Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction
Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction
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DOI：
10.1161/01.cir.0000068340.96506.0f
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发表时间：
2003-05-27
期刊：
影响因子：
37.8
通讯作者：
Horie, M
中科院分区：
文献类型：
--
作者：
Hayashi, M;Tsutamoto, T;Horie, M
背景-醛固酮(ALD)已被证明通过激活局部的盐皮质激素受体刺激心肌胶原合成和成纤维细胞的增殖。为了评价盐皮质激素受体拮抗剂螺内酯对急性心肌梗死患者心肌梗死后左室重构的影响，将134例急性前壁心肌梗死患者随机分为血管重建组(n=65)和非模型组(n=69)。所有患者在血管重建术后立即给予血管紧张素转换酶(ACE)抑制剂和研究药物。分别于急性期和1个月后行左心室造影术评价左室重构。测量主动脉根部和冠状静脉窦的ALD。两组患者的基线特征包括心肌梗死面积和左心室功能均无差异。然而，与非MRA组相比，MRA组的左心室射血分数明显改善(46.0+/-0.6%比53.2+/-0.8%比46.5+/-0.8%比51.0+/-0.8%，P交互=0.012)。与非MRA组比较，MRA组LV舒张末容量指数显著降低(86.5±1.0~90.6±2.4，87.5±-1.3~106.8+/-3.5mL/m(2)，P交互作用=0.002)。血管紧张素转换酶抑制剂与血管紧张素转换酶抑制剂联合应用对心肌梗死后左室重构的预防作用明显优于血管紧张素转换酶抑制剂(P-交互作用=0.001)。结论：血管紧张素转换酶抑制剂联合血管紧张素转换酶抑制剂能更好地预防心肌梗死后左室重构，其机制可能与抑制胶原合成标志物有关。
Background-Aldosterone (ALD) has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors. In patients with acute myocardial infarction, we demonstrated that ALD was extracted through the infarct heart and extracting ALD-stimulated post-infarct left ventricular (LV) remodeling.Methods and Results-To evaluate the effect of mineralocorticoid receptor antagonist (MRA) spironolactone on post-infarct LV remodeling, 134 patients with first anterior acute myocardial infarction were randomly divided into the MRA (n=65) or non-MRA (n=69) groups after revascularization. All patients were administered angiotensin-converting enzyme (ACE) inhibitor and study drug just after revascularization. Left ventriculography with contrast medium was performed at the acute stage and after 1 month to evaluate LV remodeling. ALD was measured at aortic root and coronary sinus. There was no difference in the baseline characteristics including infarct size and LV performance between the two groups. However, LV ejection fraction was significantly improved in the MRA group compared with that in the non-MRA group (46.0+/-0.6% to 53.2+/-0.8% versus 46.5+/-0.8% to 51.0+/-0.8%, P-interaction=0.012). LV end-diastolic volume index was significantly suppressed in the MRA group compared with that in non-MRA group (86.5+/-1.0 to 90.6+/-2.4 versus 87.5+/-1.3 to 106.8+/-3.5 mL/m(2), P-interaction=0.002). Transcardiac extraction of ALD through the heart was significantly suppressed in the MRA group (P-interaction=0.001), and plasma procollagen type III aminoterminal peptide level, a biochemical marker of fibrosis, was significant lower in the MRA group compared with the non-MRA group (P-interaction=0.002).Conclusions-These findings indicate that MRA combined with ACE inhibitor can prevent post-infarct LV remodeling better than ACE inhibitor alone in association with the suppression of a marker of collagen synthesis.