The Effects of Physical Activity On Force Recovery From Volumetric Muscle Loss With Autograph Incorporation

Abstract

Skeletal muscle has an exceptional 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 following VML injury.PURPOSEThe purpose of this study is to evaluate the role of physical activity on force output in rats with autographs following VML injury.METHODSSixteen Sprague‐Dawley rats underwent VML. VML was caused by removing a defect equaling 20% of the left tibialis anterior (LTA) weight from the middle portion of the muscle. The defect was sutured back in to the defect site (autograph) shortly after removal. The right TA (RTA) acted as a contralateral control. For the week following VML surgery, wheels were locked for all rats to allow recovery from injury. At the end of that week (2 weeks post‐injury), wheels were unlocked for eight rats which were given ad libitum access whereas the wheel remained locked for the other eight rats and were allowed only normal cage activity. Within the wheel activity (WA) and cage activity (CA) groups, rats were divided into 2 week and 8 week groups (2WA, 2CA, 8WA, 8CA). At either two or eight weeks post‐VML, TAs were harvested. All animals underwent electrophysiology immediately before harvest. Tenotomy of the distal extensor digitalis longus and extensor halluces longus allowed for isolation of maximal isometric force of the TA. Tissue was processed for histology to analyze cross‐sectional area (CSA). Student's t‐test was conducted on all variables.RESULTSIn the 2WA group, force output in the LTA (1.8 N/kg ± .17 SE) was 67% of the RTA (2.7 N/kg ± .09 SE) (p < 0.05). In the 2CA group, force output in the LTA (1.1 N/kg ± .14 SE) was 41% of the RTA (2.7 N/kg ± .15 SE) (p < 0.05). In the 8WA group, force output of the LTA (2.1 N/kg ± .12 SE) was 69.5% of the RTA (3.0 N/kg ± .30 SE) (p < 0.05). In the 8CA, force output of the LTA (2.2 N/kg ± .13 SE) was 75.6% of the RTA (2.9 N/kg ± .04 SE) (p < 0.05). LTA CSA in the 2WA and 2CA was similar between both groups (1012 μm2 ± 54.1 and 1135 μm2 ± 204.1, respectively). Similarly, LTA CSA in the 8WA and 8CA was similar between both groups (1279 μm2 ± 17.8 and 1266 μm2 ± 58, respectively).CONCLUSIONIncorporation of physical activity increases force output at an earlier stage (2 weeks) than normal cage activity; however, continued physical activity does not promote additional force recovery at a later time point (8 weeks) as force output is similar between WA and CA groups.Support or Funding InformationThis study was funded by NIH R15AR064481This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.