Allopurinol, xanthine oxidase, and cardiac ischemia.
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 micromol/L or less over a period of 3 years. Comparing this to a 27% mortality rate in patients with UA levels 400 micromol/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.
Michigan State University/Kalamazoo Center for Medical Studies, Kalamazoo, MI 49008, USA.
Brian E
BE
Lee
Alexander H
AH
Toledo
Roberto
R
Anaya-Prado
Richard R
RR
Roach
Luis H
LH
Toledo-Pereyra
D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000493:Allopurinol; D014969:Xanthine Oxidase