Optimal Amino Acid Nutrition in Sepsis

摘要 脓毒症会对体内多个系统造成代谢应激。尽管公认的重要性是 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 在预防肌肉损失和肠道萎缩方面通常不成功。我们建议将以下方面的反应量化 肌肉、肠道和肝脏的蛋白质合成对特定配方的氨基酸的刺激作用 蛋白质合成。我们压倒一切的假设是，有一种独特的公式主要基于 最大限度刺激肌肉和肠道蛋白质合成的必需氨基酸(EaAs) 在维持肝脏蛋白质合成的同时，维持肝脏的蛋白质合成。 为了解决我们的一般假设，我们将解决以下具体目标： 具体目标1：检验猪脓毒症导致肌肉和肠道粘膜净破坏的假设 蛋白质；肠道精氨酸的减少；以及肝脏急性期蛋白的刺激 (以纤维蛋白原为代表)和白蛋白合成。 具体目标2：检验与特定氨基酸配方的反应有关的一系列假说。 这些配方是：在猪蛋白中发现的EAA和非EAA的平衡混合物；混合物 仅含EaS；以及EaS加12.5%瓜氨酸的混合物。 具体目标3：测试假设摄取基于EaaS的氨基酸混合物(无论是与或 不含瓜氨酸)会使血液酸度和尿素产量的变化最小 代表猪肌肉的完全平衡的EaS和非EaS混合物的量。 具体的目标将在一个慢性仪器化的猪模型上进行测试，该模型准备了留置导管以 启用跨肠道、肝脏和肌肉的采样。动静脉取材与稳定取血相结合 同位素方法将能够对所有终点进行量化。这项研究的结果应该会提供 为一种新的营养配方奠定基础，以专门支持脓毒症患者的器官和组织代谢。

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.