Oxidative pathophysiology following volumetric muscle loss injury in a porcine model.

Volumetric muscle loss (VML) occurs after severe orthopedic trauma and results in loss of muscle fibers and function that can leave patients permanently disabled. Although animals models of VML are useful to test possible therapeutic strategies, the pathophysiological characteristics of remaining skeletal muscle and changes in metabolism are not thoroughly understood. Herein, alterations of neuromuscular function, muscle fiber morphology, myosin heavy chain expression, and myofiber mitochondrial respiration were evaluated in an adult Yorkshire swine VML injury model. VML injured animals showed reduced peak isometric strength ( < 0.05) and a shift toward smaller muscle fibers independent of fiber type ( < 0.001). The muscle remaining after VML had a greater distribution of type I fibers and lower distribution of type II fibers ( < 0.001). Skeletal muscle mitochondrial state 2 and state 3, reflecting complex I respiration, increased after injury ( < 0.05) with a consistent trend to display higher oxygen flux per milligram of tissue. However, this was largely driven by increased mitochondrial content after VML which was associated with higher mitochondrial fission (FIS-1 protein levels). This study demonstrates an underlying perturbation of oxidative metabolism within the remaining musculature following surgical creation of an isolated, sterile VML injury in a porcine model that may be influential to the development of insidious pathophysiology and regenerative and rehabilitative therapies. The natural injury sequela of volumetric muscle loss (VML) and associated pathophysiology of the remaining muscle is still incompletely understood. Herein we demonstrate a chronic muscle function deficit, with an increase in type I muscle fibers and parallel increase in oxidative capacity of remaining skeletal muscle. It is possible that the alteration in oxidative capacity after VML could largely be due to heightened mitochondrial activity and an increase in mitochondrial abundance.