Within the LV free wall, there is substantial spatial heterogeneity. Low flow (LF) areas (300 ml, <60% of mean flow) display low energy turnover and demand and also a 3-fold higher expression of ERG and KChIP2, encoding the IKr-a-subunit and modulating Ito. Since these currents shorten action potential duration (APD), we tested whether a) locally enhanced ERG causes a spatial APD pattern, b) ERG blockade modulates energy demand, and c) short local APD correlates with LF and high ERG expression.

In the open-chest canine heart, epicardial mapping of activation-repolarization intervals corrected for heart rate variations (ARIc) revealed an apico-basal gradient as well as a spatial pattern (CV 3,8%). The shortest and longest ARIc differed by 69±17 ms (n=11). Blocking ERG by dofetilide increased ARIc much more effectively in short than in long ARIc areas (18±5 vs. 7±5%, n=9). However, it only mildly increased perfusion and energy demand in LF areas (n=7). In addition, biopsies from short ARIc areas demonstrated a 3-fold higher ERG expression and a lower flow (p < 0,05, n=4).

Thus the spatial pattern of perfusion predicts the extent of local K⁺ channel expression and APD, and vice versa. An enhanced dispersion of APD, e.g. following left bundle branch block, may subsequently contribute to life-threatening arrhythmias.