CONTRIBUTION OF ENERGY DEPLETION TO HUMAN HEART FAILURE

描述（申请人的描述逐字）：一个关键的未经测试的 人类心力衰竭的生化假说，特别强调的是， NHLBI心力衰竭研究特别强调小组（SEP）是 能量消耗对心力衰竭的影响。这一假设表明， 在充血性心力衰竭（CHF）中能量转移减少， 收缩功能ATP是维持正常的生化燃料， 收缩功能和磷酸肌酸（Pcr）迅速再生ATP， 肌酸激酶（CK）反应，是心脏的主要能量储备 组织中31P磁共振波谱（MRS）是唯一一种非侵入性的 直接研究心脏生化能量代谢的手段。的 研究人员开发了许多今天使用的31P MRS技术， 人心脏CK代谢物和最近能够检测的MRS技术 更微妙的能量转移限制。我们在这里提出一个结束 生物能量学和新型成像技术方面的专家与 心力衰竭临床医生首次将联合收割机 在生理条件下进行研究，并进行最新评估 收缩功能和强大的临床相关性，以评估是否 能量消耗存在并对人类心脏产生机械性影响 故障进展三个具体目标是：1。为了检验这一假设 CK能量储备系统的心肌代谢物浓度 与心力衰竭严重程度成比例降低，并预测其 进展2.为了评估心力衰竭的能量储备，我们将测试 假设心脏肌酸激酶能量储备对 正常人和衰竭人心肌能量需求的调节不同 心肌3.为了评估代谢干预，我们将检验假设 口服肌酸补充剂可以改善心肌能量， 从而改善收缩功能、症状和运动耐量， 慢性充血性心力衰竭患者。

DESCRIPTION (the applicant's description verbatim): A critical untested biochemical hypothesis of human heart failure, as specifically emphasized by the NHLBI Special Emphasis Panel (SEP) on Heart Failure Research, is the Contribution of Energy Depletion to Heart Failure. This hypothesis suggests that energy transfer is reduced in congestive heart failure (CHF) and may limit contractile function. ATP is the biochemical fuel that sustains normal contractile function and creatine phosphate (Pcr) rapidly re-generates ATP via the creatine kinase (CK) reaction and is the major energy reserve in cardiac tissues. 31P magnetic resonance spectroscopy (MRS) is the only non-invasive means for directly studying cardiac biochemical energy metabolism. The investigators developed many of the 31P MRS techniques used today to quantify human cardiac CK metabolites and recent MRS techniques capable of detecting more subtle limitations in energy transfer. We propose here a close collaboration among experts in bioenergetics and novel imaging techniques with heart failure clinicians to combine for the first time biochemical investigations under physiological conditions with state-of-the-art assessments of contractile function and robust clinical correlates to evaluate whether energy depletion is present and contributes mechanistically to human heart failure progression. The three specific aims are: 1. To test the hypothesis that the myocardial metabolite concentrations of the CK energy reserve system are reduced in proportion to heart failure severity and predict its progression. 2. To evaluate energy reserve in heart failure, we will test the hypothesis that the response of the cardiac creatine kinase energy reserve to modulations of myocardial energy demand differs in normal and failing human myocardium. 3.To evaluate a metabolic intervention, we will test the hypothesis that oral creatine supplementation can improve myocardial energetics and thereby improve contractile function, symptoms and exercise tolerance of patients with chronic congestive heart failure.