on October 4, 2004
Published online before print October 4, 2004, doi: 10.1161/01.CIR.0000144303.24894.1C
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 14, 2003
From Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany. * To whom correspondence should be addressed. E-mail: Landmesser.Ulf{at}MH-Hannover.de.
Background--Accumulating evidence suggests a critical role for increased reactive oxygen species (ROS) production in left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI). Increased expression of xanthine oxidase (XO), a major source of ROS, has recently been demonstrated in experimental and clinical heart failure; however, a potential role for LV remodeling processes remains unclear. We therefore studied the effect of long-term treatment with allopurinol, a potent XO inhibitor, on myocardial ROS production and LV remodeling and dysfunction after MI. Methods and Results--Mice with extensive anterior MI (n=105) were randomized to treatment with either vehicle or allopurinol (20 mg · kg-1 · d-1 by gavage) for 4 weeks starting on day 1 after surgery. Infarct size was similar among the groups. XO expression and activity were markedly increased in the remote myocardium of mice after MI, as determined by electron spin resonance spectroscopy. Myocardial ROS production was increased after MI but markedly reduced after allopurinol treatment. Importantly, allopurinol treatment substantially attenuated LV cavity dilatation and dysfunction after MI, as assessed by echocardiography, and markedly reduced myocardial hypertrophy and interstitial fibrosis. Conclusion--The present study reveals a novel beneficial effect of treatment with allopurinol, ie, a marked attenuation of LV remodeling processes and dysfunction after experimental MI. Allopurinol treatment therefore represents a potential novel strategy to prevent LV remodeling and dysfunction after MI.
Revised on June 8, 2004
Accepted on July 20, 2004
Allopurinol Attenuates Left Ventricular Remodeling and Dysfunction After Experimental Myocardial Infarction. A New Action for an Old Drug?
Niels Engberding MD,
Key words: remodeling • free radicals • heart failure
This article has been cited by other articles:
 |
|
 |
|
  J. M. Hare, B. Mangal, J. Brown, C. Fisher Jr, R. Freudenberger, W. S. Colucci, D. L. Mann, P. Liu, M. M. Givertz, R. P. Schwarz, et al. Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study. J. Am. Coll. Cardiol., June 17, 2008; 51(24): 2301 - 2309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Boueiz, M. Damarla, and P. M. Hassoun Xanthine oxidoreductase in respiratory and cardiovascular disorders Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L830 - L840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Hemnes, A. Zaiman, and H. C. Champion PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L24 - L33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Yamamoto, K. Kataoka, T. Yamashita, Y. Tokutomi, Y.-F. Dong, S. Matsuba, H. Ogawa, and S. Kim-Mitsuyama Role of Xanthine Oxidoreductase in the Reversal of Diastolic Heart Failure by Candesartan in the Salt-Sensitive Hypertensive Rat Hypertension, October 1, 2007; 50(4): 657 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Seddon, Y. H Looi, and A. M Shah Oxidative stress and redox signalling in cardiac hypertrophy and heart failure Heart, August 1, 2007; 93(8): 903 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Takagawa, Y. Zhang, M. L. Wong, R. E. Sievers, N. K. Kapasi, Y. Wang, Y. Yeghiazarians, R. J. Lee, W. Grossman, and M. L. Springer Myocardial infarct size measurement in the mouse chronic infarction model: comparison of area- and length-based approaches J Appl Physiol, June 1, 2007; 102(6): 2104 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Doerries, K. Grote, D. Hilfiker-Kleiner, M. Luchtefeld, A. Schaefer, S. M. Holland, S. Sorrentino, C. Manes, B. Schieffer, H. Drexler, et al. Critical Role of the NAD(P)H Oxidase Subunit p47phox for Left Ventricular Remodeling/Dysfunction and Survival After Myocardial Infarction Circ. Res., March 30, 2007; 100(6): 894 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Takimoto and D. A. Kass Role of Oxidative Stress in Cardiac Hypertrophy and Remodeling Hypertension, February 1, 2007; 49(2): 241 - 248. