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

Active myocarditis, a common precursor of dilated cardiomyopathy, is defined as myocardial inflammation and injury in the absence of ischemia. Many agents may cause myocarditis and the exact manifestation of the disease depends on the interplay between the inciting agent and host response. Widespread belief that myocarditis is an autoimmune disorder has led to the possible overuse of endomyocardial biopsy and immunosuppressive agents. Their use is further complicated by the observation that many patients improve with conservative management alone. The Myocarditis Treatment Trial was designed to address the role of immunosuppression in the treatment of myocarditis, define the natural history of the disease, and increase understanding of the immunologic mechanisms involved in the pathogenesis of the disease. Enrollment began in October 1986 and was completed in October 1990 with follow-up completed in 1991. The study failed to show a significant benefit for immunosuppressive agents. Conventional medical regimens should be used to alleviate symptoms and immunosuppressive agents should be reserved for patients with progressive deterioration and biopsy-proven disease.
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PMID:Implications of the Myocarditis Treatment Trial for clinical practice. 883 76

In the acute phase of Chagas' disease, the micropathology of the heart reveals a diffuse focal myocarditis, sometimes of a phlegmonous type and of an intensity not seen in any other inflammatory heart disease. Foci of myocytolytic necrosis and degeneration are seen microscopically with an intense mononuclear infiltrate associated with exudative phenomena and marked parasitism of myofibers. Abnormalities of the coronary microcirculation have been demonstrated in acute chagasic myocarditis as possible cause of transient ischemia consistent with the hypothesis of microvascular factor as a cause of the myocardial changes. Considering that the endothelium plays a key role as controller of the vessel tone regulation and vascular permeability, this investigation was carried out to study the structure of the endothelial lining of the thoracic and abdominal aorta obtained from Trypanosoma cruzi-infected rats in the acute septicemic phase by using scanning and transmission electron microscopy. The findings clearly demonstrate that the infected rats developed changes of the endothelial layer characterized by endothelial cell swelling and a few points of cell cytoplasm discontinuity appearing as holes exposing the subendothelial collagen usually associated with platelet-fibrin aggregates. These changes could disturb the generation of vasoactive substances, impairing the equilibrium between opposing forces. The exposition of the subendothelial collagen due to holes in the endothelial lining would favor platelet-fibrin aggregation. This way, the present results allow speculation that similar endothelial cells changes could be present in the microcirculation, reflecting a reduction in the protective role of the endothelium, participating in the genesis of vasospasm and platelet aggregation within coronary microvessels, and leading to the focal pathology in acute chagasic myocarditis.
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PMID:Aortic endothelial cell changes in the acute septicemic phase of experimental Trypanosoma cruzi infection in rats: scanning and transmission electron microscopic study. 931 44

Sudden cardiac death is the leading cause of death in industrialized countries. It is most frequently due to ventricular tachyarrhythmias occurring in the presence of coronary heart disease, but mechanisms linking sudden death to coronary atherosclerosis are still unclear. In autopsy studies of sudden death patients, the incidence of acute thrombotic coronary occlusions has varied between 4 and 74%. In over 600 consecutive patients with implantable cardioverter-defibrillators, we observed that appropriate shocks for electrogram-verified ventricular tachyarrhythmias was only very rarely followed by signs of acute myocardial infarction (< 3% of cases), not supporting the coronary occlusion theory of fatal arrhythmias. Cellular hypertrophy compensating for cell loss due to ischemia, intraventricular hypertension, cardiomyopathy, and myocarditis might play a role in arrhythmogenesis as evidenced by the fact that experimental induction and regression of hypertrophy are paralleled by changes in the inducibility of ventricular tachyarrhythmias. Atherogenic hyperlipidemias are associated with a systemic inflammatory response manifested by leukocytosis (lymphocytosis) and complex upregulations of proinflammatory-prothrombotic mediators, such as platelet-activating factor, cytokines, and hemostasis factors. The diurnal regulation of these mediators parallels circadian rhythms of coronary morbidity and mortality. Some upregulated mediators have been shown to exert direct arrhythmogenic effects. The potential contribution of hyperlipidemia-associated inflammatory factors to arrhythmogenesis is important, because it opens new molecular targets for antiarrhythmic drug design.
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PMID:Sudden cardiac death: still more questions than answers. 947 68

