Hypoxaemia enhances peripheral muscle oxidative stress in chronic obstructive pulmonary disease

Abstract

Background: Because oxidative stress affects muscle function, the underlying mechanism to explain exercise induced peripheral muscle oxidative stress in patients with chronic obstructive pulmonary disease (COPD) is clinically relevant. This study investigated whether chronic hypoxaemia in COPD worsens peripheral muscle oxidative stress and whether an abnormal muscle inflammatory process is associated with it. Methods: Nine chronically hypoxaemic and nine non-hypoxaemic patients performed repeated knee extensions until exhaustion. Biopsy specimens were taken from the vastus lateralis muscle before and 48 hours after exercise. Muscle oxidative stress was evaluated by lipid peroxidation (lipofuscin and thiobarbituric acid reactive substances (TBARs)) and oxidised proteins. Inflammation was evaluated by quantifying muscle neutrophil and tumour necrosis factor (TNF)-a 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 hypoxaemic patients than in non-hypoxaemic patients (2.9 (0.2) v 2.0 (0.3) inclusions/fibre; p,0.05). Exercise induced a greater increase in muscle TBARs and oxidised proteins in hypoxaemic patients than in non-hypoxaemic patients (40.6 (9.1)% v 10.1 (5.8)% and 51.2 (11.9)% v 3.7 (12.2)%, respectively, both p = 0.01). Neutrophil levels were significantly higher in hypoxaemic patients than in non-hypoxaemic patients (53.1 (11.6) v 21.5 (11.2) counts per fibre 6 10 23 ; p,0.05). Exercise did not alter muscle neutrophil levels in either group. Muscle TNF-a was not detected at baseline or after exercise. Conclusion: Chronic hypoxaemia 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 patients with COPD remains to be shown.

Skeletal Muscle Dysfunction in Patients with Chronic Obstructive Pulmonary Disease

“…Jakobsson and colleagues (1990) have reported that adenosine triphosphate (ATP), glycogen and creatine phosphate levels in quadriceps muscle fi bers are signifi cantly reduced in COPD patients with chronic respiratory failure as compared to those without respiratory failure and they described a significant correlation between muscle metabolites and arterial PO 2 . Moreover, chronic hypoxemic COPD patients show greater levels of exercise-induced lipid peroxidation and oxidized proteins in their quadriceps muscles than do nonhypoxemic COPD patients (Koechlin et al 2005). As with the case of lower limb muscles, maximum diaphragm force and diaphragm endurance are both signifi cantly reduced in COPD patients with chronic hypoxemia, although inhalation of O 2 for 15min elicits an increase in diaphragm strength and endurance (Zattara-Hartmann et al 1995).…”

Inactivity and Inflammation in the Critically Ill Patient

“…Activity or mobility in critically ill patients may initiate hypoxia; hypoxia is a source of increased oxidants [94,95]. Koechlin and colleagues [96] suggest that arterial oxygenation is key to reducing oxidative stress in patients who have COPD. In a sample of 10 subjects who had COPD, plasma levels of products of oxidative stress were increased significantly over similar products formed by seven controls at 6 hours after one episode of quadriceps endurance activity.…”

Efeitos sistêmicos da hipoxemia noturna em pacientes com doença pulmonar obstrutiva crônica sem síndrome da apnéia obstrutiva do sono

“…(4) However, the systemic effects of nocturnal hypoxemia have been little studied in patients with COPD.…”