The primary hypothesis for this study is that Myostatin and FHL-1 are important in the development of ICUAP and that changes in activity levels of muscle will modify the levels of expression and activity of these proteins.
ICUAP is an increasingly recognised clinical problem associated with significant morbidity and mortality. However the pathogenesis of the diseae is poorly understood and as yet no treatment exists. We believe that both myostatin and FHL-1 will be important in the development of this disease. This is based recent research and that both these proteins are likely to be regulated by sepsis and immobility (two major risk factors for ICUAP. There is evidence from invitro work that the two are likely to interact. We have designed an interventional trial to investigate the above hypothesis. Patients admitted to ICU and at risk of developing muscle wasting will be selected and receive electrical muscle stimulation of the quadriceps muscle for 1 week. Physiological measurements of peripheral and respiratory muscle strength and quadriceps size will be made pre and post intervention. And muscle biopsies, blood and urine collected from both legs pre and post intervention. The relevant molecular pathways can then be examined.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
13
Neuromuscular Electrical stimulation will be applied to one leg (randomly assigned).
National Heart and Lung Institute, Imperial College
London, United Kingdom
Change in muscle myostatin and FHL-1
Time frame: 1 week
Change in quadriceps cross sectional area
Time frame: 1 week
Change in quadriceps strength
Time frame: 1 week
Change in blood myostatin, miRNA and other markers of muscle breakdown
Time frame: 1 week
Changes in muscle protein synthesis and breakdown pathways as measured in the muscle biopsy samples.
Time frame: 1 week
Change in muscle breakdown and synthesis pathways as a factor of amount of muscle stimulation received.
Time frame: 1 week
Change in muscle phenotype and change in cross sectional area for individual fiber types
Time frame: 1 week
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