Parissis John T, Kourea Kallirrhoe, Andreadou Ioanna, Ikonomidis Ignatios, Markantonis Sophia, Ioannidis Konstadinos, Paraskevaidis Ioannis, Iliodromitis Efstathios, Filippatos Gerasimos, Kremastinos Dimitrios Th
Heart Failure Clinic, Attikon University Hospital, University of Athens, Greece.
Am J Cardiol. 2009 Apr 15;103(8):1134-8. doi: 10.1016/j.amjcard.2008.12.041. Epub 2009 Feb 28.
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 microg/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 (r = -0.63, 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.
氧化应激和亚硝化应激增加是慢性心力衰竭（CHF）患者左心室（LV）和血管功能障碍的重要介质。本研究调查了阿法达贝泊汀对CHF合并贫血患者氧化应激和亚硝化应激血浆标志物的影响。30例CHF患者（左心室射血分数[LVEF]<40%，血红蛋白<12.5 g/dl，血清肌酐<2.5 mg/dl）被随机分配（1:1）接受每20天1.5μg/kg的3个月阿法达贝泊汀方案加口服铁剂，或安慰剂加口服铁剂。在基线和治疗后评估血浆B型利钠肽（BNP）、氧化应激标志物（氧化、丙二醛、羰基蛋白；抗氧化、谷胱甘肽）和亚硝化应激标志物（硝基酪氨酸）、LVEF和6分钟步行距离。仅在接受阿法达贝泊汀治疗的患者中观察到LVEF和6分钟步行距离有显著改善。阿法达贝泊汀治疗后，血浆BNP（F = 14.8，p = 0.01）、丙二醛（F = 9.4，p = （此处原文有误，应为0.006））、蛋白质羰基（F = 9.2，p = 0.006）和硝基酪氨酸（F = 4.4，p = 0.045）显著降低，同时抗氧化谷胱甘肽增加（F = 4.2，p = 0.049）。这些因素在接受安慰剂治疗的患者中未受影响。阿法达贝泊汀诱导的羰基蛋白变化百分比与血浆BNP（r = 0.55，p <0.05）和LVEF（r = -0.46，p <0.05）的相应变化显著相关。最后，药物诱导的硝基酪氨酸降低百分比与6分钟步行距离的相应改善显著相关（r = -0.63，p <0.05）。总之，阿法达贝泊汀减轻了氧化应激和亚硝化应激对CHF贫血患者心血管系统的有害影响，同时改善了心脏功能和运动能力。
