Post-repolarization refractoriness increases vulnerability to block and initiation of reentrant impulses in...

Myocardial infarction causes remodeling of the tissue structure and the density and kinetics of several ion channels in the cell membrane. Heterogeneities in refractory period (ERP) have been shown to occur in the infarct border zone and have been proposed to lead to initiation of arrhythmias. The purpose of this study is to quantify the window of vulnerability (WV) to block and initiation of reentrant impulses in myocardium with ERP heterogeneities using computer simulations. We found that ERP transitions at the border between normal ventricular cells (NZ) with different ERPs are smooth, whereas ERP transitions between NZ and infarct border zone cells (IZ) are abrupt. The profile of the ERP transitions is a combination of electrotonic interaction between NZ and IZ cells and the characteristic post-repolarization refractoriness (PRR) of IZ cells. ERP heterogeneities between NZ and IZ cells are more vulnerable to block and initiation of reentrant impulses than ERP heterogeneities between NZ cells. The relationship between coupling intervals of premature impulses (V1V2) and coupling intervals between premature and first reentrant impulses (V2T1) at NZ/NZ and NZ/IZ borders is inverse (i.e. the longer the coupling intervals of premature impulses the shorter the coupling interval between the premature and first reentrant impulses); this is in contrast with the reported V1V2/V2T1 relationship measured during initiation of reentrant impulses in canine infarcted hearts which is direct.

(1) ERP transitions at the NZ-IZ border are abrupt as a consequence of PRR; (2) PRR increases the vulnerability to block and initiation of reentrant impulses in heterogeneous myocardium; (3) V1V2/V2T1 relationships measured at ERP heterogeneities in the computer model and in experimental canine infarcts are not consistent. Therefore, it is likely that other mechanisms like micro and/or macro structural heterogeneities also contribute to initiation of reentrant impulses in infarcted hearts.