Recent studies have suggested that
free radical scavenger administration reduces the rate of development of diaphragm
fatigue. Much of this work has been done, however, using in vitro muscle preparations; the purpose of the present study was to assess the effect of scavengers on in vivo diaphragm contractile function. To accomplish this, we compared the rate of development of
fatigue of the electrically stimulated diaphragm in four groups of dogs: (1) animals given intravenous
polyethylene glycol adsorbed
superoxide dismutase (
PEG-SOD, 2,000 units/kg) 1 h before a
fatigue trial; (2) a group given intravenous
dimethylsulfoxide (
DMSO, 0.5 ml/kg of a 50%
solution) before
fatigue; (3) a group given saline before
fatigue; and (4) a group treated with denatured
PEG-SOD (2,000 units/kg) before
fatigue. We measured diaphragmatic concentrations of
thiobarbituric acid reactive substances (TBAR), a marker of
free radical-mediated lipid peroxidation, on muscle samples taken at the conclusion of
fatigue trials. As a control, we also measured TBAR concentrations for muscle samples taken from nonfatigued diaphragm. We found that the rate of development of diaphragm
fatigue was much greater in saline and denatured
PEG-SOD-treated groups than for animals pretreated with either
PEG-SOD or
DMSO, with force falling to 23 +/- 4, 21 +/- 4, 50 +/- 7, and 47 +/- 6% of its initial value, respectively, over a 2-h period of electrophrenic stimulation in these four groups of animals (p < 0.01). TBAR concentrations in fatigued diaphragm from saline and denatured
PEG-SOD-treated animals were significantly higher than levels for either nonfatigued fresh diaphragm or fatigued diaphragm taken from
PEG-SOD- or
DMSO-treated animals (p < 0.01). These data suggest that diaphragm
fatigue resulting from repetitive low-frequency stimulation is associated with lipid peroxidation within this muscle and that pretreatment with
free radical scavengers prevents lipid peroxidation and reduces the rate of development of
fatigue.