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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Currently the problem of left ventricular remodelling in the early and late stages after myocardial infarction are under intense study. Studies of the role of remodelling of the left ventricle in patients with long-term arterial hypertension have been recently initiated. The purpose of this investigation was to study whether left ventricular remodelling is common for different primary myocardial disorders. The study population consisted of 212 patients with primary myocardial lesions (121 with dilated cardiomyopathy, 45 with chronic myocarditis and 46 with prolonged damage of the myocardium with alcohol; 196 male and 16 female, mean age 42.6+/-11.3 years) and 32 age matched normal subjects (24 male and eight female). Cardiac catheterization for ventriculography and coronary angiography was performed in all subjects for detection of left ventricular haemodynamics, including chamber volume and shape at end-systole and end-diastole. Worsening of heart failure was associated with a progressive enlargement of the left ventricle, with increases in end-systolic left ventricular wall stress, that lead to increases in left ventricular muscle mass, alteration of left ventricular geometry from a more ellipsoid to a more spherical shape and a progressive decrease of relative wall thickness index that reflects inadequate enlargement of the ventricular chamber in comparison with the increase in muscle mass. This process of left ventricular remodelling was common to all the primary myocardial disorders studied. Thus, regardless of the different etiological nature, most primary myocardial disorders show a similar left ventricular remodelling process suggesting common mechanisms for the development of chronic heart failure.
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PMID:Left ventricular remodelling: common process in patients with different primary myocardial disorders. 1021 79

Extracorporeal membrane oxygenation (ECMO) is used as circulatory support or bridge to transplantation in patients with severe left ventricular (LV) dysfunction. Left heart decompression is needed to reduce pulmonary edema, prevent pulmonary hemorrhage, and reduce ventricular distention that may aid in recovery of function. We reviewed our experience from November 1993 to December 1997 with 10 patients having severe LV dysfunction (7 myocarditis, 3 dilated cardiomyopathy) who required circulatory support with ECMO and who underwent left heart decompression with blade and balloon atrial septostomy (BBAS). Patients ranged in age from 1 to 24 years (median, 3 years). Indications for BBAS included left atrial/left ventricular distension (10), pulmonary edema/hemorrhage (9), or severe mitral regurgitation (2). BBAS was performed electively in eight patients and urgently in two patients. BBAS was performed while on ECMO in seven patients and pre-ECMO in three. A femoral venous approach was used in all patients. ECMO patients were fully heparinized. Transseptal puncture was required in nine patients while one patient had a patent foramen ovale. Blade septostomy was performed in all patients. Enlargement of the defect was then performed by stationary balloon dilation in nine and Rashkind balloon atrial septostomy in one. Balloon diameters ranged from 10 to 20 mm. Sequential balloon inflations were performed in some patients. Adequacy of the atrial septal defect (ASD) was confirmed by pressure measurement and echocardiography. Adequate left heart decompression was achieved in all patients. Pulmonary edema improved in nine of nine patients. Left atrial mean pressure fell from a mean of 30.5 mm Hg, (range, 12-50 mm Hg) to 16 mm Hg (range, 9-24 mm Hg). Left atrial to right atrial pressure gradient fell from a mean of 20 mm Hg pre-BBAS to 3 mm Hg post-BBAS. ASDs ranged in size from 2.5 to 8 mm (mean, 5.9 mm). Complications included needle perforation of the left atrium without hemodynamic compromise (one), ventricular fibrillation requiring defibrillation (one), and hypotension following BBAS which responded to volume infusion (two). Duration of ECMO ranged from 41 hr to 704 hr (mean, 294 hr). Seven patients survived and four patients had recovery of normal LV function. Of those who recovered, two had no ASD at follow-up while two ASDs are patent 14 days and 3 months post-BBAS. Three patients underwent successful cardiac transplantation. Three patients died, all of whom had multisystem organ failure with or without sepsis. A patent ASD was noted at transplant (three) or autopsy (two). No patient required a second BBAS. BBAS alleviates severe left atrial hypertension and pulmonary edema. In addition, BBAS avoids the potential bleeding complications of surgical left heart decompression. Stationary balloon dilation of the atrial septum is an effective alternative to Rashkind balloon septostomy in older patients. BBAS achieves left heart decompression that may permit recovery of LV function or allow extended ECMO support as a bridge to transplant.
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PMID:Blade and balloon atrial septostomy for left heart decompression in patients with severe ventricular dysfunction on extracorporeal membrane oxygenation. 1034 39

