Optimal Amino Acid Nutrition in Sepsis

摘要 脓毒症会对体内多个系统产生代谢应激。尽管公认的重要性， 通过适当的营养支持脓毒症的器官和组织代谢，目前的营养方法是 通常不能成功地防止肌肉损失和肠道萎缩。我们建议量化 蛋白质合成的肌肉，肠道，和肝脏的氨基酸的特定配方，旨在刺激 蛋白质合成我们最重要的假设是，有一个独特的提法，主要是基于 必需氨基酸（EAA），最大限度地刺激肌肉和肠道中的蛋白质合成 粘膜，同时维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： 具体目的1：检验猪败血症诱导肌肉和肠粘膜净分解的假设 蛋白质;肠道中精氨酸的产生减少;以及肝脏急性期蛋白质的刺激 （以纤维蛋白原为代表）和白蛋白合成。 具体目标2：检验与特定氨基酸制剂反应相关的一系列假设。 这些配方是：在猪蛋白中发现的EAA和非EAA的平衡混合物; EAA +12.5%瓜氨酸的混合物。 具体目标3：检验摄入基于EAA的氨基酸混合物（与或 与相应的相比，不含瓜氨酸）将最大限度地减少血液酸度和尿素产生的变化 代表猪肌肉的EAA和非EAA的完全平衡混合物的量。 将在使用留置导管制备的慢性仪器化猪模型中测试特定目的， 能够在肠道、肝脏和肌肉中取样。动静脉采样和稳定的 同位素方法将能够量化所有终点。这项研究的结果应提供 为专门支持脓毒症中器官和组织代谢的新营养制剂奠定了基础。

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.