Sepsis increases contraction-related superoxide generation in the diaphragm

D. Nethery, A. DiMarco, D. Stofan, G. Supinski

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2 Scopus citations


Recent work indicates that tree radicals mediate sepsis-induced diaphragmatic dysfunction, hut these previous experiments did not establish the source of the responsible free radical species. This phenomenon could, however, be explained if sepsis elicits a cytokine-mediated upregulation of contraction-related superoxide generation. The purpose of the present study was to test this hypothesis by examining the effect of sepsis on rat diaphragm superoxide generation. Rats were sacrificed 18 hr after injection with either saline (n = 6) or endotoxin (8 mg/kg, n = 6). In vitro hemdiaphragms were then prepared and intracellular superoxide generation during electrically induced contractions (0.5 sec duration 20 Hz trains delivered for 10 min) was assessed by measuring the conversion of hydroethidine to ethidium. Superoxide generation was negligible in noncontracting diaphragms from both groups (0.03 ±SE 0.01 O.D. units) but was marked in stimulated control diaphragms (0.16 ±0.02 O.D.) and even more pronounced (0.24 ±0.02 O.D.) for diaphragms from septic animals (p<.05). This enhanced superoxide generation occurred despite the fact that the force-time integral for control diaphragms was higher than for the septic group (p<.02). In additional studies we found that superoxide generation (both septic and controls) was not altered by administering apocynin, an inhibitor of neurophil superoxide production, or by endothelial stripping. These data indicate that superoxide generation per unit force is markedly enhanced in diaphragm from endotoxin-treated animals. We speculate that superoxide generated in this fashion plays an important role in producing sepsis-related skeletal muscle dysfunction.

Original languageEnglish
Pages (from-to)A13
JournalFASEB Journal
Issue number3
StatePublished - 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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