Skeletal muscle plasticity, fitness and health after SCI

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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