Neutrophil superoxide anion-generating capacity, endothelial function and oxidative stress in chronic heart failure: Effects of short- and long-term vitamin C therapy
Gr. Ellis et al., Neutrophil superoxide anion-generating capacity, endothelial function and oxidative stress in chronic heart failure: Effects of short- and long-term vitamin C therapy, J AM COL C, 36(5), 2000, pp. 1474-1482
Citations number
42
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
OBJECTIVES First, we sought to study the effects of short- and long-term vi
tamin C therapy on oxidative stress and endothelial dysfunction in chronic
heart failure (CHF), and second, we sought to investigate the role of neutr
ophils as a cause of oxidative stress in CHF.
BACKGROUND Oxidative stress may contribute to endothelial dysfunction in CH
F. Vitamin C ameliorates endothelial dysfunction in CHF, presumably by redu
cing oxidative stress, but this is unproven.
METHODS We studied 55 patients with CHF (ischemic and nonischemic etiologie
s) and 15 control subjects. Flow-mediated dilation (FMD) in the brachial ar
tery was measured by ultrasound wall-tracking, neutrophil superoxide anion
(O-2(-)) generation by lucigenin-enhanced chemiluminescence and oxidative s
tress by measurement of free radicals (FRs) in venous blood using electron
paramagnetic resonance (EPR) spectroscopy and plasma thiobarbituric acid re
active substances (TEARS). Measurements were performed at baseline in all s
ubjects. The effects of short-term (intravenous) and long-term (oral) vitam
in C therapy versus placebo were tested in patients with nonischemic CHF.
RESULTS At baseline, FRs were higher in patients with CHF than in control s
ubjects (p < 0.01), TEARS were greater (p < 0.005), neutrophil O-2(-)-gener
ating capacity was enhanced (p < 0.005) and FMD was lower (p < 0.0001). Com
pared with placebo, short-term vitamin C therapy reduced FR levels (p < 0.0
5), 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). Endoth
elial 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 stre
ss, increases FMD and, when given long term, decreases neutrophil O-2(-) ge
neration, but the lack of a correlation between changes in endothelial func
tion and oxidative stress with vitamin C implies possible additional non-an
tioxidant benefits of vitamin C. (C) 2000 by the American College of Cardio
logy.