Ascorbate infusion increases skeletal muscle fatigue resistance in patients with chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is associated with systemic oxidative stress and skeletal muscle dysfunction. The purpose of this study was to examine the impact of intravenous ascorbate administration (AO) on biological markers of antioxidant capacity and oxidative stress, and subsequently skeletal muscle function during dynamic, small muscle mass exercise in patients with COPD. Ten patients with spirometric evidence of COPD performed single-leg knee extensor (KE) trials matched for intensity and time (isotime) following intravenous ascorbate (2 g) or saline infusion (PL). Quadriceps fatigue was quantified by changes in force elicited by maximal voluntary contraction (MVC) and magnetic femoral nerve stimulation (Qtw,pot). AO administration significantly increased antioxidant capacity, as measured by the ferric-reducing ability of plasma (PL: 1 ± 0.1 vs. AO: 5 ± 0.2 mM), and significantly reduced malondialdehyde levels (PL: 1.16 ± 0.1 vs. AO: 0.97 ± 0.1 mmol). Additionally, resting blood pressure was significantly reduced (PL: 104 ± 4 vs. AO: 93 ± 6 mmHg) and resting femoral vascular conductance was significantly elevated after AO (PL: 2.4 ± 0.2 vs. AO: 3.6 ± 0.4 ml·min(-1)·mmHg(-1)). During isotime exercise, the AO significantly attenuated both the ventilatory and metabolic responses, and patients accumulated significantly less peripheral quadriceps fatigue, as illustrated by less of a fall in MVC (PL: -11 ± 2% vs. AO: -5 ± 1%) and Qtw,pot (PL: -37 ± 1% vs. AO: -30 ± 2%). These data demonstrate a beneficial role of AO administration on skeletal muscle fatigue in patients with COPD and further implicate systemic oxidative stress as a causative factor in the skeletal muscle dysfunction observed in this population.

Keywords: ascorbate; free radicals; peripheral fatigue.

Fig. 1.

Study protocol schematic. MVC, maximal voluntary contraction. Q_tw,pot, potentiated twitch force.

Fig. 2.

Quantitative assessment of antioxidants and markers of oxidative stress after intravenous saline (PL) or ascorbate (AO) administration. FRAP, ferric-reducing ability of plasma. Values are presented as means ± SE. *Significantly different from the PL condition.

Fig. 3.

Resting mean arterial pressure and hemodynamic parameters following intravenous PL or AO administration. Values are presented as means ± SE. *Significantly different from the PL condition.

Fig. 4.

Physiological responses to constant workload isotime knee extensor exercise matched for intensity and duration following intravenous PL or AO administration. Group mean data (±SE) over the first 4 min of exercise, which were attained by all subjects. The final time point represents end-exercise values, which were not obtained for femoral blood flow due to loss of signal. VE/Vco₂, ventilation relative to carbon dioxide production; Vco₂, carbon dioxide production; Vo₂, oxygen consumption; iEMG, integrated electromyogram from the vastus lateralis. *Significantly different from the PL condition. #P = 0.09.

Fig. 5.

Changes from preexercise values in quadriceps muscle function following constant-load knee extensor exercise matched for intensity and duration preceded by either intravenous PL or AO administration. Data are presented as means ± SE. *Significantly different from the PL condition.