Electrotonic effects on action potential duration in perfused rat hearts

Electrotonic interactions in cardiac tissue have been shown previously to modulate dynamical properties of the myocardium such as action potential duration (APD) and action potential duration restitution. A recent computational study indicated that these electrotonic effects may be strongest in small murine hearts. In the present study, we investigate experimentally how APD is modulated by activation sequence and pacing rate using optical mapping in Langendorff perfused rat hearts. Our results show that following an epicardial point stimulus, a strong correlation exists between epicardial APD and activation time, with decreasing APD for increasing activation time. This effect is preserved for all pacing frequencies (6-14 Hz) investigated in this study. Our experimental results are validated by detailed three-dimensional computer simulations. These simulations also demonstrate a strong transmural APD dependence on activation sequence, which, near the pacing site, is sufficient to mask the intrinsic transmural gradient.