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Predictors of muscle hypertrophy responsiveness to electrically evoked resistance training after spinal cord injury

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Abstract

The purpose of the study was to identify potential predictors of muscle hypertrophy responsiveness following neuromuscular electrical stimulation resistance training (NMES-RT) in persons with chronic spinal cord injury (SCI). Data for twenty individuals with motor complete SCI who completed twice weekly NMES-RT lasting 12–16 weeks as part of their participation in one of two separate clinical trials were pooled and retrospectively analyzed. Magnetic resonance imaging (MRI) was used to measure muscle cross-sectional area (CSA) of the whole thigh and knee extensor muscle before and after NMES-RT. Muscle biopsies and fasting biomarkers were also measured. Following the completion of the respective NMES-RT trials, participants were classified into either high-responders (n = 8; muscle CSA > 20%) or low-responders (n = 12; muscle CSA < 20%) based on whole thigh muscle CSA hypertrophy. Whole thigh muscle and knee extensors CSAs were significantly greater (P < 0.0001) in high-responders (29 ± 7% and 47 ± 15%, respectively) compared to low-responders (12 ± 3% and 19 ± 6%, respectively). There were no differences in total caloric intake or macronutrient intake between groups. Extensor spasticity was lower in the high-responders compared to the low-responders as was the dosage of baclofen. Prior to the intervention, the high-responders had greater body mass compared to the low-responders with SCI (87.8 ± 13.7 vs. 70.4 ± 15.8 kg; P = 0.012), body mass index (BMI: 27.6 ± 2.7 vs. 22.9 ± 6.0 kg/m2; P = 0.04), as well as greater percentage in whole body and regional fat mass (P < 0.05). Furthermore, high-responders had a 69% greater increase (P = 0.086) in total Akt protein expression than low-responders. High-responders also exhibited reduced circulating IGF-1 with a concomitant increase in IGFBP-3. Exploratory analyses revealed upregulation of mRNAs for muscle hypertrophy markers [IRS-1, Akt, mTOR] and downregulation of protein degradation markers [myostatin, MurF-1, and PDK4] in the high-responders compared to low-responders. The findings indicate that body composition, spasticity, baclofen usage, and multiple signaling pathways (anabolic and catabolic) are involved in the differential muscle hypertrophy response to NMES-RT in persons with chronic SCI.

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Abbreviations

BMI:

Body mass index

CSA:

Cross-sectional area

MRI:

Magnetic resonance imaging

NMES:

Neuromuscular electrical stimulation

RT:

Resistance training

SCI:

Spinal cord injury

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Acknowledgements

We would like to thank the participants who gave their time and energy to our study. We would also like also to thank the MRI technicians in the Radiology department for their work in obtaining the images as well as the nurses in the Clinical Research Center of MCV hospital for their valuable time and effort. We also thank Hunter Holmes McGuire Research Institute and Spinal Cord Injury Services and Disorders for the use of their facilities in our human research trials.

Funding

This study was supported by the DoD-CDMRP (W81XWH-14-SCIRP-CTA), by VA Rehabilitation Research and Development Service award B-2020-C and by the James J Peters VA Medical Center. The funding agencies had nothing to do with the design of the study and data collection, analysis, and interpretation of data or in writing the manuscript. The work reported herein does not represent the views of the US Department of Veterans Affairs or the US Government.

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Authors and Affiliations

  1. Spinal Cord Injury and Disorders Service, Central Virginia VA Health Care System, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA

    Ashraf S. Gorgey, Jacob A. Goldsmith & Refka E. Khalil

  2. Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA

    Ashraf S. Gorgey

  3. National Center for the Medical Consequences of Spinal Cord Injury and Medical and Surgical Service, James J Peters VA Medical Center, Bronx, NY, USA

    Xin-hua Liu, Jiangping Pan & Christopher Cardozo

  4. Department of Medicine, Icahn School of Medicine, New York, NY, USA

    Xin-hua Liu, Jiangping Pan & Christopher Cardozo

  5. Endocrinology Service, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA

    Robert A. Adler

  6. Endocrine Division, Virginia Commonwealth University School of Medicine, Richmond, VA, USA

    Robert A. Adler

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  1. Ashraf S. Gorgey
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  2. Jacob A. Goldsmith
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  3. Refka E. Khalil
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  4. Xin-hua Liu
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  5. Jiangping Pan
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  6. Christopher Cardozo
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Contributions

ASG, JG, CC, RA designed research, provided data interpretation and manuscript writing; ASG and RK provided data collection, data handling and analysis; XL and JP conducting western blot and gene expression analyses; ASG provided study funding.

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Correspondence to Ashraf S. Gorgey.

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Communicated by William J. Kraemer.

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Gorgey, A.S., Goldsmith, J.A., Khalil, R.E. et al. Predictors of muscle hypertrophy responsiveness to electrically evoked resistance training after spinal cord injury. Eur J Appl Physiol 123, 479–493 (2023). https://doi.org/10.1007/s00421-022-05069-0

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