CARVEDILOL TREATMENT FOR CHRONIC HEART FAILURE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 心力衰竭的慢性β-受体阻滞剂治疗与收缩功能的增加、血流动力学的改善、病理重塑的逆转、症状的改善、住院时间的减少和死亡率的降低有关。β-受体阻滞剂治疗的长期益处的临床证据是如此之强，以至于现在建议对所有没有特定禁忌症的II级或III级心力衰竭症状的患者进行治疗。 本研究将调查慢性卡维地洛治疗是否会对卡维地洛的α1肾上腺素能受体阻断作用产生耐受性。我们将测量17名心力衰竭患者输注苯肾上腺素(一种纯的α1激动剂)后的血压和心率反应。这些测量将在卡维地洛治疗开始前、卡维地洛治疗期间和持续治疗6个月后进行。将测量使收缩压升高20 mm Hg所需的苯肾上腺素剂量(PS20)和使舒张压升高20 mm Hg所需的苯肾上腺素剂量(PD20)。在这些剂量下的剂量比率将被计算和比较。在注册之前，将采集血液样本来分析可能影响个体对苯肾上腺素反应的α1肾上腺素受体基因多态性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic beta-blocker treatment in heart failure is associated with increases in systolic function, improvement in hemodynamics, reversal of pathologic remodeling, improvement of symptoms, a reduction in hospitalization and a reduction in mortality. The clinical evidence for the long-term benefit of beta-blocker therapy is so strong that it is now recommended therapy in all patients with class II or III heart failure symptoms who do not have specific contraindications. This study will investigate whether tolerance to the alpha 1-adrenoceptor blocking effects of carvedilol develops with chronic carvedilol therapy. We will measure the blood pressure and heart rate response to phenylephrine (a pure alpha 1-agonist) infusions in 17 subjects with heart failure. These measurements will be made prior to the initiation of carvedilol therapy, during the uptitration of carvedilol, and after 6 months of continuous carvedilol therapy. The dose of phenylephrine required to increase systolic blood pressure by 20 mm Hg (PS20) and the dose of phenylephrine required to increase diastolic blood pressure by 20 mm Hg (PD20) will be measured. Dose ratios at these doses will be calculated and compared. Prior to enrollment, a blood sample will be obtained to analyze alpha 1-adrenoceptor polymorphisms that could affect the individual's response to phenylephrine.