Circulation. 2002;105:2619-2624
Published online before print May 13, 2002, doi: 10.1161/01.CIR.0000017502.58595.ED
Published online before print May 13, 2002, doi: 10.1161/01.CIR.0000017502.58595.ED
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(Circulation. 2002;105:2619.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Effects of Xanthine Oxidase Inhibition With Allopurinol on Endothelial Function and Peripheral Blood Flow in Hyperuricemic Patients With Chronic Heart Failure
Results From 2 Placebo-Controlled Studies
From Clinical Cardiology, National Heart and Lung Institute, Imperial College School of Medicine (W.D., M.R., F.L.-L., A.J.S.C., S.D.A.), and the Department of Clinical Chemistry, Charing Cross Campus, Imperial College School of Medicine (D.V.P., D.A.R.), London, UK; and the Franz-Volhard-Klinik (Charité, Campus Berlin Buch) at Max Delbrück Centrum for Molecular Medicine, Berlin (W.D., S.D.A.), and the University of Leipzig, Division of Cardiology, Heart Center, Leipzig (N.S., G.S., R.H.), Germany.
Correspondence to Stefan D. Anker, MD, PhD, Clinical Cardiology, NHLI London, Dovehouse Street, London, SW3 6LY, UK. E-mail s.anker{at}ic.ac.uk
Background— In patients with chronic heart failure (CHF), hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow. It has been suggested that the causal link of this association is increased xanthine oxidase (XO)–derived oxygen free radical production and endothelial dysfunction. We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies.
Methods and Results— In 10 CHF patients with normal serum uric acid (UA) levels (315±42 µmol/L) and 9 patients with elevated UA (535±54 µmol/L), endothelium-dependent (acetylcholine infusion) and endothelium-independent (nitroglycerin infusion) vasodilation of the radial artery was determined. Coinfusion of allopurinol (600 µg/min) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients (P<0.05). In a double-blind, crossover design, hyperuricemic CHF patients were randomly allocated to allopurinol 300 mg/d or placebo for 1 week. In 14 patients (UA 558±21 µmol/L, range 455 to 743 µmol/L), treatment reduced UA by >120 µmol/L in all patients (mean reduction 217±15 µmol/L, P<0.0001). Compared with placebo, allopurinol improved peak blood flow (venous occlusion plethysmography) in arms (+24%, P=0.027) and legs (+23%, P=0.029). Flow-dependent flow improved by 58% in arms (P=0.011). Allantoin, a marker of oxygen free radical generation, decreased by 20% after allopurinol treatment (P<0.001). There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment (r=0.63, P<0.05).
Conclusions— In hyperuricemic CHF patients, XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically.
Key Words: heart failure • blood flow • endothelium
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