Oxidative stress and peripheral skeletal muscle dysfunction in rats with emphysema.

BACKGROUND

Peripheral skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD) may be due to the disease per se or as a result of concomitant confounding factors. Although the mechanistic basis for this functional impairment is uncertain, oxidative stress may play a role. The purpose of this study was to investigate whether local oxidative stress is associated with the reduced peripheral skeletal muscle performance in rats with emphysema.

METHODS

In situ mechanical properties of gastrocnemius were measured in Sprague-Dawley rats 5 months after intratracheal instillation of either elastase (EMP, n = 10) or normal saline (CON, n = 10). Lipofuscin inclusions, myocyte apoptosis and antioxidant enzyme activities were examined in the gastrocnemius muscle.

RESULTS

Lipofuscin inclusions were significantly higher in the gastrocnemius muscle of EMP compared with CON (3.2 + or - 0.4 vs. 1.7 + or - 0.4, P < 0.01). The activities of antioxidant enzymes were significantly increased in muscle homogenates of EMP as compared to CON. No significant differences were found in myocyte apoptosis between EMP and CON (1.2 + or - 0.9 vs. 1.0 + or - 0.8, P > 0.05). EMP decreased the fatigue endurance of gastrocnemius muscle (half-time to fatigue recovery: (150.0 + or - 55.4) seconds vs. (55.2 + or - 29.3) seconds, P < 0.01) and had no effect on maximal tetanic force ((467.4 + or - 36.6) g vs. (493.2 + or - 30.5) g, P > 0.05). A significantly positive correlation was found between the level of lipofuscin inclusions and the half-time to fatigue recovery of gastrocnemius muscle in EMP (r = 0.664, P < 0.05).

CONCLUSION

Local oxidative stress may have important functional consequences for peripheral skeletal muscle in rats with EMP.