Diaphragmatic glutathione levels and fatigue during loaded breathing: examination of the effect of n-acetylcysteine administration. Supinski, G. S., D. Stofan, R. Ciufo, A. Dimarco. Pulmonary Division, Department of Medicine, Case Western Reserve University and Metrohealth Medical Center, Cleveland, Ohio
APStracts 2:0163A, 1995.
Recent work has shown that loaded breathing produces alterations in diaphragmatic glutathione metabolism. Moreover, it has been suggested that alterations in glutathione levels may be related to the development of respiratory muscle fatigue and respiratory failure during loading. The purpose of this study was to determine if it was possible to augment diaphragmatic stores of reduced glutathione (GSH) and thereby delay the development of respiratory failure during loaded breathing by administering N-acetylcysteine (NAC), a glutathione precursor. We compared the effects of massive inspiratory loading on saline and NAC treated groups of decerebrate unanesthetized rats, with loading continued until respiratory arrest occurred. As controls, we also studied unloaded saline and NAC treated animals. After arrest, diaphragms were excised, measurement was made of diaphragm reduced (GSH) and oxidized (GSSG) glutathione concentrations, and assessment was made of in vitro diaphragm contractility (i.e. the force-frequency relationship and in vitro fatiguability). We found that loading of saline treated animals produced reductions in the diaphragm force-frequency curve, reductions in GSH, and increases in GSSG levels. NAC administration blunted loading induced decreases in diaphragm GSH levels and reduced the in vitro fatiguability of excised diaphragm muscle strips. NAC did not significantly alter the time to respiratory arrest, however, and also failed to alter the effect of loaded breathing on the diaphragm force-frequency relationship. These findings suggest that free radical mediated GSH depletion is not the limiting factor determining the development of respiratory failure in this model of loaded breathing. 

Received 14 February 1994; accepted in final form 24 February
1995.
APS Manuscript Number A161-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.