Novel Intervention to Influence Muscle Plasticity in Veterans
| Status: | Completed |
|---|---|
| Conditions: | Hospital, Orthopedic |
| Therapuetic Areas: | Orthopedics / Podiatry, Other |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 4/21/2016 |
| Start Date: | April 2011 |
| End Date: | December 2014 |
The loss of muscle contraction (paralysis) removes an important stimulus for maintenance of
overall health for individuals with complete spinal cord injury (SCI). Increased protein
catabolism (atrophy) limits important stresses to the skeletal system. Bone loss doubles the
risk of fracture and contributes to increased mortality in Veterans with SCI. Metabolic
syndrome and diabetes lead to heart disease in Veterans with SCI at higher rates than the
general population. Exercise methods to sustain muscle tissue, bone density, and metabolic
stability after SCI are lacking scientific justification. If left unchecked, the secondary
complications of SCI can be health limiting or even life threatening to Veterans with
paralysis. The importance of maintaining the health of the musculoskeletal system after SCI
has never been greater as a cure for paralysis may become a reality. Contemporary
rehabilitation interventions lack the ability to functionally load muscle tissue, quantify
the dose of load, stress the cardiovascular system, monitor the overall stresses during
daily exercise training, or offer portability to improve compliance with the exercise. The
long-term goal of this project is to establish the optimal dose of muscle and bone stress
during functional exercise in order to improve the health of Veterans with complete
paralysis. The practical outcome of this research is to offer a form of activity that is
feasible, portable, and grounded in sound scientific principles. The scientific goal is to
understand whether the dose of force generated in paralyzed muscle via evoked contractions
is critical to muscle atrophy/hypertrophy molecular pathways, physiologic performance, and
insulin sensitivity. The investigators will administer various doses of muscle force by
manipulating the frequency of electrical stimulation while keeping stimulation current (i.e.
muscle fiber recruitment) constant. Interestingly, no previous study has examined the dose
of muscle force necessary to trigger adaptations in protein synthesis/degradation pathways.
The investigators wish to discover the most effective method to maintain the molecular and
physiologic properties of paralyzed muscle. The investigators believe such a method will be
in urgent demand as a co-intervention with pharmaceutical strategies in post-SCI
rehabilitation.
overall health for individuals with complete spinal cord injury (SCI). Increased protein
catabolism (atrophy) limits important stresses to the skeletal system. Bone loss doubles the
risk of fracture and contributes to increased mortality in Veterans with SCI. Metabolic
syndrome and diabetes lead to heart disease in Veterans with SCI at higher rates than the
general population. Exercise methods to sustain muscle tissue, bone density, and metabolic
stability after SCI are lacking scientific justification. If left unchecked, the secondary
complications of SCI can be health limiting or even life threatening to Veterans with
paralysis. The importance of maintaining the health of the musculoskeletal system after SCI
has never been greater as a cure for paralysis may become a reality. Contemporary
rehabilitation interventions lack the ability to functionally load muscle tissue, quantify
the dose of load, stress the cardiovascular system, monitor the overall stresses during
daily exercise training, or offer portability to improve compliance with the exercise. The
long-term goal of this project is to establish the optimal dose of muscle and bone stress
during functional exercise in order to improve the health of Veterans with complete
paralysis. The practical outcome of this research is to offer a form of activity that is
feasible, portable, and grounded in sound scientific principles. The scientific goal is to
understand whether the dose of force generated in paralyzed muscle via evoked contractions
is critical to muscle atrophy/hypertrophy molecular pathways, physiologic performance, and
insulin sensitivity. The investigators will administer various doses of muscle force by
manipulating the frequency of electrical stimulation while keeping stimulation current (i.e.
muscle fiber recruitment) constant. Interestingly, no previous study has examined the dose
of muscle force necessary to trigger adaptations in protein synthesis/degradation pathways.
The investigators wish to discover the most effective method to maintain the molecular and
physiologic properties of paralyzed muscle. The investigators believe such a method will be
in urgent demand as a co-intervention with pharmaceutical strategies in post-SCI
rehabilitation.
Central Hypothesis: The investigators hypothesize that high muscle force induced via a
novel, portable, active standing intervention will increase muscle force properties, alter
gene expression for atrophy and fiber type pathways, and improve systemic insulin
sensitivity in Veterans with complete paralysis.
Aim 1: To determine the training effects of 3 tiers of quadriceps muscle force on muscle
physiological properties in Veterans with chronic paralysis from SCI.
Aim 2: To determine the training effects of 3 tiers of quadriceps muscle forces on muscle
mRNA for genes associated with atrophy and muscle fiber type in Veterans with complete
paralysis.
Aim 3: To determine the training effects of 2 tiers of compressive load induced by
quadriceps muscle forces on insulin sensitivity and markers of inflammation in Veterans with
SCI.
novel, portable, active standing intervention will increase muscle force properties, alter
gene expression for atrophy and fiber type pathways, and improve systemic insulin
sensitivity in Veterans with complete paralysis.
Aim 1: To determine the training effects of 3 tiers of quadriceps muscle force on muscle
physiological properties in Veterans with chronic paralysis from SCI.
Aim 2: To determine the training effects of 3 tiers of quadriceps muscle forces on muscle
mRNA for genes associated with atrophy and muscle fiber type in Veterans with complete
paralysis.
Aim 3: To determine the training effects of 2 tiers of compressive load induced by
quadriceps muscle forces on insulin sensitivity and markers of inflammation in Veterans with
SCI.
Inclusion Criteria:
- Inclusion criteria for all subjects will be upper motor neuron lesions between the
10th thoracic and the 7th cervical spinal levels. The completeness of the injury will
be verified by somatosensory evoked potentials.
Exclusion Criteria:
- Subjects will be excluded if they have pressure ulcers
- chronic infection
- lower extremity muscle contractures
- deep vein thrombosis
- recent limb fractures
- muscle metabolic disorders
- any comorbid disease known to affect bone metabolism (such as parathyroid
dysfunction)
- or if they are pregnant or plan to become pregnant.
- Subjects with distal femur trabecular bone mineral density less than 50 mg/cm3 will
be excluded from participation in quadriceps electrical stimulation training
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