Effect of a selective aldosterone receptor antagonist in myocardial infarction
Effect of a selective aldosterone receptor antagonist in myocardial infarction
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DOI：
10.1152/ajpheart.2001.281.2.h647
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发表时间：
2001-08-01
影响因子：
4.8
通讯作者：
Rudolph, AE
中科院分区：
文献类型：
--
作者：
Delyani, JA;Robinson, EL;Rudolph, AE
心肌梗死（MI）启动适应性组织重塑，这对心脏功能（如梗死愈合）至关重要，但对适应不良重塑（如反应性纤维化和左心室扩张）也很重要。使用依普利酮（一种选择性醛固酮受体拮抗剂）在Sprague-Dawley大鼠中评价醛固酮受体拮抗剂对这些过程的影响。在MI后3、7和28天通过测定左心室舒张压-容积关系、梗死变薄率和胶原体积分数来评价心肌梗死愈合和左心室重构。依普利酮并不影响修复性胶原沉积，这一点可以通过在MI后7天和28天依普利酮和溶媒治疗组之间梗死心肌中相似的胶原体积分数来证明。此外，在MI后7天和28天，依普利酮和赋形剂治疗的动物之间的变薄比率（其是梗塞扩展的指数）是相当的。依普利酮的保护作用在MI后28天得到证实，其中与载体治疗的动物相比，依普利酮治疗的动物中存活心肌中的反应性纤维化减少。因此，醛固酮受体拮抗剂并不延缓梗死愈合，而是保护心肌梗死后的适应不良反应。
Myocardial infarction (MI) initiates adaptive tissue remodeling, which is essential for heart function (such as infarct healing) but is also important for maladaptive remodeling (for example, reactive fibrosis and left ventricular dilation). The effect of aldosterone receptor antagonism on these processes was evaluated in Sprague-Dawley rats using eplerenone, a selective aldosterone receptor antagonist. Infarct healing and left ventricular remodeling were evaluated at 3, 7, and 28 days after MI by determination of the diastolic pressure-volume relationship of the left ventricle, the infarct-thinning ratio, and the collagen-volume fraction. Eplerenone did not affect reparative collagen deposition as was evidenced by a similar collagen volume fraction in the infarcted myocardium between eplerenone and vehicle-treated groups at 7 and 28 days post-MI. In addition, the thinning ratio, which is an index of infarct expansion, was comparable between the eplerenone and vehicle-treated animals at 7 and 28 days post-MI. A protective effect of eplerenone was demonstrated at 28 days post-MI, where reactive fibrosis in the viable myocardium was reduced in eplerenone-treated animals compared with vehicle-treated animals. Thus aldosterone receptor antagonism does not retard infarct healing but rather protects against maladaptive responses after MI.