title: Differential acute and chronic effects of burn trauma on murine skeletal muscle bioenergetics.
abstract: 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 3h, 24h, 4d and 10d 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 3h and 24h 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 3h and 24h 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 10d 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.
authors.affiliation: Metabolism Unit, Shriners Hospitals for Children, Galveston, TX, USA; Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: cr2porte@utmb.edu.
authors.forename: Craig
authors.initials: C
authors.lastname: Porter
authors.affiliation: Metabolism Unit, Shriners Hospitals for Children, Galveston, TX, USA; Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.affiliation: Metabolism Unit, Shriners Hospitals for Children, Galveston, TX, USA; Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Nisha
authors.initials: N
authors.lastname: Bhattarai
authors.affiliation: Metabolism Unit, Shriners Hospitals for Children, Galveston, TX, USA; Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: John O
authors.initials: JO
authors.lastname: Ogunbileje
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Szczesny
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabo
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Toliver-Kinsky
authors.affiliation: Metabolism Unit, Shriners Hospitals for Children, Galveston, TX, USA; Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Labros S
authors.initials: LS
authors.lastname: Sidossis
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D064131:Back Muscles / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002056:Burns / Q000378:metabolism*; D019069:Cell Respiration; D002908:Chronic Disease; D004734:Energy Metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D052097:Quadriceps Muscle / Q000378:metabolism / Q000473:pathology
keywords: Apoptosis; Burn; Hypermetabolism; Mitochondria; Skeletal muscle