Skeletal muscle plasticity, fitness and health after SCI

脊髓损伤后骨骼肌的可塑性、健康和健康

基本信息

批准号：
6777378
负责人：
GARY A. DUDLEY
金额：
$ 8.67万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-10 至 2006-06-01
项目状态：
已结题

项目摘要

DESCRIPTION: (provided by applicant) Physical inactivity after spinal cord injury (SCI) leads to low exercise capacity and increased risk of cardio vascular disease mortality. Exercise conditioning, which moves an individual from the lowest to the next quintile for aerobic fitness, reduces mortality. Our long-term goal is to develop therapies that maintain cardiovascular health after SCI. We have shown that the major adaptation of skeletal muscle within 6 months of SCI is atrophy. We reversed this sarcopenia using our simplistic electromyostimulation (EMS) conditioning protocol. In contrast, it has been difficult to evoke hypertrophy in chronic patients. We hypothesize, therefore, that a meaningful increase in aerobic exercise capacity during functional electrical stimulation (FES) exercise will occur in short term but not chronic patients after EMS conditioning because the limitation in peak VO2 after SCI is a small active muscle mass. Metabolism/perfusion mismatch that results in fatigue and low force during EMS may explain the limited hypertrophy in chronic SCI. Lack of up regulation of endogenous growth factors, i.e., IGF1, which we have shown to occur in able-bodied individuals after EMS, may also limit muscle growth. We will also test these hypotheses. Patients within 4 to 8 months of or at least 3 years after complete SCI will be examined in studies with the following specific aims: 1) FES, which evokes dynamic knee extension exercise of m. quadriceps femoris, will be done to measure peak VO2 before and after EMS conditioning designed to evoke hypertrophy; 2) 12 weeks of EMS conditioning will be used to assess the hypertrophic capacity of m. quadriceps femoris. Coupled lengthening and shortening actions will be evoked. Fiber and whole muscle size will be assessed in biopsies of m. vastus lateralis and magnetic resonance images of m. quadriceps femoris; 3) Fatigue, blood flow and metabolism to perfusion matching of m. quadriceps femoris will be assessed. Force will be measured during EMS. Limb blood flow will be measured after cuff ischemia using duplex Doppler. Muscle oxidative capacity will be assessed using biopsies (metabolic enzymes) and near infrared spectrophotometry (state of oxygenation); and 4) Up regulation of component(s) of the skeletal muscle IGF-1 autocrine/paracrine system and responsiveness of satellite cells to IGF- 1 signaling will be measured after EMS of m. quadriceps femoris. These studies are significant. They assess pathophysiology (perfusion /metabolism mismatch and/or lack of up regulation of muscle growth factors), impairment (inability to evoke hypertrophy) and functional limitation (low aerobic exercise capacity) which lead to increased risk of cardiorespiratory disease mortality

描述：（由申请人提供）脊髓损伤后缺乏身体活动损伤（SCI）导致运动能力低下并增加心脏病风险血管疾病死亡率。运动调节，使人感动有氧健身从最低到下一个五分之一可以降低死亡率。我们的长期目标是开发维持心血管健康的疗法 SCI之后。我们已经证明骨骼肌的主要适应能力在 6 年内几个月的SCI是萎缩的。我们用简单的方法扭转了这种肌肉减少症电肌刺激 (EMS) 调理方案。相比之下，已经慢性患者很难引起肥大。因此，我们假设，功能期间有氧运动能力的显着提高电刺激（FES）运动会在短期内发生，但不会长期发生 EMS 调理后的患者，因为 SCI 后峰值摄氧量的限制是一小块活跃的肌肉。代谢/灌注不匹配导致 EMS 期间的疲劳和低力量可能解释了慢性患者的有限肥大 SCI。缺乏对内源性生长因子（即 IGF1）的上调调节，我们认为已证明在 EMS 后身体健全的个体中会发生这种情况，也可能会限制肌肉生长。我们还将测试这些假设。患者在 4 至 8 个月内或完成 SCI 后至少 3 年将在研究中进行检查以下具体目标：1) FES，引发动态膝关节伸展运动米。股四头肌，将在 EMS 之前和之后测量峰值 VO2 旨在引起肥大的调理； 2）12周的EMS调理将用于评估 m 的肥大能力。股四头肌。将引起耦合的延长和缩短动作。纤维和整体肌肉大小将通过 m 的活检进行评估。股外侧肌和磁力 m 的共振图像。股四头肌； 3）疲劳、血流量和 m 的代谢与灌注匹配。将评估股四头肌。将在 EMS 期间测量力。套上袖带后将测量肢体血流量使用双工多普勒进行缺血。肌肉氧化能力将使用以下方法进行评估活检（代谢酶）和近红外分光光度法（状态氧合）； 4) 骨骼肌 IGF-1 成分的上调自分泌/旁分泌系统和卫星细胞对 IGF-1 的反应信令将在 m 的 EMS 之后进行测量。股四头肌。这些研究是重要的。他们评估病理生理学（灌注/代谢不匹配和/或缺乏肌肉生长因子的上调）、损伤（无法引起肥大）和功能限制（有氧运动能力低）导致心肺疾病死亡风险增加