Hypoxemia enhances peripheral muscle oxidative stress in chronic obstructive pulmonary disease

Christelle Koechlin ^1*, Francois Maltais ², Didier Saey ², Annie Michaud ², Pierre Leblanc ³, Maurice Hayot ¹ and Christian Préfaut ¹

¹ UPRES EA 701 Laboratory of physiologie des interactions, France
² Centre de Recherche Hopital Laval Institut universitaire de Cardiologie et de Pneumologie, Canada
³ Centre de Recherche Hopital Laval Institut universitaire de Cardiologie et de Pneumologie, France

^* To whom correspondence should be addressed. E-mail: christelle_koechlin{at}hotmail.com.

Accepted 1 June 2005

Abstract

Background: Because oxidative stress affect muscle function, the underlying mechanism that might explain exercise-induced peripheral muscle oxidative stress in chronic obstructive pulmonary disease (COPD) patients is clinically relevant. This study investigated whether chronic hypoxemia in COPD worsens peripheral muscle oxidative stress and whether an abnormal muscle inflammatory process is associated.

Methods: Nine chronically hypoxemic and 9 non-hypoxemic patients performed repeated knee extensions until exhaustion. Vastus lateralis biopsies were performed before and 48 hours post-exercise. Muscle oxidative stress was evaluated by lipid peroxidation (lipofuscin and TBARs) and oxidized proteins. Inflammation was evaluated by quantifying muscle neutrophil and tumour necrosis factor- levels.

Results: When both groups were taken together, arterial oxygen pressure was positively correlated with quadriceps endurance time (n=18, r=0.57; p<0.05). At rest, quadriceps lipofuscin inclusions were significantly greater in hypoxemic compared to non-hypoxemic patients (2.9±0.2vs 2.0±0.3 inclusions/fibre; p<0.05). Exercise induced a greater increase in muscle TBARs and oxidized proteins in hypoxemic compared to non-hypoxemic patients (40.6±9.1 vs 10.1±5.8% and 51.2±11.9 vs 3.7±12.2%, respectively, both p=0.01). Neutrophil levels were significantly greater in hypoxemic compared to non-hypoxemic patients (53.1 ±11.6 vs 21.5±11.2 counts per fiber*10-3; p<0.05). Exercise did not alter muscle neutrophil levels in either group. Muscle TNF- was neither detected at baseline nor after exercise.

Conclusion: Chronic hypoxemia, was associated with lower quadriceps endurance time, and worsened muscle oxidative stress at rest and after exercise. Increased muscle neutrophil levels could be a source of the increased baseline oxidative damage. The involvement of a muscle inflammatory process in the exercise-induced oxidative stress of COPD patients remains to be demonstrated.

Keywords: exercise, inflammation, lipid peroxidation, lipofuscin, oxidized protein

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Duiverman, M L, Wempe, J B, Bladder, G, Jansen, D F, Kerstjens, H A M, Zijlstra, J G, Wijkstra, P J (2008). Nocturnal non-invasive ventilation in addition to rehabilitation in hypercapnic patients with COPD. Thorax 63: 1052-1057 [Abstract] [Full Text]  
• Lu, Z., Sack, M. N. (2008). ATF-1 Is a Hypoxia-responsive Transcriptional Activator of Skeletal Muscle Mitochondrial-uncoupling Protein 3. J. Biol. Chem. 283: 23410-23418 [Abstract] [Full Text]  
• Barreiro, E, Schols, A M W J, Polkey, M I, Galdiz, J B, Gosker, H R, Swallow, E B, Coronell, C, Gea, J, on behalf of the ENIGMA in COPD project, (2008). Cytokine profile in quadriceps muscles of patients with severe COPD. Thorax 63: 100-107 [Abstract] [Full Text]  
• Barreiro, E., Nowinski, A., Gea, J., Sliwinski, P. (2007). Oxidative stress in the external intercostal muscles of patients with obstructive sleep apnoea. Thorax 62: 1095-1101 [Abstract] [Full Text]  
• Ambrosino, N., Goldstein, R. (2007). Series on comprehensive management of end-stage COPD. Eur Respir J 30: 828-830 [Full Text]  
• Gosker, H. R, Zeegers, M. P, Wouters, E. F M, Schols, A. M W J (2007). Muscle fibre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis. Thorax 62: 944-949 [Abstract] [Full Text]  
• Vogiatzis, I., Stratakos, G., Simoes, D. C M, Terzis, G., Georgiadou, O., Roussos, C., Zakynthinos, S. (2007). Effects of rehabilitative exercise on peripheral muscle TNF{alpha}, IL-6, IGF-I and MyoD expression in patients with COPD. Thorax 62: 950-956 [Abstract] [Full Text]  
• Langen, R. C. J., Schols, A. M. W. J. (2007). Inflammation: friend or foe of muscle remodelling in COPD?. Eur Respir J 30: 605-607 [Full Text]  
• Tkac, J., Man, S. F. P., Sin, D. D. (2007). Review: Systemic consequences of COPD. Ther Adv Respir Dis 1: 47-59 [Abstract]  
• Clanton, T. L. (2007). Hypoxia-induced reactive oxygen species formation in skeletal muscle. J. Appl. Physiol. 102: 2379-2388 [Abstract] [Full Text]  
• Celli, B. R. (2006). Predicting mortality in chronic obstructive pulmonary disease: chasing the "holy grail".. Am. J. Respir. Crit. Care Med. 173: 1298-1299 [Full Text]  
• Fabbri, L. M., Luppi, F., Beghe, B., Rabe, K. F. (2006). Update in chronic obstructive pulmonary disease 2005.. Am. J. Respir. Crit. Care Med. 173: 1056-1065 [Full Text]  
• Fluck, M (2005). Hypoxaemia enhanced peripheral muscle oxidative stress in COPD. Thorax 60: 797-798 [Full Text]