Allopurinol improves endothelial dysfunction in chronic heart failure
Allopurinol improves endothelial dysfunction in chronic heart failure
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DOI：
10.1161/01.cir.0000022140.61460.1d
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发表时间：
2002-07-09
期刊：
影响因子：
37.8
通讯作者：
Struthers, AD
中科院分区：
文献类型：
--
作者：
Farquharson, CA;Butler, R;Struthers, AD
慢性心力衰竭中氧化应激的增加被认为是内皮功能障碍的原因。黄嘌呤氧化酶产生氧化应激，因此，我们研究了是否别嘌呤醇改善内皮功能障碍，在慢性heartfailure.Methods和结果，我们进行了一项随机，安慰剂对照，双盲交叉研究I I患者与纽约心脏协会II-III级慢性心力衰竭，比较300毫克别嘌呤醇每天（一个月）与安慰剂。内皮功能通过标准前臂静脉闭塞体积描记法用乙酰胆碱、硝普钠和维拉帕米进行评估。还比较了血浆丙二醛水平，以评估氧化应激的显著变化。别嘌呤醇显著增加了前臂血流对乙酰胆碱的反应（前臂血流变化百分比[均值-SEM]：别嘌呤醇与安慰剂相比为181 +/- 19% vs 120 +/- 2%; P=0.003）。对于硝普钠或维拉帕米，安慰剂和别嘌呤醇治疗组之间的前臂血流变化无显著差异。血浆丙二醛显着降低别嘌呤醇治疗（346 +/- 128 nmol/L与461 +/- 101 nmol/L，别嘌呤醇与安慰剂; P=0.03），与降低氧化应激与别嘌呤醇therapy. Conclusions，我们已经表明，别嘌呤醇改善慢性心力衰竭内皮功能障碍。这提出了别嘌呤醇可能减少心血管事件，甚至改善慢性心力衰竭患者运动能力的明显可能性。
Background-Increased oxidative stress in chronic heart failure is thought to contribute to endothelial dysfunction. Xanthine oxidase produces oxidative stress and therefore we examined whether allopurinol improved endothelial dysfunction in chronic heart failure.Methods and Results-We performed a randomized, placebo-controlled, double-blind crossover study on I I patients with New York Heart Association class II-III chronic heart failure, comparing 300 mg allopurinol daily (I month) versus placebo. Endothelial function was assessed by standard forearm venous occlusion plethysmography with acetylcholine, nitroprusside, and verapamil. Plasma malondialdehyde levels were also compared to assess significant changes in oxidative stress. Allopurinol significantly increased the forearm blood flow response to acetylcholine (percentage change in forearm blood flow [mean-SEM]: 181 +/- 19% versus 120 +/- 2% allopurinol versus placebo; P=0.003). There were no significant differences in the forearm blood flow changes between the placebo and allopurinol treatment arms with regard to sodium nitroprusside or verapamil. Plasma malondialdehyde was significantly reduced with allopurinol treatment (346 +/- 128 nmol/L versus 461 +/- 101 nmol/L, allopurinol versus placebo; P=0.03), consistent with reduced oxidative stress with allopurinol therapy.Conclusions-We have shown that allopurinol improves endothelial dysfunction in chronic heart failure. This raises the distinct possibility that allopurinol might reduce cardiovascular events and even improve exercise capacity in chronic heart failure.