Skeletal muscle plasticity, fitness and health after SCI

描述：(申请人提供)脊髓损伤后缺乏运动能力 损伤(SCI)导致运动能力降低和心脏病风险增加。 血管疾病死亡率。运动条件反射，它能移动一个人 从有氧健身的最低五分之一到下一个五分之一，降低死亡率。 我们的长期目标是开发维持心血管健康的治疗方法 在SCI之后。我们已经证明，骨骼肌的主要适应在6 几个月的脊髓损伤是萎缩的。我们用我们简单化的方法扭转了这种石棺减少症 肌电刺激(EMS)条件调节方案。相比之下，它一直是 慢性患者难以引起肥大。因此，我们假设， 在功能性运动期间有氧运动能力的显著增加 电刺激(FES)运动将在短期内进行，但不会长期进行 EMS预适应后的患者，因为脊髓损伤后的峰值VO2限制是 一小块活跃的肌肉块。代谢/灌流不匹配，导致 EMS过程中的疲劳和力量不足可能是慢性肥厚的原因 SCI。缺乏对内源性生长因子，即IGF1的上调，我们 已被证明发生在EMS后的健全个体，也可能限制肌肉 成长。我们还将检验这些假设。4至8个月或 在完成SCI至少3年后，将在与 具体目标如下：1)FES，唤起动态伸膝运动 对EMS前后股四头肌血氧分压峰值进行测量。 旨在诱发肥大的调节；2)12周的EMS调节 将用于评估股四头肌的肥大能力。 将会引发一系列的拉长和缩短动作。纤维和整体 肌肉大小将在股外侧肌活组织检查和磁力检查中评估。 股四头肌的磁共振图像；3)疲劳、血流和 将评估股四头肌代谢与血流灌注的匹配。 力将在EMS期间进行测量。袖带后将测量肢体血流量 双功多普勒检测脑缺血。肌肉氧化能力的评估将使用 活组织检查(代谢酶)和近红外分光光度测定法(状态 氧合)；以及4)上调骨骼肌胰岛素样生长因子-1的组成成分(S) 自分泌/旁分泌系统与卫星细胞对IGF-1的反应性 信号将在股四头肌EMS后进行测量。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(无能力 引起肥大)和功能受限(低有氧运动能力) 这会增加心肺疾病死亡的风险

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