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

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD039676-02S1
Application #
6613061
Study Section
Geriatrics and Rehabilitation Medicine (GRM)
Program Officer
Nitkin, Ralph M
Project Start
2001-07-10
Project End
2006-06-01
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$73,500
Indirect Cost
Name
University of Georgia
Department
Miscellaneous
Type
Schools of Education
DUNS #
City
Athens
State
GA
Country
United States
Zip Code
30602
Erickson, Melissa L; Ryan, Terence E; Backus, Deborah et al. (2017) Endurance neuromuscular electrical stimulation training improves skeletal muscle oxidative capacity in individuals with motor-complete spinal cord injury. Muscle Nerve 55:669-675
Bickel, C Scott; Yarar-Fisher, Ceren; Mahoney, Edward T et al. (2015) Neuromuscular Electrical Stimulation-Induced Resistance Training After SCI: A Review of the Dudley Protocol. Top Spinal Cord Inj Rehabil 21:294-302
Young, Hui-Ju; Jenkins, Nathan T; Zhao, Qun et al. (2015) Measurement of intramuscular fat by muscle echo intensity. Muscle Nerve 52:963-71
Ryan, Terence E; Erickson, Melissa L; Young, Hui-Ju et al. (2013) Case report: endurance electrical stimulation training improves skeletal muscle oxidative capacity in chronic spinal cord injury. Arch Phys Med Rehabil 94:2559-61
Ryan, Terence E; Brizendine, Jared T; Backus, Deborah et al. (2013) Electrically induced resistance training in individuals with motor complete spinal cord injury. Arch Phys Med Rehabil 94:2166-73
Erickson, Melissa Lynn; Ryan, Terence E; Young, Hui-Ju et al. (2013) Near-infrared assessments of skeletal muscle oxidative capacity in persons with spinal cord injury. Eur J Appl Physiol 113:2275-83
Potter, Wm; Wang, L; McCully, Kk et al. (2013) Evaluation of a New 1H/31P Dual-Tuned Birdcage Coil for 31P Spectroscopy. Concepts Magn Reson Part B Magn Reson Eng 43:90-99
Ryan, Terence E; Southern, W Michael; Reynolds, Mary Ann et al. (2013) A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy. J Appl Physiol (1985) 115:1757-66
Ryan, Terence Edward; Southern, William Michael; Brizendine, Jared T et al. (2013) Activity-induced changes in skeletal muscle metabolism measured with optical spectroscopy. Med Sci Sports Exerc 45:2346-52
Ryan, Terence E; Erickson, Melissa L; Brizendine, Jared T et al. (2012) Noninvasive evaluation of skeletal muscle mitochondrial capacity with near-infrared spectroscopy: correcting for blood volume changes. J Appl Physiol 113:175-83

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