CARVEDILOL TREATMENT FOR CHRONIC HEART FAILURE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 心力衰竭患者的长期β受体阻滞剂治疗与收缩功能增加、血流动力学改善、病理性重塑逆转、症状改善、住院治疗减少和死亡率降低相关。 β受体阻滞剂治疗的长期获益的临床证据是如此强大，以至于现在推荐在所有没有特定禁忌症的II级或III级心力衰竭症状患者中进行治疗。 本研究将探讨长期卡维地洛治疗是否会对卡维地洛的α 1-肾上腺素能受体阻断作用产生耐受性。我们将在17名心力衰竭受试者中测量苯丙氨酸（一种纯α 1-激动剂）输注对血压和心率的反应。 这些测量将在卡维地洛治疗开始前、卡维地洛剂量上调期间和卡维地洛连续治疗6个月后进行。 将测量收缩压升高20 mm Hg（PS20）所需的苯丙氨酸剂量和舒张压升高20 mm Hg（PD 20）所需的苯丙氨酸剂量。将计算并比较这些剂量下的剂量比。入组前，将采集血样，分析可能影响个体对苯肾上腺素反应的α 1-肾上腺素受体多态性。

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.