|
|
||||||||
Pulmonary Division, Department of Medicine, Case Western Reserve University, Cleveland 44106; and Metrohealth Medical Center, Cleveland, Ohio 44109
Received 26 September 1995; accepted in final form 15 November 1996.
Supinski, G. S., D. Stofan, R. Ciufo, and A. DiMarco.
N-acetylcysteine administration
alters 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 to
attenuate the development of diaphragm fatigue and/or delay the
onset of respiratory failure during loaded breathing by administering a
free radical scavenger. The purpose of the present experiment was,
therefore, to examine the effect of
N-acetylcysteine (NAC), a free radical
scavenger and glutathione precursor, on the evolution of respiratory
failure in decerebrate unanesthetized rats breathing against a large
inspiratory resistive load. We compared the inspiratory volume and
pressure generation over time in animals pretreated with either saline
or NAC (150 mg/kg) and then loaded until respiratory arrest. After
arrest, the diaphragm was excised, and samples were assayed for reduced
(GSH) and oxidized glutathione. As a control, we also assessed
respiratory function and glutathione concentrations in groups of
nonloaded saline- and NAC-treated animals. We found that NAC-treated
animals were able to tolerate loading better than the saline-treated
group, maintaining higher inspiratory pressures and sustaining higher
inspired volumes. Administration of NAC also increased the time that
animals could tolerate loading before the development of respiratory
arrest. In addition, although saline-treated loaded animals had
significant reductions in diaphragmatic GSH levels compared with
unloaded controls, the magnitude of this reduction was blunted by NAC
administration (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 the
values 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 of
development of respiratory failure during inspiratory resistive
loading.
free radicals; skeletal muscle
This article has been cited by other articles:
![]() |
L. F. Ferreira, L. A. A. Gilliam, and M. B. Reid L-2-Oxothiazolidine-4-carboxylate reverses glutathione oxidation and delays fatigue of skeletal muscle in vitro J Appl Physiol, July 1, 2009; 107(1): 211 - 216. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. K. Powers and M. J. Jackson Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production Physiol Rev, October 1, 2008; 88(4): 1243 - 1276. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. A. Goodyear-Bruch, J. Jegathesan, R. L. Clancy, and J. D. Pierce Apoptotic-Related Protein Expression in the Diaphragm and the Effect of Dopamine During Inspiratory Resistance Loading Biol Res Nurs, April 1, 2008; 9(4): 293 - 300. [Abstract] [PDF] |
||||
![]() |
L. F. Ferreira and M. B. Reid Muscle-derived ROS and thiol regulation in muscle fatigue J Appl Physiol, March 1, 2008; 104(3): 853 - 860. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Simpson and S. Iscoe Cardiorespiratory failure in rat induced by severe inspiratory resistive loading J Appl Physiol, April 1, 2007; 102(4): 1556 - 1564. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Vassilakopoulos and S. N. A. Hussain Ventilatory muscle activation and inflammation: cytokines, reactive oxygen species, and nitric oxide J Appl Physiol, April 1, 2007; 102(4): 1687 - 1695. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Pierce, C. Goodyear-Bruch, S. Hall, and R. L. Clancy Effect of dopamine on rat diaphragm apoptosis and muscle performance Exp Physiol, July 1, 2006; 91(4): 731 - 740. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. N. A. Hussain, G. Matar, E. Barreiro, M. Florian, M. Divangahi, and T. Vassilakopoulos Modifications of proteins by 4-hydroxy-2-nonenal in the ventilatory muscles of rats Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L996 - L1003. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Barreiro, J. B. Galdiz, M. Marinan, F. J. Alvarez, S. N. A. Hussain, J. Gea, and on behalf of the ENIGMA in COPD project Respiratory loading intensity and diaphragm oxidative stress: N-acetyl-cysteine effects J Appl Physiol, February 1, 2006; 100(2): 555 - 563. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Kristensen and T. Hansen Statistical analyses of repeated measures in physiological research: a tutorial Advan Physiol Educ, March 1, 2004; 28(1): 2 - 14. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Simpson, J. Van Eyk, and S. Iscoe Respiratory muscle injury, fatigue and serum skeletal troponin I in rat J. Physiol., February 1, 2004; 554(3): 891 - 903. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Pierce, R. L. Clancy, N. Smith-Blair, and R. Kraft Treatment and Prevention of Diaphragm Fatigue Using Low-Dose Dopamine Biol Res Nurs, January 1, 2002; 3(3): 140 - 149. [Abstract] [PDF] |
||||
![]() |
T.-X. JIANG, W. DARLENE REID, and J. D. ROAD Free Radical Scavengers and Diaphragm Injury Following Inspiratory Resistive Loading Am. J. Respir. Crit. Care Med., October 1, 2001; 164(7): 1288 - 1294. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M A Heunks and P N R. Dekhuijzen Respiratory muscle function and free radicals: from cell to COPD Thorax, August 1, 2000; 55(8): 704 - 716. [Full Text] |
||||
![]() |
D. Nethery, L. A. Callahan, D. Stofan, R. Mattera, A DiMarco, and G. Supinski PLA2 dependence of diaphragm mitochondrial formation of reactive oxygen species J Appl Physiol, July 1, 2000; 89(1): 72 - 80. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. STOFAN, L. A. CALLAHAN, A. F. DiMARCO, D. E. NETHERY, and G. S. SUPINSKI Modulation of Release of Reactive Oxygen Species by the Contracting Diaphragm Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): 891 - 898. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Supinski, D. Nethery, D. Stofan, and A. DiMarco Extracellular calcium modulates generation of reactive oxygen species by the contracting diaphragm J Appl Physiol, December 1, 1999; 87(6): 2177 - 2185. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. L. Clanton, L. Zuo, and P. Klawitter Oxidants and Skeletal Muscle Function: Physiologic and Pathophysiologic Implications Experimental Biology and Medicine, December 1, 1999; 222(3): 253 - 262. [Abstract] [Full Text] |
||||
![]() |
L. C. Lands, V. L. Grey, and A. A. Smountas Effect of supplementation with a cysteine donor on muscular performance J Appl Physiol, October 1, 1999; 87(4): 1381 - 1385. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Supinski, D. Nethery, D. Stofan, L. Szweda, and A. DiMarco Oxypurinol administration fails to prevent free radical-mediated lipid peroxidation during loaded breathing J Appl Physiol, September 1, 1999; 87(3): 1123 - 1131. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Nethery, D. Stofan, L. Callahan, A. DiMarco, and G. Supinski Formation of reactive oxygen species by the contracting diaphragm is PLA2 dependent J Appl Physiol, August 1, 1999; 87(2): 792 - 800. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |