Allopurinol improves endothelial dysfunction in chronic heart failure

Colin A. J. Farquharson, Robert Butler, Alexander Hill, Jill J. F. Belch, Allan D. Struthers

    Research output: Contribution to journalArticle

    377 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)221-226
    Number of pages6
    JournalCirculation
    Volume106
    Issue number2
    DOIs
    Publication statusPublished - Jul 2002

    Fingerprint

    Allopurinol
    Heart Failure
    Forearm
    Placebos
    Oxidative Stress
    Nitroprusside
    Verapamil
    Malondialdehyde
    Acetylcholine
    Plethysmography
    Xanthine Oxidase
    Double-Blind Method
    Cross-Over Studies
    Arm
    Therapeutics
    Exercise

    Keywords

    • Antioxidants
    • Heart failure
    • Exercise
    • Endothelium

    Cite this

    Farquharson, Colin A. J. ; Butler, Robert ; Hill, Alexander ; Belch, Jill J. F. ; Struthers, Allan D. / Allopurinol improves endothelial dysfunction in chronic heart failure. In: Circulation. 2002 ; Vol. 106, No. 2. pp. 221-226.
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    Allopurinol improves endothelial dysfunction in chronic heart failure. / Farquharson, Colin A. J.; Butler, Robert; Hill, Alexander; Belch, Jill J. F.; Struthers, Allan D.

    In: Circulation, Vol. 106, No. 2, 07.2002, p. 221-226.

    Research output: Contribution to journalArticle

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    AU - Farquharson, Colin A. J.

    AU - Butler, Robert

    AU - Hill, Alexander

    AU - Belch, Jill J. F.

    AU - Struthers, Allan D.

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    N2 - 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.

    AB - 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.

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