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Casadei The emerging role of neuronal nitric oxide synthase in the regulation of myocardial function Exp Physiol, November 1, 2006; 91(6): 943 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hilfiker-Kleiner, U. Landmesser, and H. Drexler Molecular Mechanisms in Heart Failure: Focus on Cardiac Hypertrophy, Inflammation, Angiogenesis, and Apoptosis J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A56 - A66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Murdoch, M. Zhang, A. C. Cave, and A. M. Shah NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure Cardiovasc Res, July 15, 2006; 71(2): 208 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, A. Nivorozhkin, and C. Szabo Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol. Rev., March 1, 2006; 58(1): 87 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Daghini, A. R. Chade, J. D. Krier, D. Versari, A. Lerman, and L. O. Lerman Acute inhibition of the endogenous xanthine oxidase improves renal hemodynamics in hypercholesterolemic pigs Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R609 - R615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Minhas, R. M. Saraiva, K. H. Schuleri, S. Lehrke, M. Zheng, A. P. Saliaris, C. E. Berry, K. M. Vandegaer, D. Li, and J. M. Hare Xanthine Oxidoreductase Inhibition Causes Reverse Remodeling in Rats With Dilated Cardiomyopathy Circ. Res., February 3, 2006; 98(2): 271 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Naumova, V. P. Chacko, R. Ouwerkerk, L. Stull, E. Marban, and R. G. Weiss Xanthine oxidase inhibitors improve energetics and function after infarction in failing mouse hearts Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H837 - H843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Dawson, C. A. Lygate, M.-H. Zhang, K. Hulbert, S. Neubauer, and B. Casadei nNOS Gene Deletion Exacerbates Pathological Left Ventricular Remodeling and Functional Deterioration After Myocardial Infarction Circulation, December 13, 2005; 112(24): 3729 - 3737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Saraiva, K. M. Minhas, S. V.Y. Raju, L. A. Barouch, E. Pitz, K. H. Schuleri, K. Vandegaer, D. Li, and J. M. Hare Deficiency of Neuronal Nitric Oxide Synthase Increases Mortality and Cardiac Remodeling After Myocardial Infarction: Role of Nitroso-Redox Equilibrium Circulation, November 29, 2005; 112(22): 3415 - 3422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Duncan, R. Ravi, L. B. Stull, and A. M. Murphy Chronic xanthine oxidase inhibition prevents myofibrillar protein oxidation and preserves cardiac function in a transgenic mouse model of cardiomyopathy Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1512 - H1518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. R. Paiva, R. Novo, B. B. Matsubara, L. S. Matsubara, P. S. Azevedo, M. F. Minicucci, A. O. Campana, and L. A. M. Zornoff {beta}-Carotene Attenuates the Paradoxical Effect of Tobacco Smoke on the Mortality of Rats after Experimental Myocardial Infarction J. Nutr., September 1, 2005; 135(9): 2109 - 2113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Mellin, M. Isabelle, A. Oudot, C. Vergely-Vandriesse, C. Monteil, B. Di Meglio, J. P. Henry, B. Dautreaux, L. Rochette, C. Thuillez, et al. 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 Eur. Heart J., August 1, 2005; 26(15): 1544 - 1550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kittleson and J. M. Hare Xanthine oxidase inhibitors: an emerging class of drugs for heart failure Eur. Heart J., August 1, 2005; 26(15): 1458 - 1460. [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. McNally, A. Saxena, H. Cai, S. Dikalov, and D. G. Harrison Regulation of Xanthine Oxidoreductase Protein Expression by Hydrogen Peroxide and Calcium Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1623 - 1628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W Doehner and S D Anker Xanthine oxidase inhibition for chronic heart failure: is allopurinol the next therapeutic advance in heart failure? Heart, June 1, 2005; 91(6): 707 - 709. [Abstract] [Full Text] [PDF]
|
|