Charts of 180 patients (147 women, 33 men) with systemic lupus erythematosus (SLE) complicated by renal involvement were retrospectively analyzed from a series of 436 patients. Mean age at renal disease onset was 27 years. Thirty-six percent of the patients had renal involvement after diagnosis of lupus, for 30.7% of that group it was more than 5 years later. Renal involvement occurred more frequently in young male patients of non-French non-white origin. Patients with renal involvement suffered more commonly from malar rash, psychosis, myocarditis, pericarditis, lymphadenopathy, and hypertension. Anemia, low serum complement, and raised anti-dsDNA antibodies were more frequent. According to the 1982 World Health Organization classification, histologic examination of initial renal biopsy specimen in 158 patients showed normal kidney in 1.5% of cases, mesangial in 22%, focal proliferative in 22%, diffuse proliferative in 27%, membranous in 20%, chronic sclerosing glomerulonephritis in 1%, and other forms of nephritis in 6.5%. Distribution of initial glomerulonephritis patterns was similar whether renal involvement occurred before or after the diagnosis of lupus. Transformation from 1 histologic pattern to another was observed in more than half of the analyzable patients (those who underwent at least 2 renal biopsies). Nephritis evolved toward end-stage renal disease in 14 patients despite the combined use of steroids and cyclophosphamide in 12. Initial elevated serum creatinine levels, initial hypertension, non-French non-white origin, and proliferative lesions on the initial renal biopsy were indicators of poor renal outcome. Twenty-four patients died after a mean follow-up of 109 months from SLE diagnosis. Among our 436 patients, the 10-year survival rate was not significantly affected by the presence or absence of renal involvement at diagnosis (89% and 92%, respectively).
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PMID:Renal involvement in systemic lupus erythematosus. A study of 180 patients from a single center. 1035 47

National and international societies have issued guidelines on the management of heart failure: The European Society of Cardiology, WHO, ACC/AHA Task Force Report, US Department of Health and Human Services, German Society of Cardiology. The therapeutic approaches to heart failure have undergone considerable changes during the last few years. The guidelines have to be updated almost yearly due to new results from prospective randomized studies. Although an agreement could be reached with respect to general measures and drug treatment, no agreement on mechanical devices, pacemakers and surgical interventions has been reached. The basis for medical treatment of chronic heart failure depends on diuretics, digitalis, ACE inhibitors, and beta-blockers. Calcium antagonists and other positive inotropic drugs, other than digitalis, should be avoided as far as possible. Thiazides, loop diuretics and aldosterone antagonists are needed for acute and chronic treatment of heart failure, alone or in combination (diuretic resistant heart failure!). Digitalis glycosides are needed in patients with atrial fibrillation with a fast ventricular rate or atrial flutter and in patients with systolic dysfunction, large hearts and symptomatic failure class NYHA III and IV. However, digitalis does not convert atrial fibrillation to sinus rhythm. Today there is no question that ACE inhibitors improve the prognosis of all patients with heart failure in all stages, if ejection fraction is reduced. Therefore, most patients after myocardial infarction or after having experienced pump failure due to myocarditis or cardiomyopathy are treated with ACE inhibitors and diuretics. The beneficial effects of ACE inhibitors seem to be most pronounced the worse the situation is. Relative risk reductions (mortality!) between 10% and 40% have been published depending on the severity of symptomatic left ventricular dysfunction. Those patients with high absolute risk have more to gain than those with low risk for any given "risk reduction", of course. Recent studies also indicate that most high risk cardiac patients profit from ACE inhibitors even if pump function is normal (i.e., patients with coronary heart disease, diabetes mellitus, cerebral vascular disease, hypertension) (15). AT1 antagonists can substitute for ACE inhibitors, if the latter are not tolerated due to cough. Up to now, beta-blocking agents apart from diuretics seem to be the best investigated drugs in heart failure. Large controlled studies with bisoprolol, carvedilol and metoprolol in addition to diuretics, digitalis and ACE inhibitors convincingly yielded positive results in chronic left ventricular failure patients. Reduction of mortality by 35% and even of sudden cardiac deaths by 40% have been proven beyond doubt. Thus, heart failure patients today should also receive beta-blocking agents in all stages of the disease. In the era of controlled prospective studies (evidence-based medicine), physicians are well advised to use only drugs that have been proven beneficial in large controlled studies.
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PMID:The management of heart failure--an overview. 1119 49

