Progression of Secondary Injury After Musculoskeletal Trauma—A Window of Opportunity?

Context:Acute musculoskeletal-injury management largely focuses on inhibiting secondary injury, although the data describing secondary injury and the timeline for its progression are sparse.Objective:To describe the timeline and early progression of secondary injury in skeletal muscle over the first 5 h after blunt trauma.Design:A controlled laboratory study with 2 independent variables (injury status and postinjury time point) in a 2 × 21 factorial.Setting:University research laboratory.Subjects:168 male Sprague Dawley rats (250 to 275 g).Interventions:Uniform blunt-contusion injury was caused to the right triceps surae using a drop-weight method; the contralateral limb served as an uninjured control. Both triceps surae were excised and flash frozen at 21 intervals across 5 h postinjury (8 animals, each 15 min).Main Outcome Measures:Cytochrome-c oxidase activity via reduction of triphenyltetrazolium chloride (TTC) to triphenyl-formazan.Results:There was an interaction effect (P = .041) between and main effects for both injury status (P < .0005) and postinjury time point (P = .038). In the first 30 min after injury, uninjured tissues did not differ from injured tissues, and both displayed TTC reduction rates in the vicinity of 7.1 ± 0.94 μg · mg−1 · h−1. Statistical differences between uninjured and injured tissues became evident starting at 30 min. TTC reduction for uninjured tissues did not change, but injured tissues declined in a roughly linear fashion across the entire 5-h period to 4.8 ± 1.04 μg · mg−1 · h−1.Conclusions:Cytochrome-c oxidase activity, an indicator of oxidative phosphorylation and mitochondrial viability, is diminished by events that follow muscle trauma. Loss of this enzymatic activity becomes statistically evident at 30 min postinjury and continues linearly for at least 5 h. This suggests that secondary injury is a slowly developing problem of more than 5 h duration. A window of opportunity for intervention may lie somewhere within the first 30 min after injury.