Optimal Amino Acid Nutrition in Sepsis

败血症的最佳氨基酸营养

• 批准号: 8059253
• 负责人: Nicolaas E Deutz
• 金额: $ 9.93万
• 依托单位: ARKANSAS CHILDREN'S HOSPITAL RES INST
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8059253
• 关键词: Acidity; Acute-Phase Proteins; Address; Albumins; Amino Acids; Animals; Arginine; Atrophic; Bacteria; Blood; Blood Vessels; Body part; Catabolism; Citrulline; Drug Formulations; Endotoxins; Equilibrium; Essential Amino Acids; Family suidae; Fibrinogen; Glutamine; Hepatic; Indwelling Catheter; Ingestion; Intake; Kidney; Liver; Metabolic; Metabolic Pathway; Metabolic stress; Metabolism; Methodology; Modeling; Mucous Membrane; Muscle; Muscle Proteins; Non-Essential Amino Acid; Nutrient; Nutritional; Nutritional Support; Organ; Permeability; Physiological; Plasma; Production; Protein Biosynthesis; Proteins; Role; Sampling; Sepsis; Series; Stress; System; Testing; Tissues; Urea; abstracting; base; design; falls; instrument; nutrition; oxidation; prevent; protein metabolism; response; septic; stable isotope

ABSTRACT Sepsis induces a metabolic stress on multiple systems in the body. Despite the well-recognized importance of supporting organ and tissue metabolism in sepsis with appropriate nutrition, current nutritional approaches are generally unsuccessful at preventing muscle loss and gut atrophy. We propose to quantify the response of protein synthesis in the muscle, gut, and liver to specific formulations of amino acids designed to stimulate protein synthesis. Our overriding hypothesis is that there is a unique formulation based primarily on essential amino acids (EAAs) that will maximally stimulate protein synthesis in muscle and gut mucosa, while maintaining protein synthesis in the liver. In order to address our general hypothesis we will address the following specific aims: Specific Aim 1: To test the hypothesis that sepsis in pigs induces a net breakdown of muscle and gut mucosal protein; a reduced production of arginine in the gut; and a stimulation of liver acute phase proteins (represented by fibrinogen) and albumin synthesis. Specific Aim 2: To test a series of hypotheses related to the responses to specific formulations of amino acids. Those formulations are: a balanced mixture of EAAs and non-EAAs in the profile found in pig protein; a mixture of only EAAs; and, a mixture of EAAs plus 12.5% citrulline. Specific Aim 3: To test the hypothesis that ingestion of mixtures of amino acids based on EAAs (either with or without citrulline) will minimize changes in blood acidity and urea production as compared to the corresponding amount of the complete balanced mixture of EAAs and non-EAAs representing pig muscle. The specific aims will be tested in a chronically instrumented pig model prepared with indwelling catheters to enable sampling across the gut, liver, and muscle. The combination of arteriovenous sampling and stable isotope methodology will enable quantification of all endpoints. The results of this study should provide the basis for a new nutritional formulation to specifically support organ and tissue metabolism in sepsis.

抽象的 败血症会引起体内多个系统的代谢应力。尽管公认的重要性 通过适当的营养支持器官和组织代谢，当前的营养方法是 通常无法成功防止肌肉损失和肠道萎缩。我们建议量化 肌肉，肠道和肝脏中的蛋白质合成，以旨在刺激的氨基酸的特定配方 蛋白质合成。我们的压倒性假设是，主要基于 必需的氨基酸（EAA），将最大程度地刺激肌肉和肠道中的蛋白质合成 粘膜，同时保持肝脏中的蛋白质合成。 为了解决我们的一般假设，我们将解决以下具体目标： 特定目的1：检验猪中败血症的假设诱导肌肉和肠粘膜的净分解 蛋白质;肠道中精氨酸的产生降低；和肝脏急性相蛋白的刺激 （由纤维蛋白原代表）和白蛋白合成。 特定目的2：测试与氨基酸特定配方反应有关的一系列假设。 这些配方是：在猪蛋白中发现的剖面中EAA和非AEA的平衡混合物；混合物 只有eaas;以及EAAS加12.5％瓜氨酸的混合物。 特定目的3：检验以下假设：摄入基于EAA的氨基酸的混合物（使用或 与相应的 代表猪肌肉的EAA和非AEA的完整平衡混合物的数量。 具体目的将在用留置导管制备的长期仪器猪模型中进行测试 在肠道，肝脏和肌肉中启用采样。动静脉采样和稳定的结合 同位素方法学将对所有端点进行量化。这项研究的结果应提供 新的营养制剂的基础，以特异性支持败血症的器官和组织代谢。