Inactivity or disuse as a result of immobilization, bed rest, non-weight bearing, or denervation causes many adaptive changes in skeletal muscle with muscular dysfunction as a final outcome. Loss of muscle mass or muscular atrophy is one of the most recognized consequences of disuse. Inactivity has also been shown to cause metabolic alterations in skeletal muscle, the most important being elevated basal inorganic phosphate (Pi). We have tracked 10 subjects through an 8 week period of cast immobilization of the lower leg followed by ten weeks of rehabilitation. For comparison of changes seen during rehabilitation, we have performed similar testing on 7 control subjects over a ten week period. Immobilization of the ten subjects resulted in skeletal muscle atrophy, an increase in basal inorganic phosphate and decreased force production. 31P NMR was used to show a 43% increase in basal inorganic phosphate in the atrophy group as compared with the control population. The maximum cross-sectional area of the triceps surae was seen to decrease as well. The extent of force loss was greater than the decrease in muscle cross-sectional area, meaning that the atrophic, disused muscle had become less efficient at producing force as compared to control subjects with similar muscle CSAs. Regression analysis of both atrophy and control measurements of MaxCSA versus Force proved statistically significant with the atrophy group generating lower forces at similar MaxCSAs (R2=0.55 in the atrophy group, and 0.70 in the control). Throughout recovery the muscular efficiency in the atrophy group was seen to increase approaching control values at the end of the rehab period. This was accomplished by an increase in Force, maximum CSA, and a decrease in basal inorganic phosphate. The change in muscular efficiency as a result of immobilization, where the extent of force loss and muscle function exceeded the decrease in muscle size suggests that there are other significant factors caused by immobilization that lead to an overall loss in muscul ar efficiency besides muscle atrophy. We believe elevated inorganic phosphate, along with a decrease in muscle size, to be an important contributor to decreased muscle function following immobilization.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR002305-15
Application #
6121064
Study Section
Project Start
1998-09-30
Project End
1999-09-29
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
15
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Pang, Henry; Bow, Cora; Cheung, Jason Pui Yin et al. (2018) The UTE Disc Sign on MRI: A Novel Imaging Biomarker Associated With Degenerative Spine Changes, Low Back Pain, and Disability. Spine (Phila Pa 1976) 43:503-511
Ferraro, Pilar M; Jester, Charles; Olm, Christopher A et al. (2018) Perfusion alterations converge with patterns of pathological spread in transactive response DNA-binding protein 43 proteinopathies. Neurobiol Aging 68:85-92
Ercan, Altan; Kohrt, Wendy M; Cui, Jing et al. (2017) Estrogens regulate glycosylation of IgG in women and men. JCI Insight 2:e89703
Xie, Long; Dolui, Sudipto; Das, Sandhitsu R et al. (2016) A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment. Neuroimage Clin 11:388-397
Yadav, Santosh K; Kathiresan, Nagarajan; Mohan, Suyash et al. (2016) Gender-based analysis of cortical thickness and structural connectivity in Parkinson's disease. J Neurol 263:2308-2318
Finkelstein, Joel S; Lee, Hang; Leder, Benjamin Z et al. (2016) Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. J Clin Invest 126:1114-25
Rosenbaum, Michael; Leibel, Rudolph L (2016) Models of energy homeostasis in response to maintenance of reduced body weight. Obesity (Silver Spring) 24:1620-9
Machida, Manabu; Panasyuk, George Y; Wang, Zheng-Min et al. (2016) Radiative transport and optical tomography with large datasets. J Opt Soc Am A Opt Image Sci Vis 33:551-8
Ban, H Y; Schweiger, M; Kavuri, V C et al. (2016) Heterodyne frequency-domain multispectral diffuse optical tomography of breast cancer in the parallel-plane transmission geometry. Med Phys 43:4383
Franklin, Teresa R; Jagannathan, Kanchana; Wetherill, Reagan R et al. (2015) Influence of menstrual cycle phase on neural and craving responses to appetitive smoking cues in naturally cycling females. Nicotine Tob Res 17:390-7

Showing the most recent 10 out of 414 publications