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(1/250) Global biventricular dysfunction in patients with asymptomatic coronary artery disease may be caused by myocarditis.

BACKGROUND: The causal role of asymptomatic critical coronary artery obstruction in patients presenting with severe global biventricular dysfunction but no evidence of myocardial infarction is uncertain. METHODS AND RESULTS: Among 291 patients aged >40 years undergoing a noninvasive (2-dimensional echocardiography) and invasive (catheterization, coronary angiography, and biventricular endomyocardial biopsy, 6 to 8 samples/patient) cardiac study because of progressive heart failure (New York Heart Association functional class III or IV) with global biventricular dysfunction and no history of myocardial ischemic events, 7 patients (2.4%; 7 men; mean age, 49+/-6.9 years) had severe coronary artery disease (3 vessels in 4 patients; 2 vessels in 1 patient, proximal occlusion of left anterior descending coronary artery in 2 patients). Left ventricular end-diastolic diameter and ejection fraction by 2-dimensional echocardiography were 73+/-10.5 mm and 23+/-6.5%, respectively, and right ventricular end-diastolic diameter and ejection fraction were 39+/-7 mm and 29+/-7.2%, respectively. Biopsy specimens showed extensive lymphocytic infiltrates with focal myocytolysis meeting the Dallas criteria for myocarditis in all patients (in 5 patients with and 2 patients without fibrosis). Cardiac autoantibodies were detected with indirect immunofluorescence in the serum of 2 patients with active myocarditis. The 2 patients with active inflammation received prednisone (1 mg. kg-1. d-1 for 4 weeks followed by 0.33 mg. kg-1. d-1 for 5 months) and azathioprine (2 mg. kg-1. d-1 for 5 months) in addition to conventional drug therapy for heart failure. At 8-month overall follow-up, cardiac volume and function improved considerably in immunosuppressed patients but remained unchanged in conventionally treated patients, of whom 1 died. CONCLUSIONS: Global biventricular dysfunction in patients with severe asymptomatic coronary artery disease and no evidence of previous myocardial infarction may be caused by myocarditis. Histologic findings may influence the treatment.  (+info)

(2/250) Cell death in acromegalic cardiomyopathy.

BACKGROUND: Prolonged untreated acromegaly leads to a nonspecific myopathy characterized by ventricular dysfunction and failure. However, the mechanisms responsible for the alterations of cardiac pump function remain to be defined. Because cell death is implicated in most cardiac disease processes, the possibility has been raised that myocyte apoptosis may occur in the acromegalic heart, contributing to the deterioration of ventricular hemodynamics. METHODS AND RESULTS: Ten acromegalic patients with diastolic dysfunction and 4 also with systolic dysfunction were subjected to electrocardiography, Holter monitoring, 2-dimensional echocardiography, cardiac catheterization, and biventricular and coronary angiography before surgical removal of a growth hormone-secreting pituitary adenoma. Endomyocardial biopsies were obtained and analyzed quantitatively in terms of tissue scarring and myocyte and nonmyocyte apoptosis. Myocardial samples from papillary muscles of patients who underwent valve replacement for mitral stenosis were used for comparison. The presence of apoptosis in myocytes and interstitial cells was determined by confocal microscopy with the use of 2 histochemical methods, consisting of terminal deoxynucleotidyl transferase (TdT) assay and Taq probe in situ ligation. Acromegaly was characterized by a 495-fold and 305-fold increase in apoptosis of myocytes and nonmyocytes, respectively. The magnitude of myocyte apoptosis correlated with the extent of impairment in ejection fraction and the duration of the disease. A similar correlation was found with the magnitude of collagen accumulation, indicative of previous myocyte necrosis. Myocyte death was independent from the hormonal levels of growth hormone and insulin-like growth factor-1. Apoptosis of interstitial cells did not correlate with ejection fraction. CONCLUSIONS: Myocyte cell death, apoptotic and necrotic in nature, may be critical for the development of ventricular dysfunction and its progression to cardiac failure with acromegaly.  (+info)

(3/250) Poverty and eosinophilia are risk factors for endomyocardial fibrosis (EMF) in Uganda.

