Peripheral Arterial Disease and Leg Muscle Metabolism

周围动脉疾病与腿部肌肉代谢

• 批准号: 6799560
• 负责人: LOIS A KILLEWICH
• 金额: $ 10.8万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6799560
• 关键词: aging; aminoacid; atherosclerosis; biopsy; clinical research; combination therapy; diet therapy; dietary aminoacid; dietary supplements; human old age (65+); human subject; human therapy evaluation; indocyanine green; leg; muscle metabolism; muscle proteins; patient oriented research; peripheral blood vessel disorder; plethysmography; protein biosynthesis; sarcopenia; stable isotope; aging; aminoacid; atherosclerosis; biopsy; clinical research; combination therapy; diet therapy; dietary aminoacid; dietary supplements; human old age (65+); human subject; human therapy evaluation; indocyanine green; leg; muscle metabolism; muscle proteins; patient oriented research; peripheral blood vessel disorder; plethysmography; protein biosynthesis; sarcopenia; stable isotope

DESCRIPTION (provided by applicant): DESCRIPTION (provided by applicant): As a vascular surgeon I treat atherosclerosis of leg arteries, known as peripheral arterial occlusive disease (PAOD). PAOD occurs when arteries to the leg become stenosed or occluded, reducing leg blood flow. Subjects experience calf muscle pain with walking, because although the blood supply is adequate to meet the metabolic demands of resting muscle, it is not adequate to meet the increased demands associated with exercise. Leg bypass surgery (femoro-popliteal bypass) increases leg blood flow, but alone does not improve walking abilities and functional status of elderly PAOD subjects. Effective treatment of PAOD will require identification and therapy for other adverse physiological conditions present in elderly PAOD subjects which contribute to their disability. Older subjects also develop sarcopenia, a condition in which muscle mass and function decline with age. At the University of Texas Medical Branch, Dr. Robert Wolfe, a nationally-known authority on leg muscle physiology, is studying sarcopenia in the elderly. He has developed a three-pool model of leg muscle protein metabolism, using infusion of stable isotopes and gas chromatography-mass spectroscopy methodology. He shown that nutritional supplementation (specifically, amino acids) increases leg muscle protein synthesis, and may therefore offer a method for counteracting the effects of sarcopenia. I was recruited to UTMB in 1999, and have formed a collaboration with Dr. Wolfe. In this study, I am proposing to investigate the relationship between PAOD and leg muscle protein synthesis in elderly subjects with PAOD. It is my hypothesis that reduced leg muscle blood flow associated with PAOD will limit the availability of amino acids to leg muscle, and thus further impair protein synthesis. Femoro-popliteal bypass surgery, by increasing blood flow, should increase delivery of amino acids to muscle and hence ameliorate the effects of sarcopenia. It is my ultimate hope that the combined interventions of bypass surgery and nutritional supplementation with amino acids can be used to improve overall functional status of these elderly Americans.

描述（由申请人提供）：描述（由申请人提供）：作为血管外科医生，我治疗了腿部动脉的动脉粥样硬化，称为外周动脉闭塞疾病（PAOD）。当腿部动脉被抑制或遮挡时，就会发生PAOD。受试者经历步行时会经历小腿肌肉疼痛，因为尽管血液供应足以满足静息肌肉的代谢需求，但它不足以满足与运动有关的增加的需求。腿旁路手术（股骨流动旁路）会增加腿部的血液流动，但单独的腿部血流并不能提高步行能力和老年PAOD受试者的功能状态。 PAOD的有效治疗将需要对老年PAOD受试者存在的其他不良生理状况进行鉴定和治疗，这有助于其残疾。 较老的受试者也会发展肌肉减少症，肌肉质量和功能随着年龄的增长而下降。在德克萨斯大学医学分公司，罗伯特·沃尔夫（Robert Wolfe）博士是腿部肌肉生理学的全国知名机构，正在老年人学习肌肉减少症。他使用稳定的同位素和气相色谱质量光谱法的输注，开发了腿部肌肉蛋白代谢的三池模型。他表明，营养补充（特别是氨基酸）会增加腿部肌肉蛋白的合成，因此可以提供一种抵消肌肉减少症的作用的方法。 我于1999年被招募到UTMB，并与Wolfe博士建立了合作。在这项研究中，我建议研究PAOD老年受试者PAOD与腿部肌肉蛋白质合成之间的关系。我的假设是，与PAOD相关的腿部肌肉血流减少将限制氨基酸对腿部肌肉的可用性，从而进一步损害蛋白质的合成。通过增加血流，应增加氨基酸向肌肉的递送，从而改善肌肉减少症的作用。我的最终希望是，旁路手术和补充营养补充氨基酸的综合干预措施可用于改善这些老年美国人的整体功能状况。