Skeletal muscle plasticity, fitness and health after SCI

描述：（由申请人提供）脊髓损伤后缺乏体力活动 损伤（SCI）导致运动能力降低，增加心脏病风险 血管疾病死亡率。锻炼条件反射， 从最低到下一个五分之一的有氧健身，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，骨骼肌的主要适应性在6 脊髓损伤数月是萎缩。我们用我们简单的 电肌肉刺激（EMS）调节方案。相比之下， 难以引起慢性患者的肥大。因此，我们假设， 有氧运动能力的显著增加， 电刺激（FES）运动会在短期内发生，但不会长期发生 EMS预处理后的患者，因为SCI后峰值VO 2的限制是 一小块活跃的肌肉。代谢/灌注不匹配导致 EMS过程中的疲劳和低力可能解释了慢性心肌肥厚的局限性。 SCI.缺乏内源性生长因子的上调，即，IGF 1，我们 已经证明发生在身体健全的人后EMS，也可能限制肌肉 增长我们也将测试这些假设。4至8个月内的患者或 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，引起动态膝关节伸展运动 分枝将进行股四头肌，以测量EMS前后的峰值VO 2 旨在引起肥大的预处理; 2）12周EMS预处理 将用于评估M的肥大能力。股四头肌 将诱发耦合的延长和缩短动作。纤维和全 肌肉大小将在M的活组织检查中评估。股外侧肌和磁 共振成像的m。股四头肌; 3）疲劳，血流量和 代谢与灌注的匹配。将评估股四头肌。 将在EMS期间测量力。袖带后测量肢体血流量 多普勒显示缺血。肌肉氧化能力将使用 活组织检查（代谢酶）和近红外分光光度法（ 氧合）;和4）骨骼肌IGF-1的组分的上调 自分泌/旁分泌系统与卫星细胞对IGF- 1的反应性 将在EMS为m之后测量信令。股四头肌这些研究 意义重大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（不能 引起肥大）和功能限制（低有氧运动能力） 导致心肺疾病死亡风险增加

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