MUSCLE PROTEIN RESPONSE: IMMOBILITY, INJURY & DEPLETION

在营养过程中获得正的身体氮平衡 分解代谢或创伤性疾病的补充并不能保证恢复 骨骼肌功能或质量。 正常收缩活动丧失 （不动性）可能会改变全身和肌肉对 在无压力的住院受试者中， 外周组织（肌肉）中的氨基酸仅代表一小部分 身体氮平衡分数。 在这样的主题中， 最大身体摄氧量的减少也被观察到， 住院和次极量运动会导致延迟恢复 肌肉蛋白质的平衡，尽管有足够的营养支持。 的 肌肉蛋白质平衡的动力学尚未得到很好的定义， 受伤后的患者，但可以预期，观察到的反应 在无压力的受试者中，创伤后应激反应会进一步受到干扰 条件，其中不动性是由神经体液和组织复合 伤害因素。 努力澄清瘦肉组织蛋白质的反应， 不动、受伤和营养不良， 恢复肌肉蛋白质的积累和功能可能会受益 许多患者正在接受营养支持。 该提案将评估 静脉营养支持对全身和肌肉的影响 蛋白质代谢，否则无压力，不活动或运动训练 受试者和活动受限的损伤后患者。 功能（氧气 吸收）能力和蛋白质代谢将在 营养补充，并在10天的完整期结束时， 非运动/每日次极量进食的静脉喂养 运动/吃饱的正常志愿者和患者。 系列评价 对这些方案的代谢反应将包括氮和矿物质 平衡、荷尔蒙反应和休息/运动能量消耗。 全身蛋白质动力学将来自稳定同位素输注 （15 N-甘氨酸和13 C-亮氨酸）。 骨骼肌蛋白质合成将是 通过肌肉蛋白的13 C-亮氨酸富集测定。 基端 将在饱食前后进行氨基酸通量， 与全身和肌肉蛋白动力学和清除率的相关性 推导 骨骼肌的功能和组成将由 直接测量跨膜电位差和经皮 肌肉活组织检查测定氨基酸和高能磷酸盐 浓度. 除了功能能力研究外， 技术也将应用于从轻度或 中度创伤性损伤，试图将全身和肌肉 对损伤和营养支持的具体反应。

The attainment of positive body nitrogen balance during nutritional repletion of catabolic or traumatic illness does not assure restoration of skeletal muscle function or mass. Loss of normal contractile activity (immobility) may alter both whole-body and muscle specific response to nutritional repletion in unstressed hospitalized subjects with intake of amino acids by peripheral tissue (muscle) representing only a small fraction of body nitrogen balance. In such subjects, a progressive reduction in maximal body oxygen uptake is also observed during hospitalization and a submaximal exercise bout results in delayed recovery of muscle protein balance despite adequate nutritional support. The dynamics of muscle protein balance have not been well defined in post-injury patients, but it may be anticipated that the response observed in unstressed subjects would be further disrupted by post-traumatic conditions, where immobility is compounded by neurohumoral and tissue injury factors. Efforts to clarify lean tissue protein responses to immobility, injury, and malnutrition in combination with earlier restoration of muscle protein accrual and function would likely benefit many patients undergoing nutritional support. This proposal will evaluate the impact of intravenous nutritional support upon whole-body and muscle protein metabolism in otherwise unstressed, inactive or exercise-trained subjects and activity-restricted, post-injury patients. Functional (oxygen uptake) capacity and protein metabolism will be evaluated prior to nutritional repletion and at the end of a 10-day period of complete intravenous feeding in non-exercised/repleted of daily submaximal exercise/repleted normal volunteers and patients. Serial evaluations of the metabolic responses to these regimens will include nitrogen and mineral balance, hormonal responses and resting/exercised energy expenditure. Whole-body protein kinetics will be derived from stable isotope infusions (15N-glycine and 13C-leucine). Skeletal muscle protein synthesis will be determined by 13C-leucine enrichment of muscle proteins. Basal extremity flux of amino acids will be performed before and after repletion, and correlations to whole-body and muscle protein kinetics and clearance derived. Skeletal muscle function and composition will be determined by direct measurement of transmembrane potential differences and percutaneous muscle biopsy for assay of amino acid and high energy phosphate concentration. Except for the functional capacity studies, the above techniques will also be applied to patients recovering from mild or moderate traumatic injury in an effort to correlate whole-body and muscle specific responses to injury and nutritional support.