Heart failure after myocardial infarction - Altered excitation-contraction coupling

Article

关键词: SARCOPLASMIC-RETICULUM;    DILATED CARDIOMYOPATHY;    CALCIUM;    MUSCLE;    SPARKS;    NA+;    ORGANIZATION;    MECHANISMS;    CHANNELS;    CELLS;   

DOI  :  10.1161/hc3201.092285

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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