OBJECTIVE: To determine the relative risks of socio-demographic, dietary, and environmental factors for endomyocardial fibrosis (EMF) in Uganda. METHOD: Unmatched case control study in Mulago Hospital, Kampala. Cases (n = 61) were sequential patients hospitalized with an echocardiographic diagnosis of EMF from June 1995 to March 1996. Controls (n = 120) were concurrent patients with other forms of heart disease (heart controls, n = 59) and subjects admitted for trauma or elective surgery (hospital controls, n = 61). All consenting subjects answered a structured questionnaire administered by trained interviewers. Complete blood counts, malaria films and stool examination for ova and parasites were performed. Questionnaires elicited information on home address, economic circumstances, variables concerned with environmental exposures and usual diet before becoming ill. RESULTS: After adjustment for age and sex, cases were significantly more likely than controls to have Rwanda/Burundi ethnic origins (P = 0.008). Compared with controls, cases had a lower level of education (P < 0.001 for heart controls and P = 0.07 for hospital controls), were more likely to be peasants (P < 0.001), and to come from Luwero or Mukono Districts (P = 0.003). After further adjustment for peasant occupation, cases were more likely than controls to walk barefoot (P = 0.015), consume cassava as their staple food (P < 0.001) and to lack fish or meat in dietary sauces (P = 0.02). Cases were more likely to exhibit absolute eosinophilia (P = 0.006). The effect of cassava diet was more marked in the younger age group, while the effect of eosinophilia was greater in adults. Socio-economic disadvantage is a risk for EMF. Absolute eosinophilia is a putative cause of EMF, a finding not explained by parasitism. CONCLUSION: Data indicate that relative poverty and environmental factors triggering eosinophilia appear to act in a geographically restricted region of Uganda in the aetiology of EMF.  (+info)

(4/250) Cardiac fibrosis and inflammation: interaction with hemodynamic and hormonal factors.

It is generally admitted that the pathogenesis of perivascular and interstitial cardiac fibrosis involves the response to two types of stimuli: a hormonal one, mainly involving the renin-angiotensin-aldosterone system and the more recently described endothelin system, and a hemodynamic stimulus, particularly high blood pressure. We propose in the present review a third step which, although not exclusive, interacts with the hormonal and hemodynamic ones, and involves inflammatory mechanisms. Indeed, hypertension is invariably associated with inflammatory cell infiltration either in the intimal part of large vessels or in the adventitial region of arterioles. This has led us to hypothesize that arterial wall cells may trigger the initial communications attracting inflammatory cells to the perivascular region. In this paper, we review the proinflammatory intercellular communications as well as the intracellular signaling which confer an inflammatory phenotype to arteries. In this context, the profibrogenic and proinflammatory effects of hemodynamic overload and peptidergic systems such as angiotensin II and endothelin are considered. The study of the inflammatory process is not without interest, especially in view of the strong modulating effect of the inflammatory mediators both on the inflammatory process itself and on the fibrotic process. The principal and the most potent mediators are reviewed. Finally, the hypothesis that the inflammatory process could be in reality an immune specific process is suggested.  (+info)

(5/250) Beta-adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic G(salpha) mouse.

Transgenic (TG) mice with cardiac G(salpha) overexpression exhibit enhanced inotropic and chronotropic responses to sympathetic stimulation, but develop cardiomyopathy with age. We tested the hypothesis that cardiomyopathy in TG mice with G(salpha) overexpression could be averted with chronic beta-adrenergic receptor (beta-AR) blockade. TG mice and age-matched wild-type littermates were treated with the beta-AR blocker propranolol for 6-7 months, starting at a time when the cardiomyopathy was developing but was not yet severe enough to induce significant cardiac depression (9.5 months of age), and ending at a time when cardiac depression and cardiomyopathy would have been clearly manifest (16 months of age). Propranolol treatment, which can induce cardiac depression in the normal heart, actually prevented cardiac dilation and the depressed left ventricular function characteristic of older TG mice, and abolished premature mortality. Propranolol also prevented the increase in myocyte cross-sectional area and myocardial fibrosis. Myocyte apoptosis, already apparent in 9-month-old TG mice, was actually eliminated by chronic propranolol. This study indicates that chronic sympathetic stimulation over an extended period is deleterious and results in cardiomyopathy. Conversely, beta-AR blockade is salutary in this situation and can prevent the development of cardiomyopathy.  (+info)

(6/250) Repetitive coxsackievirus infection induces cardiac dilatation in post-myocarditic mice.

