Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion.
Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion.
复制标题
奥嘌呤醇限制心肌顿抑，但不会减少再灌注后的梗塞面积。
DOI：
10.1161/01.cir.76.3.678
复制
发表时间：
1987
期刊：
影响因子：
37.8
通讯作者：
Virmani,R
中科院分区：
文献类型：
--
作者：
Puett,DW;Forman,MB;Cates,CU;Wilson,BH;Hande,KR;Friesinger,GC;Virmani,R
为了探讨由黄嘌呤氧化酶途径产生的氧自由基对梗死面积和左心室功能的作用，在90分钟的闭胸犬闭塞-再灌注准备中评估了别嘌呤醇的活性代谢物和黄嘌呤氧化酶的有效非竞争性抑制剂羟嘌呤醇的作用。在闭塞后60分钟，动物随机接受25 mg/kg静脉注射奥昔嘌呤醇（n = 13）或生理盐水（n = 13）。用放射性微球测定局部心肌血流量，用心室造影测定局部心室功能。两组的血流动力学变量、局部心肌血流量和闭塞床的大小相似。再灌注后24小时，当以危险面积的百分比表示时，奥昔嘌呤醇未能减少梗死面积（36.3 +/- 4.9% vs 36.0 +/- 5.6%; p = NS）。两组在基线时均表现出相当的桡骨短缩，闭塞后1小时的运动障碍程度相似（-6.6 +/- 1.2% vs -4.9 +/- 1.0%）。然而，再灌注后3小时，经氧代嘌呤醇治疗的动物显示局部心室功能改善（0.7 +/- 2.6% vs -2.8 +/- 2.0%），24小时时显著改善（5.4 +/- 2.5% vs -3.2 +/- 1.7%; p <0.05）。在给药动物的边界区观察到中性粒细胞浸润减少。这些研究结果表明，氧自由基来自黄嘌呤氧化酶途径有助于可逆性损伤心肌顿抑，但不确定在犬制备的再灌注心肌坏死的最终程度。
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.