after sport are similar and indicate a common pathogenesis. The probable mechanism of a coronary event related to sport is exercise-induced plaque rupture. In most instances such an event is unexpected and unpredictable. Identification of some subjects at risk is possible.
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PMID:Clinical characteristics and coronary angiographic findings of patients with unstable angina, acute myocardial infarction, and survivors of sudden ischemic death occurring during and after sport. 224 76


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