Circulation. 2002;106:221-226
Published online before print June 17, 2002, doi: 10.1161/01.CIR.0000022140.61460.1D
Published online before print June 17, 2002, doi: 10.1161/01.CIR.0000022140.61460.1D
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(Circulation. 2002;106:221.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Allopurinol Improves Endothelial Dysfunction in Chronic Heart Failure
From the Department of Clinical Pharmacology and Therapeutics (C.A.J.F., R.B., A.D.S.) and the Department of Medicine (A.H., J.J.F.B.), Ninewells Hospital and Medical School, Dundee, UK.
Correspondence to Prof A.D. Struthers, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY UK. E-mail a.d.struthers{at}dundee.ac.uk
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 11 patients with New York Heart Association class II-III chronic heart failure, comparing 300 mg allopurinol daily (1 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±22% 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.
Key Words: antioxidants • heart failure • exercise • endothelium
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