Heart failure after myocardial infarction - Altered excitation-contractioncoupling

Background-Heart failure (HF) frequently follows the occurrence of myocardi al infarction (MI). Questions about how HF develops and what cellular defec ts contribute to this dysfunction led to this study. Methods and Results-MI was induced in rats by coronary artery ligation. Cli nical examination of the post-MI (PMI) surviving animals indicated that the y were in overt HF by all measures. Cellular examination of the cardiomyocy tes by patch-clamp and confocal [Ca2+](i) imaging methods indicated that ce llular function was significantly compromised. At the single-cell level, [C a2+](i) transient amplitudes were reduced and contractions were decreased a nd slowed, although Ca2+ current (Ic,) remained unchanged. The excitation-c ontraction coupling (ECC) gain function measured as Delta [Ca2+](i)/I-Ca wa s significantly decreased. Ouabain, a cardiotonic steroid that blocks the N a+,K -ATPase and activates Ca2+ entry via cardiac Na+ channels, largely all eviated this defect. Conclusions-After MI, 1(Ca) becomes less able to trigger release of Ca2+ fr om the sarcoplasmic reticulum. This failure of ECC is a major factor contri buting to the development of contractile dysfunction and HF in PMI animals. The improved ECC gain, enhanced Ca2+ entry, and augmented Ca2+ signaling d ue to cardiotonic steroids contribute to the beneficial effects of these ag ents.