| Abstract: | Supinski, G. S., D. Stofan, R. Ciufo, and A. DiMarco.N-acetylcysteine administrationalters the response to inspiratory loading in oxygen-supplemented rats.J. Appl. Physiol. 82(4): 1119-1125, 1997. Based on recent studies, it has been suggested that free radicals are elaborated in the respiratory muscles during strenuous contractions and contribute to the development of muscle fatigue. If this theory is correct, then it should be possible toattenuate the development of diaphragm fatigue and/or delay theonset of respiratory failure during loaded breathing by administering afree radical scavenger. The purpose of the present experiment was,therefore, to examine the effect ofN-acetylcysteine (NAC), a free radicalscavenger and glutathione precursor, on the evolution of respiratoryfailure in decerebrate unanesthetized rats breathing against a largeinspiratory resistive load. We compared the inspiratory volume andpressure generation over time in animals pretreated with either salineor NAC (150 mg/kg) and then loaded until respiratory arrest. Afterarrest, the diaphragm was excised, and samples were assayed for reduced(GSH) and oxidized glutathione. As a control, we also assessedrespiratory function and glutathione concentrations in groups ofnonloaded saline- and NAC-treated animals. We found that NAC-treatedanimals were able to tolerate loading better than the saline-treatedgroup, maintaining higher inspiratory pressures and sustaining higherinspired volumes. Administration of NAC also increased the time thatanimals could tolerate loading before the development of respiratoryarrest. In addition, although saline-treated loaded animals hadsignificant reductions in diaphragmatic GSH levels compared withunloaded controls, the magnitude of this reduction was blunted by NACadministration (i.e., GSH averaged 965 ± 113, 568 ± 83, 907 ± 39, and 784 ± 61 nmol/g for unloaded-saline, loaded-saline,unloaded-NAC, and loaded-NAC groups, P < 0.05, with the value for the loaded-saline group lower than thevalues for the two unloaded groups; GSH for the loaded-NAC group was not different, however, from unloaded controls). These data demonstrate that administration of NAC, a free radical scavenger, slows the rate ofdevelopment of respiratory failure during inspiratory resistiveloading. |
