Adrenomedullin administration immediately after myocardial infarction ameliorates progression of heart failure in rats
Adrenomedullin administration immediately after myocardial infarction ameliorates progression of heart failure in rats
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DOI：
10.1161/01.cir.0000136085.34185.83
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发表时间：
2004-07-27
期刊：
影响因子：
37.8
通讯作者：
Eto, T
中科院分区：
文献类型：
--
作者：
Nakamura, R;Kato, J;Eto, T
背景-肾上腺髓质素(AM)在心脏组织中表达，急性心肌梗死(MI)患者血浆AM水平升高。本研究旨在探讨急性心肌梗死后即刻给予黄芪是否能抑制心力衰竭的进展。方法和结果：采用左冠状动脉结扎诱导大鼠急性心肌梗死后7d，立即给予1.0mug/h的黄芪或生理盐水灌胃，并于心肌梗死后9周进行检查。与生理盐水输注相比，AM输注显著提高了存活率(59%比81%；P<；0.05)和体重增加(32%；P<；0.01)，并降低了心脏重量(-28%；P<；0.01)、肺重量(-26%；P<；0.01)、左心室(LV)舒张末压力(11.4+/-2.0比4.0+/-0.6 mm Hg，平均值+/-扫描电子显微镜；P<；非梗死区LV胶原体积分数(-39%；P<；0.05)和内源性AM血浆水平(-38%；P<；0.05)，而不影响梗塞范围。为探讨黄芪的作用机制，另一组大鼠于心肌梗死后第7天处死。黄芪对心肌梗死后第7天的脏器重量和血流动力学参数无明显影响，但可显著降低尿异前列腺素排泄量(-61%；P<；0.01)和非梗死区左心室ACE(-31%；P<；0.05)和p22-Phox(-30%；P<；0.05)的mRNA水平。结论心肌梗死早期给予黄连素可明显改善心肌梗死大鼠存活时间，改善左室重构和心力衰竭进展。在AM输注期间，伴随着这种有益效果的是氧化应激和非梗死性左室壁血管紧张素转换酶基因表达的降低。
Background-Adrenomedullin ( AM) is expressed in cardiac tissue, and plasma AM levels increase in patients with acute myocardial infarction (MI). This study was performed to determine whether AM administration immediately after acute MI inhibits progression of heart failure in rats.Methods and Results-Rats were infused with 1.0 mug/h IP AM or saline over 7 days immediately after MI inducted by left coronary ligation and were examined 9 weeks after MI. Compared with the saline infusion, AM infusion significantly improved survival (59% versus 81%; P < 0.05) and body weight gain (32%; P < 0.01) and reduced heart weight (-28%; P < 0.01), lung weight (-26%; P < 0.01), left ventricular (LV) end-diastolic pressure (11.4 +/- 2.0 versus 4.0 +/- 0.6 mm Hg, mean+/- SEM; P < 0.01), collagen volume fraction of noninfarcted LV (-39%; P < 0.05), and plasma levels of endogenous rat AM (-38%; P < 0.05) without affecting infarct size. To investigate the mechanism of AM actions, another series of MI rats infused with AM were killed on day 7. AM infusion had no effect on organ weights and hemodynamic parameters on day 7 of MI but significantly reduced urinary excretion of isoprostane (-61%; P < 0.01) and noninfarcted LV mRNA levels of ACE (-31%; P < 0.05) and p22-phox (-30%; P < 0.05).Conclusions-AM administration during the early period of MI improved the survival and ameliorated progression of LV remodeling and heart failure. This beneficial effect was accompanied by reductions in oxidative stress and ACE mRNA expression in noninfarcted LV in the AM infusion period.