SKELETAL MUSCLE PROTEIN METABOLISM IN HEART FAILURE

点击翻译按钮获取中文摘要

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. The overall hypothesis put forth in this study is that heart failure patients are characterized by alterations in skeletal muscle protein metabolism that promote changes in the quantity and quality of skeletal muscle protein. The proposed studies will be performed on cachectic and non-cachectic heart failure patients and healthy controls. Cachectic patients will be characterized by weight loss and reduced skeletal muscle mass; whereas, non-cachectic patients will be characterized by weight stability and normal skeletal muscle mass. In this experimental model, alterations in skeletal muscle protein metabolism specific to cachectic heart failure patients represent possible mechanisms contributing to changes in skeletal muscle protein quantity and quality. Non-cachectic patients serve as a diseased control group and healthy volunteers as a non-diseased control group. The primary hypothesis to be tested is that increased muscle protein catabolism in the postabsorptive state and reduced protein anabolism in the postprandial state predispose heart failure patients to lose skeletal muscle protein. Skeletal muscle protein balance will be measured during postabsorptive (i.e. 24 hour fast) and simulated-postprandial (i.e., euglycemic hyperinsulinemia with concomitant hyperaminoacidemia) conditions using a combination of stable isotope tracer and forearm balance techniques. A secondary hypothesis to be tested is that skeletal muscle myosin heavy chain synthesis is reduced in heart failure patients compared to healthy controls. Skeletal muscle myosin heavy chain synthesis will be assessed by measuring the incorporation of stable isotopically-labeled leucine into skeletal muscle proteins.