Complex electrophysiological remodeling in postinfarction ischemic heart failure

著者: Bence Hegyi, Julie Bossuyt, Leigh G. Griffiths, Rafael Shimkunas, Zana Coulibaly, Zhong Jian, Kristin Grimsrud, Claus S. Søndergaard, Kenneth S. Ginsburg, Nipavan Chiamvimonvat, Luiz Belardinelli, András Varró, Julius Gy. Papp, Piero Pollesello, Jouko Levijoki, Leighton T. Izu, W. Douglas Boyd, Tamás Bányász, Donald M. Bers, Ye Chen‐Izu - Proceedings of the National Academy of Sciences, PNAS 2018 被引用: 101

release-dependent delayed after-depolarizations. 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 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.