Document Detail

Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion.
MedLine Citation:
PMID:  3621527     Owner:  NLM     Status:  MEDLINE    
To explore the role of oxygen free radicals produced by the xanthine oxidase pathway on infarct size and left ventricular function, the effect of oxypurinol, an active metabolite of allopurinol and a potent noncompetitive inhibitor of xanthine oxidase, was assessed in a 90 min, closed-chest, canine preparation of occlusion-reperfusion. Animals were randomized to receive 25 mg/kg iv oxypurinol (n = 13) or saline (n = 13) 60 min after occlusion. Regional myocardial blood flow was measured with radioactive microspheres and regional ventricular function with contrast ventriculography. Hemodynamic variables, regional myocardial blood flow, and size of the occluded bed were similar in the two groups. Oxypurinol failed to reduce infarct size 24 hr after reperfusion when expressed as a percentage of the area at risk (36.3 +/- 4.9% vs 36.0 +/- 5.6%; p = NS). Both groups exhibited comparative radial shortening at baseline and similar degrees of dyskinesia 1 hr into occlusion (-6.6 +/- 1.2% vs -4.9 +/- 1.0%). However, oxypurinol-treated animals demonstrated an improved regional ventricular function at 3 hr after reperfusion (0.7 +/- 2.6% vs -2.8 +/- 2.0%) and a significant improvement at 24 hr (5.4 +/- 2.5% vs -3.2 +/- 1.7%; p less than .05). A reduced neutrophil infiltrate was observed in the border zone in treated animals. These findings suggest that oxygen free radicals derived from the xanthine oxidase pathway contribute to stunning of reversibly damaged myocardium but do not determine the final extent of myocardial necrosis in a canine preparation of reperfusion.
D W Puett; M B Forman; C U Cates; B H Wilson; K R Hande; G C Friesinger; R Virmani
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  76     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1987 Sep 
Date Detail:
Created Date:  1987-10-07     Completed Date:  1987-10-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  678-86     Citation Subset:  AIM; IM    
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MeSH Terms
Collateral Circulation
Coronary Circulation*
Free Radicals
Heart / drug effects,  physiopathology*
Myocardial Infarction / drug therapy*,  pathology,  physiopathology
Myocardium / enzymology,  metabolism
Oxypurinol / pharmacology,  therapeutic use*
Pyrimidines / therapeutic use*
Xanthine Oxidase / metabolism
Grant Support
1R23HL-34628-01/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Free Radicals; 0/Pyrimidines; 2465-59-0/Oxypurinol; EC Oxidase

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