Neutrophil superoxide anion-generating capacity, endothelial function and oxidative stress in chronic heart failure: Effects of short- and long-term vitamin C therapy

OBJECTIVES First, we sought to study the effects of short- and long-term vitamin C therapy on oxidative stress and endothelial dysfunction in chronic heart failure (CHF), and second, we sought to investigate the role of neutrophils as a cause of oxidative stress in CHF. BACKGROUND Oxidative stress may contribute to endothelial dysfunction in CHF. Vitamin C ameliorates endothelial dysfunction in CHF, presumably by reducing oxidative stress, but this is unproven. METHODS We studied 55 patients with CHF (ischemic and nonischemic etiologies) and 15 control subjects. Flow-mediated dilation (FMD) in the brachial artery was measured by ultrasound wall-tracking, neutrophil superoxide anion (O-2(-)) generation by lucigenin-enhanced chemiluminescence and oxidative stress by measurement of free radicals (FRs) in venous blood using electron paramagnetic resonance (EPR) spectroscopy and plasma thiobarbituric acid reactive substances (TEARS). Measurements were performed at baseline in all subjects. The effects of short-term (intravenous) and long-term (oral) vitamin C therapy versus placebo were tested in patients with nonischemic CHF. RESULTS At baseline, FRs were higher in patients with CHF than in control subjects (p < 0.01), TEARS were greater (p < 0.005), neutrophil O-2(-)-generating capacity was enhanced (p < 0.005) and FMD was lower (p < 0.0001). Compared with placebo, short-term vitamin C therapy reduced FR levels (p < 0.05), tended to reduce TEARS and increased FMD (p < 0.05), but did not affect neutrophil O-2(-)-generating capacity. Long-term vitamin C therapy reduced FR levels (p < 0.05), reduced TEARS (p < 0.05) and improved FMD (p < 0.05), but also reduced neutrophil O-2(-)-generating capacity (p < 0.05). Endothelial dysfunction was not related to oxidative stress, and improvements in FMD with vitamin C therapy did not relate to reductions in oxidative stress. CONCLUSIONS Oxidative stress is increased in ischemic and nonischemic CHF, and neutrophils may be an important cause. Vitamin C reduces oxidative stress, increases FMD and, when given long term, decreases neutrophil O-2(-) generation, but the lack of a correlation between changes in endothelial function and oxidative stress with vitamin C implies possible additional non-antioxidant benefits of vitamin C. (C) 2000 by the American College of Cardiology.