Richard A. PerryƗ1, Wesley S. HaynieƗ1, Katarina A. BejaranoƗ1, John T. KimƗ1, Kevin RobertsƗ1, Jeffrey C. Wolchok‡1, Nicholas P. Greene‡1, & Tyrone A. Washington‡1, 1University of Arkansas, Fayetteville, Arkansas

Skeletal muscle has a great ability to regenerate from damage. Still, regenerative capacity can be exceeded with extreme tissue loss, also known as volumetric muscle loss (VML). Causes of VML include munition explosions and excision of tumors (i.e. sarcomas). Patients suffering from VML do not fully recover force output in the affected limb. Adequate interventions have not been established to fully reverse this loss of function. Recent studies show that replacement tissue (i.e. autograph) into the VML defect site plus external growth stimuli (i.e. physical activity) show promise for optimizing force recovery in VML. PURPOSE: The purpose of this study is to evaluate the role of an autograph and physical activity on force output in a rat model of VML. METHODS: Fifteen Sprague-Dawley rats underwent VML. VML was caused by removing a defect equaling 20% of the tibialis anterior (TA) weight from the middle portion of the left TA. The defect was sutured back in to the defect site (autograph) shortly after removal. The right limb acted as a contralateral control. One week post-VML, the TAs were harvested from seven rats. The remaining eight rats were divided into cage or wheel activity groups. For two weeks post-VML, wheels were locked for both weeks (cage activity) or unlocked for the second week (wheel activity). Two weeks post-VML, TAs were harvested. All animals underwent electrophysiology immediately before harvest. Tissue was processed for histology to analyze cross-sectional area (CSA). Student’s t-test was conducted on all variables. RESULTS: At one week post-VML, force output in the left TA (1.1 N/kg ± .08 SE) was 48% of the right TA (2.3 N/kg ± .12 SE) (p<0.05). With the addition of activity during the second week post-VML, force output in the left TA (1.8 N/kg ± .17 SE) was 67% of the right TA (2.7 N/kg ± .09 SE) (p < 0.05). After two weeks of normal cage activity post-VML, force output in the left TA (1.1 N/kg ± .14 SE) was 41% of the right TA (2.7 N/kg ± .15 SE) (p < 0.05). One week post-VML, CSA (684 µm2 ± 42 SE) was 66% of CSA two weeks post-VML (1015 µm2 ± 147 SE) (p<0.05). CSA is similar between both groups two weeks post-VML. CONCLUSION: Wheel activity increases force output compared to cage activity following VML despite hypertrophy occurring in both groups. Therefore, hypertrophy is not the sole factor of increased force output two weeks post-VML.

This study was funded by NIH R15AR064481

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