European Heart Journal Advance Access originally published online on May 25, 2005
European Heart Journal 2005 26(15):1458-1460; doi:10.1093/eurheartj/ehi321
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org
Xanthine oxidase inhibitors: an emerging class of drugs for heart failure
Department of Medicine, Cardiology Division, Johns Hopkins University School of Medicine, Ross 1059, 720 Rutland Avenue, Baltimore, MD 21205, USA
* Corresponding author. Tel: +1 410 614 4161; fax: +1 443 287 7945. E-mail address: jhare@mail.jhmi.edu
This editorial refers to ‘Transient reduction in myocardial free oxygen radical levels is involved in the improved cardiac function and structure after long-term allopurinol treatment initiated in established chronic heart failure’
by V. Mellin et al., on page 1544
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Mellin et al.1 report that short- and long-term xanthine oxidase (XO) inhibition with allopurinol, initiated in rats with chronic heart failure due to myocardial infarction, improves cardiac haemodynamics and function and reverses left ventricular remodelling. Rats with established left ventricular dysfunction induced by left coronary artery ligation received a 5-day or 10-week treatment with allopurinol starting 18 or 8 weeks, respectively, after the initial injury. Both short- and long-term allopurinol treatment increased cardiac output without changing arterial pressure consistent with an afterload reducing effect, but only long-term allopurinol treatment reduced left ventricular end-diastolic pressure and the left ventricular time-constant of relaxation. Importantly, chronic allopurinol produced clear reverse remodelling, decreasing left-ventricular systolic and diastolic diameters, weight, and collagen density.
Interestingly, a reduction in reactive oxygen species determined using electron spin resonance spectroscopy was detectable only in the group receiving 5 days of allopurinol, and thiobarbituric acid reactive substances (TBARS)
Pathophysiological role of XO pathway in heart failure
Mechanoenergetic uncoupling
Interaction between XO and nitric oxide pathways
Vascular dysfunction
Anti-oxidant effect of XO inhibition
Pathophysiological and clinical roles of uric acid in heart failure
Clinical utility of XO inhibitors in heart failure
Conclusions
Acknowledgements
Conflict of interest
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Related articles in EHJ:
- Transient reduction in myocardial free oxygen radical levels is involved in the improved cardiac function and structure after long-term allopurinol treatment initiated in established chronic heart failure
- Virginie Mellin, Marc Isabelle, Alexandra Oudot, Catherine Vergely-Vandriesse, Christelle Monteil, Benoit Di Meglio, Jean Paul Henry, Brigitte Dautreaux, Luc Rochette, Christian Thuillez, and Paul Mulder
EHJ 2005 26: 1544-1550.[Abstract] [Full Text]
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