Differential acute and chronic effects of burn trauma on murine skeletal muscle bioenergetics

Altered skeletal muscle mitochondrial function contributes to the pathophysiological stress response to burns. However, the acute and chronic impact of burn trauma on skeletal muscle bioenergetics remains poorly understood. Here, we determined the temporal relationship between burn trauma and mitochondrial function in murine skeletal muscle local to and distal from burn wounds. Male BALB/c mice (8-10 weeks old) were burned by submersion of the dorsum in water (∼95 °C) to create a full thickness burn on ∼30% of the body. Skeletal muscle was harvested spinotrapezius underneath burn wounds (local) and the quadriceps (distal) of sham and burn treated mice at 3 h, 24 h, 4 d and 10 d post-injury. Mitochondrial respiration was determined in permeabilized myofiber bundles by high-resolution respirometry. Caspase 9 and caspase 3 protein concentration were determined by western blot. In muscle local to burn wounds, respiration coupled to ATP production was significantly diminished at 3 h and 24 h post-injury (P < 0.001), as was mitochondrial coupling control (P < 0.001). There was a 5- (P < 0.05) and 8-fold (P < 0.001) increase in respiration in response to cytochrome at 3 h and 24 h post burn, respectively, indicating damage to the outer mitochondrial membranes. Moreover, we also observed greater active caspase 9 and caspase 3 in muscle local to burn wounds, indicating the induction of apoptosis. Distal muscle mitochondrial function was unaltered by burn trauma until 10 d post burn, where both respiratory capacity (P < 0.05) and coupling control (P < 0.05) were significantly lower than sham. These data highlight a differential response in muscle mitochondrial function to burn trauma, where the timing, degree and mode of dysfunction are dependent on whether the muscle is local or distal to the burn wound.