ATTENUATION OF DYSFUNCTION IN THE POSTISCHEMIC STUNNED MYOCARDIUM BY DIMETHYLTHIOUREA
ATTENUATION OF DYSFUNCTION IN THE POSTISCHEMIC STUNNED MYOCARDIUM BY DIMETHYLTHIOUREA
复制标题
DOI：
10.1161/01.cir.76.2.458
复制
发表时间：
1987-08-01
期刊：
影响因子：
37.8
通讯作者：
ROBERTS, R
中科院分区：
文献类型：
--
作者：
BOLLI, R;ZHU, WX;ROBERTS, R
在可逆性局部缺血后再灌注心肌（“顿抑”心肌）中观察到的长期收缩功能障碍的机制尚不清楚。最近的研究表明，心肌顿抑可能是由氧自由基介导的，但涉及的确切分子种类仍然未知。因此，我们探讨了高细胞毒性的羟基自由基在局部缺血后功能障碍中的作用，通过使用二甲基硫脲（DMTU），一种有效的和高渗透性的羟基自由基清除剂。开胸犬冠状动脉左前降支闭塞15分钟，再灌注4小时，接受DMTU（0.5 g/kg，从闭塞前30分钟开始静脉注射45分钟，n = 14）或生理盐水（n = 15）。对照组和给药组犬在可能影响缺血后功能障碍的变量方面相当，包括心率、主动脉压、左心房压、动脉血气和血红蛋白浓度、闭塞床的大小（通过死后灌注测定）和侧支血流（通过放射性微球测定）。通过心外膜多普勒探头测量室壁增厚程度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，在缺血期间表现出相似程度的运动障碍。然而，在再灌注后，与对照犬相比，治疗犬的壁增厚（以基线的百分比表示）显著更大：53 ± 1.5%。9%（平均值±）。SEM）与9 . ±. 14（p < .03），1小时，55 . ±. 9%对23 .+-. 13%（p <0.05），2小时，60 . ±. 9%对28 .+-. 3小时时为14%（p < .05），67 . ±. 5%对36 .+-.因此，DMTU在收缩功能恢复方面产生显著和持续的改善。在浓度大于体内达到的血浆水平时，DMTU在体外不抑制过氧化氢或超氧阴离子。这些结果表明，短暂局部缺血后发生的心肌功能障碍部分是由羟自由基介导的。
The mechanism for the prolonged contractile dysfunction observed in myocardium reperfused after reversible regional ischemia ("stunned" myocardium) is unclear. Recent studies suggest that myocardial stunning may be mediated by oxygen-derived free radicals, but the precise molecular species involved remain unknown. Thus we explored the role of the highly cytotoxic hydroxyl radical in regional postischemic dysfunction by using dimethylthiourea (DMTU), an effective and highly permeable hydroxyl radical scavenger. Open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery followed by 4 hr of reperfusion received either DMTU (0.5 g/kg iv over 45 min starting 30 min before occlusion, n = 14) or saline (n = 15). Control and treated dogs were comparable with respect to variables that may affect postischemic dysfunction, including heart rate, aortic pressure, left atrial pressure, arterial blood gases and hemoglobin concentration, size of the occluded bed (determined by postmortem perfusion), and collateral blood flow (determined by radioactive microspheres). Regional myocardial function was assessed by measuring wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesis during ischemia. After reperfusion, however, wall thickening (expressed as percent of baseline) was considerably greater in treated as compared with control dogs: 53 .+-. 9% (mean .+-. SEM) vs 9 .+-. 14 (p < .03) at 1 hr, 55 .+-. 9% vs 23 .+-. 13% (p < .05) at 2 hr, 60 .+-. 9% vs 28 .+-. 14% (p < .05) at 3 hr, and 67 .+-. 5% vs 36 .+-. 13% (p < .05) at 4 hr. Thus DMTU produced a significant and sustained improvement in recovery of contractile function. In concentrations greater than the plasma levels attained in vivo, DMTU did not scavenge either hydrogen peroxide or superoxide anion in vitro. These results suggest that the myocardial dysfunction occuring after a brief episode of regional ischemia is mediated in part by the hydroxyl radical.