Aldosterone receptor blockade improves left ventricular remodeling and increases ventricular fibrillation threshold in experimental heart failure
Aldosterone receptor blockade improves left ventricular remodeling and increases ventricular fibrillation threshold in experimental heart failure
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DOI：
10.1016/s0008-6363(03)00251-7
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发表时间：
2003-06-01
影响因子：
10.8
通讯作者：
Saccà, L
中科院分区：
文献类型：
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作者：
Cittadini, A;Monti, MG;Saccà, L
目的：探讨醛固酮受体阻断在梗死后心力衰竭中的作用。方法：87只中度心肌梗死大鼠随机分为两组，一组不给药，另一组给卡侬酮（螺内酯的活性代谢物，20mg /kg/d），另一组给雷米普利（1mg /kg/d），或两种药物联合用药。治疗于冠脉结扎后1个月开始，持续4周。在基线和4周后进行超声心动图检查。在治疗期结束时，对左室插管、离体心脏研究、形态计量组织学、心肌去甲肾上腺素和SERCA-2 mRNA进行评估。结果：安慰剂组、卡雷诺酮组、雷米普利组和联合用药组的梗死面积分别为33 +/- 3,32 +/- 3,34 +/- 3,34 +/- 4%。Canrenone减轻左室重塑，改善左室收缩和舒张功能，并显著减少间质和血管周围纤维化。同时使用雷米普利治疗会增加这些效果。此外，心肌去甲肾上腺素含量降低，心室颤动阈值显著提高。SERCA-2水平保持不变。结论：Canrenone可减轻梗死后心力衰竭大鼠左室扩张和间质重塑，改善左室充盈动力学和收缩功能。雷米普利的加入给予进一步的心脏保护。Canrenone还能降低心肌去甲肾上腺素含量，增加心室颤动阈值。这些数据为RALES研究中观察到的猝死减少提供了一个潜在的解释。
Objectives: To investigate the effects of aldosterone receptor blockade in postinfarction heart failure. Methods: Eighty-seven rats with moderate myocardial infarction were randomized to receive either no drug or canrenone, the active metabolite of spironolactone, 20 mg/kg/day, or ramipril, 1 mg/kg/day, or a combination of the two drugs. Treatment was initiated 1 month after coronary ligation and lasted 4 weeks. Echocardiography was performed at baseline and after 4 weeks. LV catheterization, isolated heart studies, morphometric histology, myocardial norepinephrine and SERCA-2 mRNA were assessed at the end of the treatment period. Results: Infarct sizes were 33 +/- 3, 32 +/- 3, 34 +/- 3, and 34 +/- 4% in the placebo, canrenone, ramipril, and combination groups, respectively. Canrenone attenuated LV remodeling, improved LV systolic and diastolic function, and markedly reduced interstitial and perivascular fibrosis. These effects were increased by concomitant ramipril therapy. Moreover, myocardial norepinephrine content was decreased while ventricular fibrillation threshold significantly augmented by canrenone. SERCA-2 levels remained unchanged. Conclusions: Canrenone attenuated LV dilation and interstitial remodeling, and improved LV filling dynamics and systolic function in the rat model of postinfarction heart failure. Addition of ramipril conferred further cardioprotection. Canrenone also reduced myocardial norepinephrine content and increased ventricular fibrillation threshold. The data provide a potential explanation for the decreased sudden death observed in the RALES study.