Chin Bernard S P, Gibbs Christopher R, Blann Andrew D, Lip Gregory Y H
Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK.
Clin Sci (Lond). 2003 Oct;105(4):507-12. doi: 10.1042/CS20030172.
We hypothesized that abnormal oxidative stress in chronic heart failure (CHF) could be related to endothelial damage and platelet activation, and that the vasodilating beta-blocker carvedilol would have beneficial effects on these processes compared with a selective non-vasodilating cardioselective beta-blocker, bisoprolol. We therefore assessed the effects of introducing carvedilol and bisoprolol in a prospective manner on indices of oxidative stress [lipid hydroperoxides (LHP)], endothelial damage [von Willebrand factor (vWf)], platelet activation (soluble P-selectin) and coagulation (fibrinogen) and their inter-relationships in stable outpatients with CHF in sinus rhythm. We recruited 46 patients [23 male; age 64 +/- 13 years (mean +/- S.D.); range 38-85 years] with CHF. Baseline levels of serum LHP (P<0.002), plasma vWf (P<0.001) and soluble P-selectin (P=0.02), but not fibrinogen (P=0.16), were higher in CHF patients compared with 22 age- and sex-matched healthy controls. After treatment for 2 months, systolic blood pressure fell in both arms of the study (both P<0.01), but there were no statistically significant (defined as P<0.01) decreases in LHP, vWf, fibrinogen or soluble P-selectin levels with either carvedilol or bisoprolol. In conclusion, patients with CHF have increased levels of plasma LHP and vWf, indicating increased oxidative stress and endothelial damage respectively. Contrary to the proposed antioxidative effects of carvedilol, initiating and titrating such therapy did not result in a reduction in levels of LHP in CHF.
我们推测,慢性心力衰竭(CHF)中异常的氧化应激可能与内皮损伤和血小板活化有关,并且与选择性非血管扩张性心脏选择性β受体阻滞剂比索洛尔相比,血管扩张性β受体阻滞剂卡维地洛可能对这些过程具有有益作用。因此,我们以前瞻性方式评估了在窦性心律的稳定CHF门诊患者中引入卡维地洛和比索洛尔对氧化应激指标[脂质氢过氧化物(LHP)]、内皮损伤[血管性血友病因子(vWf)]、血小板活化(可溶性P选择素)和凝血(纤维蛋白原)及其相互关系的影响。我们招募了46例CHF患者[23例男性;年龄64±13岁(均值±标准差);范围38 - 85岁]。与22名年龄和性别匹配的健康对照相比,CHF患者血清LHP(P<0.002)、血浆vWf(P<0.001)和可溶性P选择素(P = 0.02)的基线水平较高,但纤维蛋白原(P = 0.16)并非如此。治疗2个月后,研究的两组患者收缩压均下降(均P<0.01),但使用卡维地洛或比索洛尔治疗后,LHP、vWf、纤维蛋白原或可溶性P选择素水平均无统计学意义的下降(定义为P<0.01)。总之,CHF患者血浆LHP和vWf水平升高,分别表明氧化应激增加和内皮损伤增加。与卡维地洛所提出的抗氧化作用相反,启动并滴定这种治疗并未导致CHF患者LHP水平降低。