Oxidative stress and COPD: the effect of oral antioxidants on skeletal muscle fatigue

Abstract

Purpose: Oxidative stress may contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). This study sought to determine the effect of an acute oral antioxidant cocktail (AOC, vitamins C and E, and alpha-lipoic acid) on skeletal muscle function during dynamic quadriceps exercise in COPD.

Methods: Ten patients with COPD performed knee extensor exercise to exhaustion and isotime trials after either the AOC or placebo (PL). Pre- to postexercise changes in quadriceps maximal voluntary contractions and potentiated twitch forces (Q(tw,pot)) quantified quadriceps fatigue.

Results: Under PL conditions, the plasma electron paramagnetic resonance (EPR) spectroscopy signal was inversely correlated with the forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC), an index of lung dysfunction (r = -0.61, P = 0.02), and maximal voluntary contraction force (r = -0.56, P = 0.04). AOC consumption increased plasma ascorbate levels (10.1 ± 2.2 to 24.1 ± 3.8 μg · mL(-1), P < 0.05) and attenuated the area under the curve of the EPR spectroscopy free radical signal (11.6 ± 3.7 to 4.8 ± 2.2 AU, P < 0.05), but it did not alter the endurance time or quadriceps fatigue. The ability of the AOC to decrease the EPR spectroscopy signal, however, was prominent in those with high basal free radicals (n = 5, PL, 19.7 ± 5.8, to AOC, 5.8 ± 4.5 AU; P < 0.05) with minimal effects in those with low levels (n = 5, PL, 1.6 ± 0.5, to AOC, 3.4 ± 1.1 AU).

Discussion: These data document a relation between directly measured free radicals and lung dysfunction and the ability of the AOC to decrease oxidative stress in COPD. Acute amelioration of free radicals, however, does not appear to affect dynamic quadriceps exercise performance.

Figures

Figure 1. Relationships between the forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) and maximal voluntary quadriceps contraction (MVC) with resting free radical concentration assessed by electron paramagnetic resonance (EPR) spectroscopy

Resting free radical concentration (AUC, arbitrary units) was moderately inversely correlated with A: FEV1/FVC and B: baseline quadriceps MVC. *p < 0.05, one-tailed test.

Figure 2. Resting antioxidant and oxidant status assayed in the plasma following placebo (PL) and antioxidant cocktail (AOC) consumption

Data are presented as mean ± S.E.M. AOC consumption resulted in a 140% increase in plasma ascorbate (A) and a 63% reduction in the free radical concentration assessed by electron paramagnetic resonance (EPR) spectroscopy (presented with representative spectroscopy signal) and expressed as the area under the curve (AUC, arbitrary units) (B). *Significantly different from placebo condition, p

Figure 3. Endurance time to exhaustion and end-exercise quadriceps fatigue assessed following constant-load knee extensor exercise to exhaustion (performance trials) and following exercise matched for intensity (23±3 W) and duration (isotime trials) with either the consumption of a placebo (PL) or an antioxidant cocktail (AOC)

Data are presented as mean ± S.E.M. Quadriceps fatigue values represent the percent change from pre- to postexercise. Qtw,pot, potentiated twitch force; MVC, maximal voluntary contraction. There were no significant differences.

Figure 4. Physiological responses to constant workload isotime knee extensor exercise matched for intensity (23±3 W) and duration (7.1±0.7 min) following consumption of either a placebo (PL) or an antioxidant cocktail (AOC)

Group mean data (± S.E.M) over the first four minutes of exercise, which were attained by all subjects. The final time point represents end-exercise values. End exercise values for femoral blood flow are not reported due to loss of signal. VE, ventilation; VO2, oxygen consumption; VCO2, carbon dioxide production; iEMG, integrated electromyogram from the vastus lateralis. There were no significant differences between interventions.

Figure 5. Individual chang es in the α-Phenyl-tert-butylnitrone (PBN) spin adduct area under the curve (AUC) assessed by electron paramagnetic resonance (EPR) spectroscopy following the ingestion of both the placebo (PL) and antioxidant cocktail (AOC)

Individual responses have been separated into two groups, those with low (left) and high (right) basal free radical levels in the PL condition. As illustrated, the AOC appeared to only have an effect in those with high basal free radical levels, evidence that the baseline free radical load influences the efficacy of the AOC. *Significantly different from placebo condition, p