ISSN:0268-4705    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Recent advances in molecular genetics of arrhythmogenic right ventricular cardiomyopathy (ARVD) are reviewed. In particular, the finding of mutations in the gene coding for cardiac ryanodine receptor (hRYR2), both in patients affected with ARVD2 and in patients affected with catecholaminergic ventricular arrhythmias or with familial ventricular tachyarrhythmia, is discussed. Novel data support the hypothesis that apoptosis may be a key step in molecular pathogenesis of ARVDs. A series of studies on drugs with apparent protective effect against apoptosis in myocardial cells might open new perspectives in the therapeutic approach.

ISSN:0268-4705    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Pathogenesis of familial inherited arrhythmias is being progressively clarified thanks to the insights provided by molecular biology and by functional studies. Transmembrane or intracellular ion channel mutations have been identified in genetically determined forms of polymorphic ventricular tachycardia and sudden death such as catecholaminergic ventricular tachycardia, long QT syndrome, and Brugada syndrome. The role of molecular abnormalities in the genesis of monomorphic idiopathic ventricular tachycardias is less well defined, mainly because of the lack of a Mendelian pattern of inheritance. Interestingly, the presence of somatic mutations has been suggested as the mechanism for monomorphic ventricular tachycardia originating from the right ventricular outflow tract. The future goals for the application of molecular genetics to the management of cardiac arrhythmias will be to apply molecular genetics for a better risk stratification of affected individuals and to aim for the identification of gene-specific treatment of idiopathic ventricular tachycardia.

ISSN:0268-4705    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Genetic studies of families with inherited cardiac rhythm disturbances have established a molecular basis for ventricular arrhythmogenic disorders. Genes responsible for the long QT syndrome, Brugada syndrome, and polymorphic ventricular tachycardia have been identified. The elucidation of genetic defects responsible for more commonly occurring supraventricular rhythm disturbances have not been as forthcoming, with the exception ofSCN5Amutations known to cause conduction system disease. Recently, we identified the genetic cause of a familial arrhythmogenic syndrome characterized by ventricular preexcitation and tachyarrhythmias (Wolff–Parkinson–White syndrome), progressive conduction system disease, and cardiac hypertrophy. The causative gene was shown to be the &ggr;-2 regulatory subunit (PRKAG2) of AMP-activated protein kinase. The role of AMP-activated protein kinase in the regulation of the glucose metabolic pathway in muscle suggests that genetic defects inPRKAG2may induce a previously undescribed cardiac glycogenosis syndrome.

ISSN:0268-4705    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Coronary artery development is a complex vasculogenic process that begins shortly after heart looping. Coronary vasculogenesis is regulated by the myocardium, but is spatially and temporally dependent on the epicardium and its precursor, the proepicardial organ, for the provision of coronary vascular progenitor cells. Better understanding of the mechanisms of coronary artery development may clarify mechanisms of disease and suggest new potential therapies for disorders of the coronary vasculature.

ISSN:0268-4705    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

During the past decade, more than 100 mutations in 11 causal gene coding for sarcomeric proteins, the &ggr; subunit of AMP-activated protein kinase and triplet-repeat syndromes and in mitochondrial DNA, have been identified in patients with hypertrophic cardiomyopathy (HCM). Genotype–phenotype correlation studies show significant variability in the phenotype expression of HCM among affected individuals with identical causal mutations. Overall, causal mutations account for a fraction of the variability of phenotypes and genetic background, referred to as the modifier genes, play a significant role. The final phenotype is the result of interactions between the causal genes, genetic background (modifier genes), and probably the environmental factors. The individual modifier genes for HCM remain largely unknown, and a large-scale genome-wide approach and candidate gene analysis are needed. Current studies are limited to simple polymorphism association studies, which explore the association of functional single nucleotide polymorphisms in genes implicated in cardiac growth with the severity of the clinical phenotypes, primarily cardiac hypertrophy. Several potential modifier genes including genes encoding the components of the renin-angiotensin-aldosterone system have emerged. The most commonly implicated is an insertion/deletion polymorphism in the angiotensin-1 converting enzyme 1 gene, which is associated with the risk of sudden cardiac death and the severity of hypertrophy. Therapeutic interventions aimed at targeting the modifier genes have shown salutary effects in animal models of HCM. It has now recognized that modifier genes affect the expression of cardiac phenotype. Identification of the modifier genes will complement the results of studies of causative genes and could enhance genetic based diagnosis, risk stratification, and implementation of preventive and therapeutic measures in patients with HCM.

ISSN:0268-4705    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Echocardiography plays an important role in the diagnosis of patients with congestive heart failure (CHF). It determines the cause and readily provides a reliable noninvasive assessment of left and right ventricular function and filling pressures. This technique also has a tremendous potential in guiding therapy and tracking the clinical response. This review focuses on its prognostic power.

ISSN:0268-4705    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Levosimendan is a new inotropic and vasodilator agent. The inotropic effect is mediated by calcium concentration-dependent conformational changes in troponin C during systole leading to sensitization of the contractile apparatus to calcium ions. The vasodilator effect is mediated by opening potassium channels on vascular smooth muscle. It has a complex pharmacokinetic profile, with a long-acting metabolite that has hemodynamic effects persisting for approximately 1 week. Although it is absorbed orally, it has been developed only for intravenous use thus far. The hemodynamic effects are not reduced and may be enhanced in the presence of &bgr;-blockers, possibly an important attribute when dealing with exacerbation of heart failure caused by or in the presence of &bgr;-blockers. More patients with heart failure have participated in randomized controlled trials of levosimendan than of any other intravenous inotropic agent. Experience with its use after cardiac surgery is limited. Preliminary observations suggest that hemodynamic changes are associated with symptomatic benefit and a reduction in morbidity and mortality in patients with severe heart failure caused by left ventricular systolic dysfunction, compared with placebo in one study and dobutamine in another. Levosimendan may be the first inotropic agent that it is both safe and effective in altering clinical outcomes relevant for patients. Part of this benefit may be achieved because levosimendan allows other inotropic agents that may have adverse effects on patient outcome to be avoided. Further research is required to confirm whether levosimendan reduces mortality and morbidity compared with a placebo and when administered repetitively. If it does, it may become routine therapy for the treatment of severe heart failure.

ISSN:0268-4705    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Sick euthyroid syndrome is defined as the decrease of serum free triiodothyronine with normal free L-thyroxin and thyrotropin. Its appearance in patients with chronic heart failure is an indicator of severity. Exercise training through a wide variety of mechanisms reverses sick euthyroid syndrome (normalization of free triiodothyronine levels) and improves the ability to exercise. There is a connection during exercise among dyspnea, hyperventilation, fatigue, catecholamines, a decrease in the number and function of &bgr;-blocker receptors, and elevation of serum free triiodothyronine. It is not known whether sick euthyroid syndrome contributes to the development of heart failure or is only an attendant syndrome.

ISSN:0268-4705    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0268-4705    

出版商:OVID    

年代:2002

数据来源: OVID