Data deposition for Complex electrophysiological remodeling in postinfarction ischemic heart failure

Heart failure (HF) following myocardial infarction (MI) is associated with
high incidence of cardiac arrhythmias. Development of therapeutic strategy
requires detailed understanding of electrophysiological remodeling.
However, changes of ionic currents in ischemic HF remain incompletely
understood, especially in translational large animal models. Here, we
systematically measure the major ionic currents in ventricular myocytes
from the infarct border and remote zones in a porcine model of post-MI HF.
We recorded eight ionic currents during the cell’s action potential (AP)
under physiologically relevant conditions using selfAP-clamp Sequential
Dissection. Compared to healthy controls, HF-remote zone myocytes
exhibited increased late Na+ current, Ca2+-activated K+ current,
Ca2+-activated Cl- current, decreased rapid delayed rectifier K+ current,
and altered Na+/Ca2+ exchange current profile. In HF-border zone myocytes,
the above changes also occurred but with additional decrease of L-type
Ca2+ current, decrease of inward rectifier K+ current, and Ca2+
release-dependent delayed afterdepolarizations. Our data reveal that the
changes in any individual current are relatively small, but the integrated
impacts shift the balance between the inward and outward currents to
shorten AP in the border zone but prolong AP in the remote zone. This
differential remodeling in post-MI HF increases the inhomogeneity of AP
repolarization which may enhance the arrhythmogenic substrate. Our
comprehensive findings provide a new mechanistic framework for
understanding why single channel blockers may fail to suppress
arrhythmias, and highlight the need to consider the rich tableau and
integration of many ionic currents in designing therapeutic strategies for
treating arrhythmias in HF.