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Allopurinol, Xanthine Oxidase, and Cardiac Ischemia
  1. Brian E. Lee, BA*†,
  2. Alexander H. Toledo, MD,
  3. Roberto Anaya-Prado, MD§,
  4. Richard R. Roach, MD,
  5. Luis H. Toledo-Pereyra, MD, PhD*†
  1. From the *Michigan State University/Kalamazoo Center for Medical Studies, and †Western Michigan University, Kalamazoo, MI; ‡University of North Carolina in Chapel Hill, NC; and §Western Medical Center in Guadalajara, Mexico.
  1. Received January 26, 2009, and in revised form May 22, 2009.
  2. Accepted for publication August 16, 2009.
  3. Reprints: Luis H. Toledo-Pereyra, MD, PhD, Michigan State University/Kalamazoo Center for Medical Studies, 1000 Oakland Dr., Kalamazoo, MI 49008. E-mail: toledo{at}kcms.msu.edu.

Abstract

Allopurinol as an effective inhibitor of the enzyme xanthine oxidase (XO) has been used for several decades for the treatment of patients with gout and hyperuricemia. Because the inhibition of XO limits the formation of radical oxygen species as well as uric acid (UA) production, allopurinol has been used experimentally for the treatment of conditions associated with ischemia and reperfusion (I/R) injury.

Although there have been many ischemic organs treated in the laboratory with allopurinol, the heart has been of particular interest. Therefore, we emphasize our attention to the administration of XO inhibitors such as allopurinol on cardiac I/R as well as cardiac failure. Experimental data also support allopurinol as a possible consideration for biochemical support after acute myocardial infarction.

Anker and associates (Circulation. 2003;107:1991-1997) have observed a direct correlation between uric acid levels and mortality in treated heart failure patients. Anker and associates showed a 100% mortality rate in patients with UA levels 800 μmol/L or less over a period of 3 years. Comparing this to a 27% mortality rate in patients with UA levels 400 μmol/L or less over a period of 10 years, it seems that the suppression of XO activity ameliorates myocardial inefficiency, and poor vascular flow may present innovative contributions to the future treatment of I/R heart failure patients. Our review focuses on the role of allopurinol on ischemic hearts as well as those with added chronic heart failure.

Key Words
  • allopurinol
  • xanthine oxidase
  • cardiac ischemia
  • radical oxygen species
  • CHF
  • ATP

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