Volumetric muscle loss disrupts length-dependent architectural and functional characteristics of skeletal muscle

Purpose/Aim Skeletal muscle architecture is a primary determinant of function. Volumetric muscle loss (VML) injury is destructive; however, the impact on muscle architecture is uncharacterized. Methods Architectural and functional effects of VML were assessed in rat tibialis anterior (TA) muscle model 4 weeks post-injury. Results VML caused a 31% and 33% reduction in muscle weight (p< 0.001) and fiber length (p= 0.002), respectively, culminating a 34% reduction of fiber to muscle length ratio (FL:ML;p< 0.001). Fiber pennation angle (+14%;p= 0.150) and physiological cross-sectional area (PCSA; -12%;p= 0.220) were unchanged. VML injury reduced peak isometric force (P-o) by 36% (p< 0.001), specific force (sP(o) = P-o/PCSA) by 41% (vs. P-o,p> 0.999), and force per gram muscle weight (P-o/mw) by 18% (vs. P-o,p< 0.001). VML injury increased the length at which P(o)was produced (L-o) by 8% (p= 0.009), and reduced functional excursion by 35% (p= 0.035). Conclusion The architectural changes after VML injury preserved PCSA, and therefore preserved "potential" maximal force-producing capacity. At most, only half the P(o)deficit was due directly to the cumulative effect of horizontal and longitudinal tissue loss. Highlighting the impact of longitudinal muscle loss, VML injury reduced fiber length, and FL:ML and grossly disrupted length-dependent functional properties. These findings raise the importance of augmenting length-dependent muscle properties to optimize functional recovery after VML injury.