Direct evidence that the hydroxyl radical plays a pathogenetic role in myocardial "stunning" in the conscious dog and demonstration that stunning can be markedly attenuated without subsequent adverse effects.
Direct evidence that the hydroxyl radical plays a pathogenetic role in myocardial "stunning" in the conscious dog and demonstration that stunning can be markedly attenuated without subsequent adverse effects.
复制标题
直接证据表明羟自由基在清醒狗的心肌“击晕”中发挥致病作用，并证明击晕可以显着减弱而不会产生后续不良反应。
DOI：
10.1161/01.res.73.4.705
复制
发表时间：
1993
影响因子：
20.1
通讯作者：
Bolli,R
中科院分区：
文献类型：
--
作者：
Sekili,S;McCay,PB;Li,XY;Zughaib,M;Sun,JZ;Tang,L;Thornby,JI;Bolli,R
最近的研究表明，羟基自由基（.OH）在缺血后心室功能障碍（心肌“顿抑”）中起致病作用。然而，这一概念仅基于麻醉开胸准备中获得的结果，这些结果受到许多非生理条件的混淆影响，并且其中心肌顿抑和自由基产生都被大大夸大。在更多的生理动物模型中缺乏支持性证据，这是.OH致晕假说的主要局限性。此外，人们还担心心肌顿抑可能是完全恢复所必需的“休息”期，因此抗氧化剂治疗对早期顿抑的减弱可能对静息功能和/或心肌收缩储备的恢复产生后续有害影响。为了解决这些问题，在本研究的第1阶段中，经历15分钟冠状动脉闭塞的清醒的未镇静的狗接受生理盐水（n = 22）、.OH清除剂N-2-巯基丙酰甘氨酸（MPG，n = 17）或铁螯合剂去铁胺（DF，n = 14）的静脉内输注。与对照犬相比，MPG或DF治疗的犬在再灌注的前6小时内表现出明显更大的缺血后壁增厚;在此时间间隔内，MPG和DF使壁增厚的总缺陷减少了50%。这种有益效果的大小是缺血严重程度的函数，因此侧支血流最低的犬对室壁增厚的改善最大。MPG和DF在前6小时内产生的加速恢复在24或48小时时未引起静息壁增厚的任何恶化。此外，在MPG或DF治疗的犬中，最大变力性刺激引起的室壁增厚增加，（异丙肾上腺素或多巴胺）在昏迷前和静息室壁增厚正常化后不久相似（回流后24或48小时）;因此，尽管大多数早期缺血后功能障碍已被抗氧化剂治疗消除，静息功能或收缩储备没有随后的损害。在阶段2中，自由基的产生（用自旋捕获器α-苯基N-叔丁基硝酮测量）被与阶段1中减弱顿抑的相同剂量的MPG和DF显著抑制（> 80%）。（400字处截断摘要）
Recent studies suggest that the hydroxyl radical (.OH) plays a pathogenetic role in postischemic ventricular dysfunction (myocardial "stunning"). This concept, however, is predicated exclusively on results obtained in anesthetized open-chest preparations, which are subject to the confounding influence of many unphysiological conditions and in which both myocardial stunning and free radical generation are greatly exaggerated. The lack of supporting evidence in more physiological animal models represents a major limitation of the .OH hypothesis of stunning. Furthermore, concern has been raised that myocardial stunning may be a period of "rest" necessary for full recovery, so that attenuation of the early phase of stunning by antioxidant therapy may have subsequent detrimental effects on the resting function and/or on the return of myocardial contractile reserve. To address these issues, in phase 1 of this study conscious unsedated dogs undergoing a 15-minute coronary artery occlusion received an intravenous infusion of normal saline (n = 22), of the .OH scavenger N-2-mercaptopropionyl glycine (MPG, n = 17), or of the iron chelator desferrioxamine (DF, n = 14). Compared with control dogs, the dogs treated with MPG or DF exhibited significantly greater postischemic wall thickening throughout the first 6 hours of reperfusion; the total deficit of wall thickening during this time interval was reduced 50% by MPG and 50% by DF. The magnitude of this beneficial effect was a function of the severity of ischemia, so that the dogs with the lowest collateral flows had the greatest improvement of wall thickening. The accelerated recovery produced by MPG and DF in the first 6 hours was not followed by any deterioration of resting wall thickening at 24 or 48 hours. Furthermore, in dogs treated with MPG or DF, the increase in wall thickening elicited by maximal inotropic stimulation (isoproterenol or dopamine) was similar before stunning and shortly after resting wall thickening had normalized (24 or 48 hours after reflow); thus, despite the fact that most of the early postischemic dysfunction had been eliminated by antioxidant therapy, there was no subsequent impairment of either resting function or contractile reserve. In phase 2, production of free radicals (measured with the spin trap alpha-phenyl N-tert-butyl nitrone) was markedly (> 80%) inhibited by the same doses of MPG and DF that attenuated stunning in phase 1.(ABSTRACT TRUNCATED AT 400 WORDS)