The heart is a tumor necrosis factor (TNF)-producing organ. Both myocardial macrophages and cardiac myocytes themselves synthesize TNF. Accumulating evidence indicates that myocardial TNF is an autocrine contributor to myocardial dysfunction and cardiomyocyte death in ischemia-reperfusion injury, sepsis, chronic heart failure, viral myocarditis, and cardiac allograft rejection. Indeed, locally (vs. systemically) produced TNF contributes to postischemic myocardial dysfunction via direct depression of contractility and induction of myocyte apoptosis. Lipopolysaccharide or ischemia-reperfusion activates myocardial P38 mitogen-activated protein (MAP) kinase and nuclear factor kappa B, which lead to TNF production. TNF depresses myocardial function by nitric oxide (NO)-dependent and NO-independent (sphingosine dependent) mechanisms. TNF activation of TNF receptor 1 or Fas may induce cardiac myocyte apoptosis. MAP kinases and TNF transcription factors are feasible targets for anti-TNF (i.e., cardioprotective) strategies. Endogenous anti-inflammatory ligands, which trigger the gp130 signaling cascade, heat shock proteins, and TNF-binding proteins, also control TNF production and activity. Thus modulation of TNF in cardiovascular disease represents a realistic goal for clinical medicine.
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PMID:Tumor necrosis factor in the heart. 953 Feb 22

In viral myocarditis, inflammation and destruction of cardiac myocytes leads to fibrosis, causing progressive impairment in cardiac function. Here we show the etiologic importance of serine elastase activity in the pathophysiology of acute viral myocarditis and the therapeutic efficacy of an elastase inhibitor. In DBA/2 mice inoculated with the encephalomyocarditis virus, a more than 150% increase in myocardial serine elastase activity is observed. This is suppressed by a selective serine elastase inhibitor, ZD0892, which is biologically effective after oral administration. Mice treated with this compound had little evidence of microvascular constriction and obstruction associated with myocarditis-induced ischemia reperfusion injury, much less inflammation and necrosis, only mild fibrosis and myocardial collagen deposition, and normal ventricular function, compared with the infected nontreated group.
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PMID:A serine elastase inhibitor reduces inflammation and fibrosis and preserves cardiac function after experimentally-induced murine myocarditis. 984 75

Severe necrotizing myocarditis associated with canine parvovirus type 2 (CPV-2) infection and diffuse leukoencephalomalacia was recognized in a 4-week-old mongrel puppy. The cardiac lesions were characterized by severe diffuse myocardial degeneration and necrosis with occasional massive mineralization and distinct intranuclear inclusion bodies. Immunohistochemical examination revealed the presence of CPV-2 antigens in both the cytoplasm and nuclei of the myocytes. In the white matter of the cerebrum, moderate to severe diffuse necrosis with diffuse infiltration of gitter cells and occasional diffuse mineral deposits were recognized symmetrically and bilaterally. In the meningocortical area of the cerebellum, there was mild focal hemorrhage and accumulation of hemosiderin-laden histiocytes. In addition to the absence of viral antigen (as judged by immunohistochemistry), neither viral inclusions nor other vascular lesions were identified in examined sections of brain. These findings suggest that the brain lesions were not induced by direct CPV-2 infection but were related to severe myocardial lesions producing prolonged hypoxia and/or ischemia.
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PMID:Subacute massive necrotizing myocarditis by canine parvovirus type 2 infection with diffuse leukoencephalomalacia in a puppy. 992 61

Abnormalities of the microvasculature are centrally involved in the pathogenesis of some forms of heart disease, but in others are consequences of it. Microvascular abnormalities may contribute to the progression of viral myocarditis and Chagas' disease. Focal abnormalities may occur early in some cardiomyopathies and do occur later in most types of myocarditis. The thickening of arteriolar walls in chronic hypertension is likely to contribute significantly to the impairment of coronary haemodynamics associated with adaptive ventricular hypertrophy and the consequent diminution of coronary reserve, increasing diffusion distances and failure of angiogenesis to compensate. However, the resulting myocyte necrosis stimulates inflammatory angiogenesis. When ischemic myocyte injury becomes irreversible there is a concomitant loss of capacity for reperfusion, the no-reflow phenomenon. Less severe temporary ischemia reduces the proportion of functional capillaries. Multiple mechanisms are involved in this microvascular stunning, including: reperfusion injury; leukocyte activation; adhesion and accumulation; and impaired endothelium-dependent vasodilation. Many of the microvascular changes are those of the inflammatory response to cell death and form part of a final common pathway in myocarditis, cardiomyopathy, cardiac hypertrophy and failure, and ischemic heart disease. Stimulation of angiogenesis prior to myocyte necrosis in hypertrophy and control of leukocyte activity in ischemic heart disease could minimize myocyte loss.
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PMID:Microvascular involvement in cardiac pathology. 999 May 24

