Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion.
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.
D000818:Animals; D003097:Collateral Circulation; D003326:Coronary Circulation; D004285:Dogs; D005260:Female; D005609:Free Radicals; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010117:Oxypurinol / Q000494:pharmacology / Q000627:therapeutic use*; D010477:Perfusion; D011743:Pyrimidines / Q000627:therapeutic use*; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D011743:Pyrimidines; D014969:Xanthine Oxidase; D010117:Oxypurinol