The relation between mycarditis and dilated cardiomyopathy (DCM) is controversial. To clarify the pathogenic mechanism of these diseases, the present study examined the effect of repetitive inoculation with coxsackievirus B3 (CVB3) in post-myocarditic mice. Inbred 3-week-old A/J mice were inoculated intraperitoneally with CVB3 (Nancy strain; 2x10(4) plaque-forming units) and reinfected in the same manner with CVB3 at 40 weeks (3W+/40W+). All mice were killed at 42 weeks old. The weight of the hearts of the 3W+/40W+ group were significantly increased compared with those of the 3W-/40W+ group, and both the heart weight/body weight and lung weight/body weight ratios of the 3W+/40W+ group were also significantly increased over those of the 3W-/40W- group, although the levels of serum neutralizing antibody titers were significantly increased in the 3W+/40W+ group over the level of the other groups. No increase in inflammatory cell infiltration or fibrosis progression was observed in the 3W+/40W+ group relative to the 3W+/40W- group, but the second inoculation resulted in a significant left ventricular dilatation and in left and right ventricular free wall thinning (3.31+/-0.20 mm vs 2.61+/-0.19 mm, p<0.05; 0.54+/-0.09 mm vs 0.72+/-0.16 mm, p<0.05, respectively). The sarcomere length was also significantly increased in the 3W+/40W+ group compared with that of the other groups, as determined by electron microscopy. Degenerative or necrotic areas in the infected hearts were not stained with anti-mouse IgG antibody, but were stained, only in 3W+/40W+ mice, with anti-mouse IgM antibody. The concentrations of TNF-alpha in the hearts of the 3W+/40W+ group were increased significantly over those of the 3W+/40W- group. Repetitive CVB3 infection produced cardiac dilatation without inflammatory cell infiltration in post- myocarditic mice. Autoimmunity mediated by the circulation of certain antibodies (eg, antibodies against the CVB3 genome or a CVB3-related protein) may be part of the pathogenic mechanism for this phenomenon. Thus, repetitive virus infection might contribute to the pathogenesis of cardiac dilatation.  (+info)

(7/250) L-NAME-induced protein remodeling and fibrosis in the rat heart.

The aim of the present study was to determine whether NO deficiency itself or rather the elevation of systolic blood pressure is responsible for the protein and structural remodeling of the heart during hypertension induced by long-term treatment by nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Three groups of rats were investigated. The first group served as control. In the second group L-NAME was given in the dose of 20 mg/kg/day in the drinking water and in the third group L-NAME was given in the dose of 40 mg/kg/day during 4 weeks. While L-NAME treatment in both doses caused essentially the same increase in systolic blood pressure (SBP), NO synthase activity and cGMP concentration in the left ventricle decreased by 17% and 13%, respectively in the 20 mg/kg/day L-NAME group and by 69% and 27%, respectively in the 40 mg/kg/day L-NAME group. The protein profile of the left ventricle in both L-NAME groups was characterized by an increased concentration of metabolic proteins. Nevertheless, a significant increase in the concentration of pepsin-soluble collagenous proteins and the concentration of hydroxyproline in pepsin-insoluble collagenous proteins was found only in the group receiving 40 mg/kg/day L-NAME. The morphometric evaluation revealed a significant increase in myocardial fibrosis in both L-NAME groups. However, this was more pronounced in the 40 mg/kg/day L-NAME group. It is concluded that NO deficiency resulted in significant enhancement of fibrotic tissue growth in proportion to the administered L-NAME dose, while SBP was increased similarly in both L-NAME groups. Thus, NO deficiency rather than hemodynamic changes appears to be crucially involved in collagenous protein and fibrotic tissue changes of the left ventricle in hypertension induced by L-NAME.  (+info)

(8/250) Human chronic chagasic cardiopathy: participation of parasite antigens, subsets of lymphocytes, cytokines and microvascular abnormalities.

This article tries to demonstrate by new pathological findings (with the use of immunohistochemical technique and confocal laser microscopy) that chronic chagasic cardiomyopathy is a result of multiple factors involving myocarditis, immunodepression, severe fibrosis and microvessels dilatation and that all of these alterations are probably directly related with the presence of Trypanosoma cruzi parasites in the host associated with inadequate immunological response of the host.  (+info)