Slow and long-lasting modulation of myocardial repolarization produced by ectopic activation in isolated rabbit hearts: evidence for cardiac memory

Prolonged ventricular pacing induces T wave polarity changes that persist long after cessation of pacing. To examine how ventricular repolarization is modulated by prolonged changes in activation sequence, we studied the effect of ectopic pacing on the distribution of action potential durations (APDs) in nine isolated Langendorff-perfused rabbit hearts. A contact electrode probe was used to map right and left ventricular-epicardial monophasic action potentials during three consecutive changes in stimulus site, that is, 1) during 45 minutes of right atrial pacing, 2) during 120 minutes of right ventricular pacing, and 3) again, during 60 minutes of right atrial pacing. During each of these phases, the effect of activation sequence on repolarization was examined by linear-regression analysis of APD on activation time (AT). Results averaged for all nine hearts showed that during the initial atrial-pacing phase, APD was inversely related to AT (slope [S] = -1.63; r = 0.76), indicating that sites with earlier activation repolarized later. With the onset of ventricular pacing, the inverse correlation between AT and APD disappeared (S = -0.19; r = 0.31). Continuing ventricular pacing, however, produced slow changes in APD that restored the inverse relation (S = -0.71; r = 0.68 at 120 minutes; p less than 0.0002 versus 5 minutes). Switching from ventricular to atrial pacing again perturbed the inverse correlation (S = 0.28; r = 0.35) but at 60 minutes of atrial pacing, a significant inverse correlation was reestablished (S = -1.25; r = 0.53; p less than 0.01 versus 5 minutes). An inverse correlation between AT and APD tends to synchronize repolarization time (RT, the sum of AT and APD).