The hemodynamic effects of endothelin (ET)-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Six weeks after immunization, survived Lewis rats (30/43 = 70%) were randomly allocated into five groups to be given 0, 0.3, 3, 30 and 60 mg/kg/day (groups F0, F0.3, F3, F30 and F60; each group, n = 4) of TAK-044 using an osmotic pump subcutaneously. Age-matched normal Lewis rats (n = 26) were also randomly divided into four groups to be given 0, 0.3, 3 and 30 mg/kg/day (groups N0, N0.3, N3 and N30; each group, n = 4). ET-1 concentrations in plasma and myocardium were measured, and immunohistochemical detection of ET-1 in the left ventricle from the remaining rats (groups F and N) was performed. After administration of TAK-044 for 7 days, 2, 4, 11, 21 and 42 ng/min ET-1 every 20 min was infused using a pump, and the change in mean arterial pressure of each group during the infusion was examined. The plasma and myocardial ET-1 concentrations were significantly higher in group F than group N (12.3 +/- 1.5 vs. 5.4 +/- 0.2 pg/ml and 426 +/- 31 vs. 98 +/- 6 pg/g tissue; both p < 0.01). Strong positive signals for ET-1 were found to be widely distributed in the left ventricular myocardium of both groups of rats. Although the ET-1-induced increase in the mean arterial pressure was abolished in group N30, the maximal dose of ET-1 produced a 34% increase in the mean arterial pressure in group F30. Even in group F60, ET-1-induced hypertension was blocked incompletely. These results indicate that the heart may be a major ET-1-producing organ, and a higher dose of ET-1 antagonist is needed to block the effect of ET-1 in rats with dilated cardiomyopathy.
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PMID:Acute effects of endothelin-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) in rats with dilated cardiomyopathy. 1120 20

Among the cardiomyopathies,--dilated cardiomyopathy (dcm), hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy--, dcm is the most frequent entity. Its prevalence in the United States amounts to 36 cases per 100,000 inhabitants, men being almost 3-fold more involved than women. The etiology of dcm is very heterogenous; 50% of the cases are due to idiopathic dcm whereas the other half comprises a broad spectrum of various etiologies such as myocarditis, ischemic heart disease, peripartal cardiomyopathy, hypertension, HIV infection, toxic cardiomyopathy and others. In 20 to 30% of the cases of idiopathic dcm a genetic transmission of the disease has been found. Another 20 to 30% of idiopathic dcm are associated with inflammatory and immunological phenomena. Infectious myocarditis with enteroviruses, especially with coxsackie-virus type B has been suggested to be an important trigger for an immune-mediated dcm. In both, familiar dcm and infection with coxsackie-virus B, an impairment of constituents of the myocardial cytoskeleton has been shown. This is regarded as a possible pathogenetic mechanism in the development of dcm.
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PMID:[Epidemiology-etiology of dilated cardiomyopathy]. 1126 35

Heart failure is not a single disease entity, but a syndrome with various causes, including hypertension, ischemic and congenital heart disease, cardiomyopathy, and myocarditis. Because of the multiple etiologies and secondary adaptations contributing to heart failure, the study of the cellular and molecular mechanisms underlying the development and progression of this syndrome has been rather challenging. Much has been learned about the remodeling processes in heart failure, which involve complex interactions among numerous mediators in signaling and regulatory pathways. The Human Genome Project and related projects have provided a preliminary database for a genome-wide analysis of complex polygenic disorders such as heart failure. With the aid of expressed sequence tag technology and microarray applications, both known and previously uncharacterized genes involved in the induction and regression of cardiac hypertrophy and its progression to heart failure can be analyzed simultaneously. Deciphering the complexity of sequence-structure-function relationships in heart failure is a goal for the future, and will require advances in structural biology, proteomics, and computational technology. In this review, we summarize the cellular and molecular aspects of heart failure, and how recent applications of genomic technologies have been successful in achieving a more complete portrait of gene expression in this pathologic state.
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PMID:Genomics and the pathophysiology of heart failure. 1130 73