Complex paracrine interactions exist between endothelial cells and cardiac myocytes in the heart. Cardiac endothelial cells release (or metabolize) several diffusible agents (e.g., nitric oxide [NO], endothelin-1, angiotensin II, adenylpurines) that exert direct effects on myocyte function, independent of changes in coronary flow. Some of these mediators are also generated by cardiac myocytes, often under pathological conditions. This review focuses on the role of NO in this paracrine/autocrine pathway. NO modulates several aspects of "physiological" myocardial function (e.g., excitation-contraction coupling; myocardial relaxation; diastolic function; the Frank-Starling response; heart rate; beta-adrenergic inotropic response; and myocardial energetics and substrate metabolism). The effects of NO are influenced by its cellular and enzymatic source, the amount generated, the presence of reactive oxygen species, interactions with neurohumoral and other stimuli, and the relative activation of cyclic GMP-dependent and -independent signal transduction pathways. The relative physiological importance of endothelium- and myocyte-derived NO remains to be established. In pathological situations (e.g., ischemia-reperfusion, left ventricular hypertrophy, heart failure, transplant vasculopathy and rejection, myocarditis), NO can potentially exert beneficial or deleterious effects. Beneficial effects of NO can result from endothelial-type nitric oxide synthase-derived NO or from spatially and temporally restricted expression of the inducible isoform, inducible-type nitric oxide synthase. Deleterious effects may result from (1) deficiency of NO or (2) excessive production, often inducible-type nitric oxide synthase-derived and usually with concurrent reactive oxygen species production and peroxynitrite formation. The balance between beneficial and deleterious effects of NO is of key importance with respect to its pathophysiological role.
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PMID:Paracrine and autocrine effects of nitric oxide on myocardial function. 1076 May 46

A spectrum of distinctive clinical presentations and electrocardiographic patterns have been recognized in neonates with ventricular arrhythmias. These may range from an incidental finding on a routine physical to cardiovascular collapse due to ventricular fibrillation. It has become increasingly important that the clinician considers ventricular tachycardia in the neonate with tachycardia when the QRS normal does not appear normal. In general, isolated premature ventricular depolarizations, couplets and non-sustained ventricular tachycardia in the absence of heart disease are associated with a favorable prognosis. Most of these arrhythmias tend to resolve during the first month of life. Conversely, sustained ventricular arrhythmias associated with ischemia, myocarditis or ventricular tumors are associated with a guarded prognosis. Treatment is based on the definition of associated cardiovascular disease, support of hemodynamic status and the judicious use of antiarrhythmic agents. Finally, there has been an increased recognition of idiopathic forms of ventricular tachycardia in the neonate which are associated with a favorable prognosis and may not require pharmacologic treatment. This review will discuss these arrhythmias in neonates, associated forms of cardiovascular disease, current treatment options and long-term prognosis.
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PMID:Ventricular arrhythmias. 1082 88

The echocardiographic examination is generally performed in patients with heart failure and it often gives a significant contribution to the differential diagnosis. Firstly, the evaluation of left ventricular pump function by measuring the ejection fraction (EF) can distinguish patients with heart failure into two different groups, with depressed or preserved EF. The most frequent causes of heart failure and depressed EF are coronary artery disease, idiopathic dilated cardiomyopathy (DCM) and hypertensive heart disease. Although the echocardiographic features of coronary artery disease versus idiopathic DCM may be similar, the demonstration of inducible ischemia at dobutamine echocardiographic test suggests the presence of significant coronary artery disease and may be useful in the selection of cases for coronary arteriography. The association of left ventricular hypertrophy, hypokinesis and, sometimes, significant dilation is compatible with hypertensive heart disease or end-stage hypertrophic cardiomyopathy. No useful echocardiographic findings can identify the patients with genetic DCM or affected by myocarditis from other cases with idiopathic DCM. Some advanced cases of right ventricular dysplasia/cardiomyopathy may show a biventricular involvement and mimic DCM; these patients are usually characterized at echo by predominant right ventricular dilation and multiple a-dyskinetic bulges in the absence of pulmonary hypertension. Very difficult to manage are the patients with significant left ventricular dysfunction and severe valvular heart disease (such as aortic stenosis or mitral regurgitation). According to the literature, the left ventricular systolic function is relatively preserved (EF > 40%) in 30-40% of patients with heart failure. In these cases a diastolic dysfunction may be hypothesized. Echo-Doppler evaluation can be helpful in the recognition of signs of increased left ventricular stiffness ("restrictive filling pattern") and of increased filling pressures. In the differential diagnosis one must first consider the most frequent heart disorders that may present with this clinical syndrome, coronary artery disease and hypertensive heart disease. Furthermore, other less common diseases characterized by heart failure due to predominant diastolic dysfunction are the following: hypertrophic and restrictive cardiomyopathies, infiltrative heart diseases, such as amyloidosis, and constrictive pericarditis. Restrictive cardiomyopathy is characterized by heart failure and preserved left ventricular EF in the absence of significant ventricular dilation and hypertrophy; typical, although not pathognomonic, echocardiographic features are atrial enlargement ad restrictive filling pattern. In distinguishing constrictive pericarditis from restrictive cardiomyopathy useful Doppler signs are the wide respiratory variability in flow velocities at mitral and tricuspid levels, due to increased ventricular interdependence caused by the presence of an abnormally rigid pericardium.
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PMID:[Contribution of echocardiography to the diagnosis of patients with chronic heart failure]. 1106 13


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