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Effects of Darbepoetin Alfa on Plasma Mediators of Oxidative and Nitrosative Stress in Anemic Patients With Chronic Heart Failure Secondary
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| 03.05.2009, 14:50 |
Increased oxidative and nitrosative stress are important mediators of left ventricular (LV)
and vascular dysfunction in patients with chronic heart failure (CHF). This study investigated
the effects of darbepoetin alfa on plasma markers of oxidative and nitrosative stress
in patients with CHF with anemia. Thirty patients with CHF (LV ejection fraction [LVEF]
<40%, hemoglobin <12.5 g/dl, and serum creatinine <2.5 mg/dl) were randomly assigned
(1:1) to receive either a 3-month darbepoetin alfa regimen at 1.5 g/kg every 20 days plus
oral iron or placebo plus oral iron. Plasma B-type natriuretic peptide (BNP), markers of
oxidative (oxidative, malondialdehyde, carbonyl proteins; antioxidative, glutathione) and
nitrosative (nitrotyrosine) stress, LVEF, and 6-minute walked distance were assessed at
baseline and after treatment. A significant improvement in LVEF and 6-minute walked
distance was observed in only darbepoetin-treated patients. Plasma BNP (F 14.8, p
001), malondialdehyde (F 9.4, p 0.006), protein carbonyl (F 9.2, p 0.006), and
nitrotyrosine (F 4.4, p 0.045) were significantly decreased, along with an increase in
antioxidative glutathione (F 4.2, p 0.049) after darbepoetin alfa treatment. These
factors were unaffected in placebo-treated patients. Darbepoetin-induced percentages of
change in carbonyl protein significantly correlated with respective changes in plasma BNP
(r 0.55, p <0.05) and LVEF (r 0.46, p <0.05). Finally, a drug-induced percentage
of decrease in nitrotyrosine significantly correlated with the respective improvement in
6-minute walked distance (r0.63, p <0.05). In conclusion, darbepoetin alfa attenuated
deleterious effects of oxidative and nitrosative stress into the cardiovascular system of
anemic patients with CHF, improving also cardiac function and exercise capacity. © 2009
Elsevier Inc. (Am J Cardiol 2009;103:1134 –1138)
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| Категория: Статьи | Добавил: nbylova
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