title: Long-Term Skeletal Muscle Mitochondrial Dysfunction is Associated with Hypermetabolism in Severely Burned Children.
abstract: The long-term impact of burn trauma on skeletal muscle bioenergetics remains unknown. Here, the authors determined respiratory capacity and function of skeletal muscle mitochondria in healthy individuals and in burn victims for up to 2 years postinjury. Biopsies were collected from the m. vastus lateralis of 16 healthy men (26 ± 4 years) and 69 children (8 ± 5 years) with burns encompassing ≥30% of their total BSA. Seventy-nine biopsies were collected from cohorts of burn victims at 2 weeks (n = 18), 6 months (n = 18), 12 months (n = 25), and 24 months (n = 18) postburn. Hypermetabolism was determined by the difference in predicted and measured metabolic rate. Mitochondrial respiration was determined in saponin-permeabilized myofiber bundles. Outcomes were modeled by analysis of variance, with differences in groups assessed by Tukey-adjusted contrasts. Burn patients were hypermetabolic for up to 2 years postinjury. Coupled mitochondrial respiration was lower at 2 weeks (17 [8] pmol/sec/mg; P < .001), 6 months (41 [30] pmol/sec/mg; P = .03), and 12 months (35 [14] pmol/sec/mg; P < .001) postburn compared with healthy controls (58 [13] pmol/sec/mg). Coupled respiration was greater at 6, 12, and 24 months postburn vs 2 weeks postburn (P < .001). Mitochondrial adenosine diphosphate and oligomycin sensitivity (measures of coupling control) were lower at all time-points postburn vs control (P < .05), but greater at 6, 12, and 24 months postburn vs 2 weeks postburn (P < .05). Muscle mitochondrial respiratory capacity remains significantly lower in burn victims for 1-year postinjury. Mitochondrial coupling control is diminished for up to 2 years postinjury in burn victims, resulting in greater mitochondrial thermogenesis. These quantitative and qualitative derangements in skeletal muscle bioenergetics likely contribute to the long-term pathophysiological stress response to burn trauma.
authors.affiliation: From the *Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas; †Department of Surgery, University of Texas Medical Branch, Galveston; ‡University of Arkansas for Medical Science, Arkansas Children's Nutrition Center, and Arkansas Children's Hospital Research Institute, Little Rock; §Department of Rehabilitation Sciences, ‖Department of Nutrition and Metabolism, ¶Institute of Translational Sciences, and #Department of Internal Medicine, University of Texas Medical Branch, Galveston.
authors.forename: Craig
authors.initials: C
authors.lastname: Porter
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Elisabet
authors.initials: E
authors.lastname: Børsheim
authors.forename: Nisha
authors.initials: N
authors.lastname: Bhattarai
authors.forename: Tony
authors.initials: T
authors.lastname: Chao
authors.forename: Paul T
authors.initials: PT
authors.lastname: Reidy
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
authors.forename: Clark R
authors.initials: CR
authors.lastname: Andersen
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Suman
authors.forename: Labros S
authors.initials: LS
authors.lastname: Sidossis
mesh_terms: D000293:Adolescent; D000328:Adult; D002056:Burns / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology*; D013997:Time Factors; D055815:Young Adult