Reentry in survived subepicardium coupled to depolarized and inexcitable midmyocardium: insights into arrhythmogenesis in ischemia phase 1B.
BACKGROUND
Delayed ventricular arrhythmias during acute myocardial ischemia (1B arrhythmias) are associated with an increase in tissue impedance and are most likely sustained in a thin subepicardial layer.


OBJECTIVE
The goal of this study was to test the hypothesis that heterogeneous uncoupling between depolarized midmyocardium and surviving subepicardium results in heterogeneous refractoriness in the latter, providing the reentry substrate after a premature beat.


METHODS
A 3-dimensional bidomain slab was constructed comprising a normal subepicardial layer coupled to a slightly depolarized (-80 to -60 mV) but inexcitable midmyocardium. Experimentally measured tissue impedance served as input for the model. Four stages of heterogeneous uncoupling between the 2 layers were simulated, each corresponding to an experimental ischemic impedance value. Effective refractory periods (ERP), conduction velocities, and inducibility of reentry were examined.


RESULTS
Heterogeneous uncoupling resulted in subepicardial ERP dispersion, allowing reentry to occur. The minimum ERP dispersion needed to induce reentry was 28 ms. Reentry induction was only possible in this model at the 2 intermediate stages of uncoupling, and only when midmyocardial resting membrane potential was more negative than -60 mV. Complete uncoupling of the layers resulted in normal subepicardial conduction without arrhythmias. The minimum length of the reentrant pathway was 2.5 cm, comparable to 2.4 cm reported in previous experiments.


CONCLUSIONS
Heterogeneous uncoupling to a negative sink such as depressed inexcitable midmyocardium may be a substrate for ischemia 1B arrhythmias. Total uncoupling removes the arrhythmogenic substrate.
Jie
Xiao
X
Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, USA.
Rodríguez
Blanca
B
de Groot
Joris R
JR
Coronel
Ruben
R
Trayanova
Natalia
N
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D003198:Computer Simulation; D006321:Heart / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D009206:Myocardium; D010496:Pericardium / Q000503:physiopathology; D012032:Refractory Period, Electrophysiological