Allopurinol therapy of ischemic heart disease with infarct extension.
OBJECTIVE
Free radicals produced by the hypoxanthine-xanthine oxidase reaction in ischemia/reperfusion experiments have been proposed as contributing to myocardial cell necrosis in acute myocardial infarction. In this study, the hypothesis was tested that a commonly observed late phase of necrosis, infarct extension, could be prevented by allopurinol, an inhibitor of xanthine oxidase.


METHODS
Allopurinol, a xanthine oxidase inhibitor, was used with placebo in a double-blind randomized therapy study in 140 patients with ischemic heart disease admitted to the authors' hospital. Eighty-four had acute myocardial infarction and the remaining 56 had unstable angina. Of the 84 patients with infarction, 39 received allopurinol treatment. If xanthine oxidase production of cytotoxic free radical plays a major role in the pathogenesis of infarct extension, blockade of the reaction with allopurinol should decrease the occurrence of extension.


RESULTS
Nineteen infarct extensions were observed; five (11%) in the placebo group and 14 (36%) in the allopurinol.


CONCLUSIONS
The increased incidence of extension (P less than 0.007) in the treatment group does not support the hypothesis that xanthine oxidase contributes to infarct extension, which is consistent with recent reports that xanthine oxidase is not a significant component of the human myocardium. These findings indicate that allopurinol may actually be contraindicated in patients with ischemic heart disease.
Parmley
L F
LF
Department of Medicine, College of Medicine, University of South Alabama, Mobile 36617.
Mufti
A G
AG
Downey
J M
JM
D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use*; D000789:Angina, Unstable / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003402:Creatine Kinase / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009336:Necrosis; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D005609:Free Radicals; D007527:Isoenzymes; D000493:Allopurinol; D014969:Xanthine Oxidase; D003402:Creatine Kinase