Long-Term Skeletal Muscle Mitochondrial Dysfunction is Associated with Hypermetabolism in Severely Burned Children

Craig Porter, David Herndon, Elisabet Børsheim, Nisha Bhattarai, Tony Chao, Paul T. Reidy, Blake Rasmussen, Clark R. Andersen, Oscar Suman, Labros S. Sidossis

Research output: Contribution to journalArticle

15 Citations (Scopus)

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. Hypermetabolism was determined by the difference in predicted and measured metabolic rate. 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. 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 diphosphatase 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.

Original languageEnglish (US)
JournalJournal of Burn Care and Research
DOIs
StateAccepted/In press - Sep 7 2015

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Respiration
Skeletal Muscle
Energy Metabolism
Apyrase
Muscle Mitochondrion
Biopsy
Oligomycins
Respiratory Muscles
Thermogenesis
Saponins
Quadriceps Muscle
Wounds and Injuries
Burns
Analysis of Variance

ASJC Scopus subject areas

  • Emergency Medicine
  • Rehabilitation
  • Surgery

Cite this

Long-Term Skeletal Muscle Mitochondrial Dysfunction is Associated with Hypermetabolism in Severely Burned Children. / Porter, Craig; Herndon, David; Børsheim, Elisabet; Bhattarai, Nisha; Chao, Tony; Reidy, Paul T.; Rasmussen, Blake; Andersen, Clark R.; Suman, Oscar; Sidossis, Labros S.

In: Journal of Burn Care and Research, 07.09.2015.

Research output: Contribution to journalArticle

Porter, Craig ; Herndon, David ; Børsheim, Elisabet ; Bhattarai, Nisha ; Chao, Tony ; Reidy, Paul T. ; Rasmussen, Blake ; Andersen, Clark R. ; Suman, Oscar ; Sidossis, Labros S. / Long-Term Skeletal Muscle Mitochondrial Dysfunction is Associated with Hypermetabolism in Severely Burned Children. In: Journal of Burn Care and Research. 2015.
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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. Hypermetabolism was determined by the difference in predicted and measured metabolic rate. 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. 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 diphosphatase 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.",
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AU - Herndon, David

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AU - Chao, Tony

AU - Reidy, Paul T.

AU - Rasmussen, Blake

AU - Andersen, Clark R.

AU - Suman, Oscar

AU - Sidossis, Labros S.

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