Congestive heart failure may be produced by a variety of disorders, including dilated cardiomyopathy, hypertension, and ischemic heart disease. We have developed experimental models of these diseases, and found gene expressions of proinflammatory cytokines increased in the hearts of these animals. Various drugs for heart failure modulate the production of cytokines in experimental models of heart failure. Pimobendan, an inhibitor of phosphodiesterase III prolonged survival, attenuated inflammatory lesions, and decreased the production of cytokines and nitric oxide. Recent studies have shown that these inhibitory effects are due to inhibition of activation of NF-kappaB. In contrast, digitalis increased the production of cytokines and exacerbated myocarditis. Interleukin-10 prolonged survival, attenuated myocardial injury, and appears promising as a treatment of heart failure due to viral myocarditis. Endothelin-1 plays an important pathophysiological role in heart failure, and treatment with an endothelin antagonist had a cardioprotective effect in experimental models of heart failure.
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PMID:The role of inflammatory mediators in the failing heart: immunomodulation of cytokines in experimental models of heart failure. 1130 31

Pictures certainly are worth a thousand words in the case of the structure of the connective tissue skeleton of normal and diseased myocardium. This report reviews the connective tissue matrix of the normal human myocardial tissue and the pathological myocardial fibrosis in left ventricular hypertrophy due to chronic arterial hypertension in humans and in human chronic chagasic myocarditis. The myocardial connective tissue matrix was studied employing a cell-maceration method that removes the myocardial tissue non-fibrous elements, and leaves behind a non-collapsed matrix, thus allowing a better three-dimensional view. Such information extends our knowledge of the expression of interstitial myocardial fibrous tissue in normal hearts and in hypertensive left ventricular hypertrophy and chronic chagasic myocarditis. The progressive accumulation of interstitial collagen fibers in both chronic cardiac diseases may be expected to decrease myocardial compliance and disrupt synchronous contractions of the ventricles during systole, contributing to a spectrum of ventricular dysfunction that involve either the diastolic or systolic phase of the cardiac cycle or both. In hypertensive heart disease myocardial fibrosis can be also implicated in the genesis of ventricular dysrhythmias, possible causes of sudden death among chronic hypertensive patients. Regarding chronic chagasic myocarditis, myocardial fibrosis is probably implicated in the genesis of malignant ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation), major causes of sudden death among patients with chronic Chagas' heart disease. The collagen distribution could interfere on the electrical properties of the myocardium. Fibrosis can block the cardiac impulse that may recycle (re-entry) through an alternative route and could slow conduction. In addition, the thick collagenous septa encompassing muscle fiber bundles could interfere with lateral impulse conduction, which would favor re-entry. Moreover, the methodology used is a useful tool to study the spatial organization of the collagen fibrils of the myocardium under normal and pathological conditions.
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PMID:Connective tissue skeleton in the normal left ventricle and in hypertensive left ventricular hypertrophy and chronic chagasic myocarditis. 1143 16

Like in many other cell types, apoptosis can be induced by different stress in cells isolated from the cardiovascular system. The mitochondrial apoptotic pathway can be activated by serum deprivation, (9, 66) staurosporine treatment, (110) and oxidative stress. (14) The cytokine pathway is activated by TNF or Fas. (43, 52, 107) Immunohistochemical analysis of endomyocardial biopsies from patients with congestive heart failure, acute myocardial infarction, ischemic cardiomyopathies, and myocarditis, have led to the identification of apoptotic cardiomyocytes. (15 41, 74) Therefore, the pre-existing death program evidenced in isolated cardiomyocytes also may be activated in cardiomyopathies. Apoptosis also has been detected in vascular diseases, such as atherosclerosis, hypertension, and restenosis.49 It is likely that mitochondria, through permeabilization of their outer membrane, play a major role in many apoptotic responses leading to cardiomyocyte apoptosis. Elucidation of the mechanism whereby mitochondrial cell-death effectors are released in the cytosol should open the opportunity of developing compounds able to regulate the progression of apoptosis. The development of drugs acting on the mitochondrion may allow the prevention or the limitation of the seriousness of many cardiovascular diseases in which apoptosis has been detected.
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PMID:Involvement of mitochondria in apoptosis. 1178 13


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