Transmural action potential changes underlying ventricular electrical remodeling.

Abstract

Although it is well established that alterations in heart rate or activation sequence induce electrical remodeling in the atria, electrical remodeling in the ventricle is poorly understood. To determine the changes in cellular repolarization that underlie ventricular electrical remodeling caused separately by altered heart rate and activation sequence, optical action potentials were recorded simultaneously from 256 sites spanning the transmural wall of the arterially perfused canine wedge preparation (n = 15). Action potentials were compared from the same sites under identical conditions [endocardial pacing, cycle length (CL) = 1,000 msec], before and after an intervening 20- to 60-minute period of remodeling induced by (1) rapid pacing (CL = 300 msec) with no change in activation sequence; (2) altered activation sequence (epicardial pacing) with no change in rate; or (3) no change in rate or activation sequence (control). Action potential duration (APD) shortened by 24.8 +/- 4.8 msec following a period of rapid heart rate (P < 0.05) but prolonged (by 12.7 +/- 1.8 msec) following a period of altered activation sequence (P < 0.05). Hence, even after restoration of baseline heart rate and activation sequence, there were persistent changes in APD from baseline, indicative of electrical remodeling. Moreover, the orientation of the maximum APD gradient across the transmural wall changed more significantly following heart rate remodeling (by 27.7 degrees +/- 4.9 degrees, P < 0.05) than following activation sequence remodeling (by 12.3 degrees +/- 2.4 degrees, P < 0.05). Persistent changes in ventricular repolarization can be induced by surprisingly short periods of altered rate or activation sequence. In contrast to atrial remodeling, electrical remodeling in the ventricle can result in prolonged APD (with altered activation sequence) or reversal of APD gradient orientation (with rapid rate), suggesting that the nature of ventricular electrical remodeling induced by these two perturbations is different.