Fraccarollo Daniela, Galuppo Paolo, Sieweke Jan-Thorben, Napp L Christian, Grobbecker Paul, Bauersachs Johann
Klinik fuer Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
Beckman Coulter GmbH, Krefeld, Germany.
ESC Heart Fail. 2015 Sep;2(3):150-158. doi: 10.1002/ehf2.12053. Epub 2015 Jul 28.
The selective mineralocorticoid receptor (MR) antagonist eplerenone given early in patients with acute myocardial infarction (MI) improves clinical outcome, whereas little is known about the effectiveness of early spironolactone therapy. We aimed to compare the ability of eplerenone and spironolactone to promote cardiac repair after experimental MI.
Starting immediately after coronary artery ligation, C57BL/6J mice were treated with placebo, eplerenone, or spironolactone. At 7 days, treatment with eplerenone or spironolactone reduced thinning and expansion of healing infarct and improved early left ventricular chamber enlargement. Remarkably, eplerenone therapy resulted in significantly greater improvement than spironolactone of left ventricular contractile function and relaxation, associated with a more considerable leftward and downward shift of the pressure volume curve. Seven-day survival rate was significantly increased only in eplerenone treated mice. Moreover, eplerenone was superior to spironolactone in ameliorating neovessel formation in the injured myocardium. Optimized flow cytometry analysis of the monocyte differentiation marker Ly6C revealed predominant accumulation of Ly6C monocytes/macrophages at the site of ischemic injury during the early inflammatory phase in placebo-treated mice. In contrast, MR antagonism, especially by eplerenone, led to a skewing of the monocyte/macrophage population toward a higher frequency of healing promoting Ly6C cells.
The MR antagonist eplerenone versus spironolactone showed superior efficacy during the acute MI phase with more beneficial effects on survival, early cardiac dilation, and functional decline. Modulation of monocyte maturation and enhanced infarct neovessel formation appears to play a pivotal role.
在急性心肌梗死（MI）患者早期给予选择性盐皮质激素受体（MR）拮抗剂依普利酮可改善临床结局，而早期螺内酯治疗的有效性鲜为人知。我们旨在比较依普利酮和螺内酯在实验性心肌梗死后促进心脏修复的能力。
冠状动脉结扎后立即开始，对C57BL/6J小鼠给予安慰剂、依普利酮或螺内酯治疗。在第7天，依普利酮或螺内酯治疗减少了愈合梗死区的变薄和扩大，并改善了早期左心室腔扩大。值得注意的是，依普利酮治疗在左心室收缩功能和舒张功能方面的改善明显大于螺内酯，同时压力-容积曲线有更明显的向左下移位。仅依普利酮治疗的小鼠7天生存率显著提高。此外，在改善受损心肌的新生血管形成方面，依普利酮优于螺内酯。对单核细胞分化标志物Ly6C进行优化的流式细胞术分析显示，在安慰剂治疗的小鼠早期炎症阶段，缺血损伤部位主要积聚Ly6C单核细胞/巨噬细胞。相比之下，MR拮抗作用，尤其是依普利酮，导致单核细胞/巨噬细胞群体向促进愈合的Ly6C细胞频率更高的方向倾斜。
在急性心肌梗死阶段，MR拮抗剂依普利酮与螺内酯相比显示出更高的疗效，对生存、早期心脏扩张和功能衰退有更有益的影响。单核细胞成熟的调节和梗死区新生血管形成的增强似乎起着关键作用。
