EFFECTS OF CHRONIC TRTMNT WI BUCINDOLOL HCL OR METOPROLOL TARTRATE

这项研究将比较特发性扩张型心肌病心衰患者右室(RV)心肌基因表达的变化与使用选择性b-阻滞剂布汀多洛治疗18个月后的室壁心肌表型变化。基因表达的变化将与RV和LV表型的变化以及肾上腺素能和肾素血管紧张素系统的行为有关。基因表达将通过定量反转录-聚合酶链式反应(RT-PCR)估计从RV心内膜心肌活检标本提取的总RNA中的mRNA丰度来测量；将通过磁共振成像(MRI)、超声心动图、放射性核素脑室造影术和心导管术来进行心室心肌表型分析；肾上腺素能活性将通过同位素方法直接在心脏中测量；肾素-血管紧张素系统的活性将通过测量心肌基因表达和激素标志物来评估。本研究的目的是确定与心力衰竭患者异常的室壁心肌表型相关的基因表达模式，并确定这些基因表达变化中的哪些是受b-肾上腺素和肾素-血管紧张素系统控制的。这些目标将通过比较本试验中研究的衰竭右心室和其他正在进行的研究中评估的未衰竭右心室的基因表达谱来实现。此外，还将评估接受非选择性b-阻滞剂布汀多洛或选择性b-阻滞剂美托洛尔治疗18个月的患者的基因表达变化与心肌表型变化的关系。

This study will compare the changes in right ventricular (RV) myocardial gene expression to alterations in ventricular myocardial phenotype in patients with heart failure from idiopathic dilated cardiomyopathy treated for 18 months with either the selective b-blocking agent bucindolol. Changes in gene expression will be related to changes in RV and LV phenotype, as well as to the behavior of the adrenergic and renin angiotensin systems. Gene expression will be measured by quantitative reverse transription-polymerase chain reaction (RT-PCR) estimation of mRNA abundance in total RNA extracted from RV endomyocardial biopsy specimens; ventricular myocardial phenotyping will be by magnetic resonance imaging (MRI), echocardiography, radionuclide ventriculography and cardiac catheterization; adrenergic activity will be directly measured in the heart by isotopic methods; and activity of the renin-angiotensin system will be assessed by measurements of myocardial gene expression and hormonal markers. The objectives of this study are to determine the patterns of gene expression associated with the abnormal human ventricular myocardial phenotype of myocardial failure, and to determine which of these changes in gene expression are under b-adrenergic and renin-angiotensin system control. These objectives will be pursued by comparing gene expression profiles in failing right ventricles studied in this trial vs nonfailing right ventricles assessed in other ongoing studies. In addition, the relationship of changes in gene expression to changes in myocardial phenotype in patients treated for 18 months with either the non-selective b-blocking agent bucindolol or the selective b-blocking agent metoprolol will be assessed.