Diaphragmatic superoxide release is affected by muscle length and carbon dioxide levels

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

Research output: Contribution to journalArticlepeer-review


Recent reports have demonstrated that free radicals contribute to the development of diaphragmatic fatigue. Studies have also demonstrated that the diaphragm fatigue rate is altered by changing muscle length or carbon dioxide levels (CO2). The purpose of this study was to determine if diaphragmatic Superoxide release during contraction is altered by increasing CO2 or reducing muscle length. Studies employed an isolated, arterially perfused rat diaphragm preparation (n = 25) in which Superoxide release was assessed by measuring arterio-venous cytochrome c reduction gradients across this muscle and calculating cytochrome c reduction rates (CCRR). Diaphragm force was measured using a Grass FT10 transducer. We examined CCRR during isometric electrically induced contractions (15 stimulus trains/min) in four groups: (a) controls stimulated at 20 Hz with length set to Lo and with a CO2 level of 5%, (b) a group in which CO2 was increased to 15%, (c) a group with length reduced to 65%Lo, and (d) an Lo group in which stimulation frequency was reduced so as to generate forces similar to the 65% Lo group. We found that CCRR was significantly higher (P< .05) in controls (280 ±37) than for the other groups, with CCRR of 148 ± 28 for 15% CO2, 149 ±49 for 65% Lo and 125 ± 29 pmol/min for the low frequency stimulation group. The lower Superoxide release of shortened muscles appeared to be due to lower force development, since Superoxide release in Lo muscles decreased to a similar degree when stimulation frequency was reduced so as to match the force developed by shortened muscles. Forces developed by high CO2 muscles were similar to controls, however, indicating that the effect of high CO2 to reduce Superoxide production may represent a direct effect of CO2 on free radical metabolism.

Original languageEnglish
Pages (from-to)A741
JournalFASEB Journal
Issue number3
StatePublished - 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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