Charlat M I, O'Neill P G, Egan J M, Abernethy D R, Michael L H, Myers M L, Roberts R, Bolli R
Am J Physiol. 1987 Mar;252(3 Pt 2):H566-77. doi: 10.1152/ajpheart.1987.252.3.H566.
Recent evidence suggests that postischemic myocardial dysfunction (or myocardial "stunning") may be mediated by oxygen free radicals, but the mechanism for their production remains unknown. To explore the role of xanthine oxidase as a potential source of free radicals, open-chest dogs undergoing a 15-min occlusion of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion (REP) received intravenously either allopurinol (50 mg/kg 48 h, 20 h, and 30 min before occlusion, 10 mg/kg 1 min before REP, and 6.25 mg X kg-1 X h-1 throughout REP, n = 13) or saline (n = 14). The two groups were similar with respect to occluded bed size (postmortem perfusion) and collateral flow (radioactive microspheres). In controls, the transcardiac difference in plasma uric acid (great cardiac vein - arterial concentration) increased 199 +/- 70% (means +/- SE) during ischemia (P less than 0.02) and remained elevated for 5 min after REP; no increase was observed in treated dogs. Regional myocardial function was assessed by measuring systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under base-line conditions and similar degrees of dyskinesis during ischemia. Following REP, however, recovery of contractile function (expressed as percent of preocclusion values) was considerably greater in allopurinol-treated as compared with control dogs: 57 +/- 14 vs. -22 +/- 16 (P less than 0.01) at 1 h, 70 +/- 13 vs. -15 +/- 15 (P less than 0.001) at 2 h, 65 +/- 14 vs. -28 +/- 13 (P less than 0.001) at 3 h, and 68 +/- 13 vs. -17 +/- 14 (P less than 0.001) at 4 h. These differences could not be ascribed to hemodynamic factors. The results suggest that xanthine oxidase is a source of the oxygen free radicals responsible for myocardial stunning following a brief episode of reversible regional ischemia.
最近有证据表明，缺血后心肌功能障碍（或心肌“顿抑”）可能由氧自由基介导，但其产生机制尚不清楚。为了探讨黄嘌呤氧化酶作为自由基潜在来源的作用，对开胸犬进行15分钟的左前降支冠状动脉（LAD）闭塞，随后再灌注4小时（REP），在闭塞前48小时、20小时和30分钟静脉注射别嘌呤醇（50mg/kg），再灌注前1分钟静脉注射10mg/kg，再灌注期间持续静脉注射6.25mg·kg⁻¹·h⁻¹（n = 13），另一组静脉注射生理盐水（n = 14）。两组在闭塞床大小（尸检灌注）和侧支血流（放射性微球）方面相似。在对照组中，缺血期间血浆尿酸的跨心脏差异（大冠状静脉 - 动脉浓度）增加了199±70%（均值±标准误）（P<0.02），再灌注后5分钟仍保持升高；治疗组犬未观察到增加。通过用体表多普勒探头测量收缩期壁增厚来评估局部心肌功能。两组在基线条件下表现出相当的收缩期增厚，缺血期间运动障碍程度相似。然而，再灌注后，与对照组犬相比，别嘌呤醇治疗组的收缩功能恢复（以闭塞前值的百分比表示）明显更大：1小时时为57±14 vs -22±16（P<0.01），2小时时为70±13 vs -15±15（P<0.001），3小时时为65±14 vs -28±13（P<0.001），4小时时为68±13 vs -17±14（P<0.001）。这些差异不能归因于血流动力学因素。结果表明，黄嘌呤氧化酶是短暂可逆性局部缺血后导致心肌顿抑的氧自由基来源。
