Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways
Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways
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DOI：
10.1016/j.jacc.2004.05.060
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发表时间：
2004-09-01
影响因子：
24
通讯作者：
Cohen, MV
中科院分区：
文献类型：
--
作者：
Yang, XM;Proctor, JB;Cohen, MV
背景最近证实，在犬中进行的后处理挽救了缺血心肌。方法对照心脏进行30分钟的局部缺血/3小时的再灌注，而在实验心脏中，四个30秒闭塞/30秒闭塞的后处理周期，结果：后处理使对照组心肌梗死危险区从35.4 ± 2.7%降低到19.8 ± 2.7%。- 1.8%（p < 0.05）。六个周期并没有产生更大的保护作用。如果再灌注10分钟后开始后处理循环，则保护作用不再明显。在再灌注前5分钟给予非选择性K-ATP通道封闭剂格列本脲或选择性线粒体K-ATP通道拮抗剂5-羟基癸酸酯阻断后处理提供的保护，表明线粒体K，T通道参与。PD 98059，一种促分裂原活化蛋白/细胞外信号调节激酶（MEK）1/2，因此细胞外信号调节激酶（ERK）抑制剂，和N-ω-硝基-L-精氨酸甲酯，一氧化氮合酶的拮抗剂，再灌注前不久注入也中止了后处理提供的保护。缺血后处理和预处理相结合，导致显着更大的保护比任何单独。结论多个，短，区域冠状动脉闭塞后立即长期心肌缺血是一种有效的心脏保护干预在兔，和保护机制涉及ERK激活，一氧化氮的产生，和线粒体K-ATP通道开放。这些观察结果表明，类似的方法可以应用于心脏导管实验室，以保护急性心肌梗死患者直接血管成形术后的再灌注心肌。(C)2004年，美国心脏病学会基金会。
OBJECTIVES An in situ model was used to test whether and how multiple occlusions at reperfusion can protect rabbit myocardium.BACKGROUND Recently it was demonstrated that postconditioning in dogs salvaged ischernic myocardium.METHODS Control hearts underwent 30-min regional ischemia/3-h reperfusion, whereas in experimental hearts four postconditioning cycles of 30-s occlusion/30-s reperfusion starting 30 s after release of the index coronary occlusion were added in the presence or absence of various cell signaling antagonists.RESULTS Postconditioning decreased infarction from 35.4 +/- 2.7% of the risk zone in control hearts to 19.8 +/- 1.8% (p < 0.05). Six cycles did not result in greater protection. If postconditioning cycles were begun after 10 min of reperfusion, protection was no longer evident. Either the non-selective K-ATP channel closer glibenclamide or the putatively selective mitochondrial K-ATP channel antagonist 5-hydroxydecanoate administered 5 min before reperfusion blocked the protection afforded by postconditioning, indicating involvement of the mitochondrial K,T, channel. PD98059, a mitogen-activated protein/extracellular- signal regulated kinase (MEK) 1/2 and therefore extracellular-signal regulated kinase (ERK) inhibitor, and N-omega-nitro-L-arginine methyl ester, an antagonist of nitric oxide synthase, infused shortly before reperfusion also aborted the protection afforded by postconditioning. Combined ischernic postconditioning and preconditioning resulted in significantly greater protection than either alone.CONCLUSIONS Multiple, short, regional coronary occlusions immediately after prolonged myocardial ischemia are an efective cardioprotective intervention in the rabbit, and the mechanism of protection involves activation of ERK, production of nitric oxide, and opening of mitochondrial K-ATP channels. These observations suggest that a similar approach could be applied in the cardiac catheterization laboratory to protect reperfused myocardium after primary angioplasty in patients with acute myocardial infarction. (C) 2004 by the American College of Cardiology Foundation.