Heart Failure After Myocardial Infarction Altered Excitation-Contraction Coupling

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 (ICa) remained unchanged. The excitation-contraction coupling (ECC) gain function measured as Δ[Ca2+]i/ICa 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, ICa becomes less able to trigger ...