Heart failure after myocardial infarction -: Altered excitation-contraction coupling
Heart failure after myocardial infarction -: Altered excitation-contraction coupling
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DOI：
10.1161/hc3201.092285
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发表时间：
2001-08-07
期刊：
影响因子：
37.8
通讯作者：
Lederer, WJ
中科院分区：
文献类型：
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作者：
Gómez, AM;Guatimosim, S;Lederer, WJ
背景-心力衰竭（HF）经常伴随着心肌梗塞（MI）的发生。关于心力衰竭如何发生以及哪些细胞缺陷导致这种功能障碍的问题引发了这项研究。方法和结果-通过冠状动脉结扎在大鼠中诱导心肌梗死。对心肌梗死后（PMI）幸存动物的临床检查表明，从所有指标来看，它们都处于明显的心衰状态。通过膜片钳和共焦 [Ca2+](i) 成像方法对心肌细胞进行细胞检查表明细胞功能显着受损。在单细胞水平上，尽管 Ca2+ 电流 (Ic) 保持不变，但 [Ca2+](i) 瞬时幅度降低，收缩减少并减慢。以 Delta [Ca2+](i)/I-Ca 测量的兴奋-收缩耦合 (ECC) 增益函数显着降低。哇巴因是一种强心类固醇，可阻断 Na+,K -ATP 酶并通过心脏 Na+ 通道激活 Ca2+ 进入，在很大程度上缓解了这一缺陷。 结论：MI 后，1(Ca) 触发肌浆网释放 Ca2+ 的能力降低。 ECC 的失败是导致 PMI 动物出现收缩功能障碍和心力衰竭的一个主要因素。由于强心类固醇，ECC 增益的改善、Ca2+ 进入的增强以及 Ca2+ 信号传导的增强有助于这些药物的有益作用。
Background-Heart failure (HF) frequently follows the occurrence of myocardial infarction (MI). Questions about how HF develops and what cellular defects contribute to this dysfunction led to this study.Methods and Results-MI was induced in rats by coronary artery ligation. Clinical examination of the post-MI (PMI) surviving animals indicated that they were in overt HF by all measures. Cellular examination of the cardiomyocytes by patch-clamp and confocal [Ca2+](i) imaging methods indicated that cellular function was significantly compromised. At the single-cell level, [Ca2+](i) transient amplitudes were reduced and contractions were decreased and slowed, although Ca2+ current (Ic,) remained unchanged. The excitation-contraction coupling (ECC) gain function measured as Delta [Ca2+](i)/I-Ca was significantly decreased. Ouabain, a cardiotonic steroid that blocks the Na+,K -ATPase and activates Ca2+ entry via cardiac Na+ channels, largely alleviated this defect.Conclusions-After MI, 1(Ca) becomes less able to trigger release of Ca2+ from the sarcoplasmic reticulum. This failure of ECC is a major factor contributing to the development of contractile dysfunction and HF in PMI animals. The improved ECC gain, enhanced Ca2+ entry, and augmented Ca2+ signaling due to cardiotonic steroids contribute to the beneficial effects of these agents.