Elfects of activation sequence and anisotropic cellular geometry on the repolarization phase of action potential of dog ventricular muscles

The influence of activation sequences on action potential configuration, especially in the repolarization phase, was examined in isolated canine ventricular muscles. Action potentials were recorded from the epicardial surface in the center of a preparation having nearly uniform fiber orientation (25 x 25 mm). Stimuli applied just adjacent to the recording site produced nearly centrifugal propagation. An activation sequence either parallel (longitudinal) or perpendicular (transverse) to the long axis of the muscle fibers was produced by peripheral stimulation. Action potential duration at 60 mV (APD 60mv) during centrifugal propagation was significantly longer than that during longitudinal propagation. Further shortening of APD 6omV was observed during transverse propagation. When a collision of longitudinal or transverse wavefronts (longitudinal or transverse collision) was produced at the action potential recording site, the shortest APD was recorded. During centrifugal propagation, action potential mapping around the stimulating electrodes revealed that APD 60mV shortened gradually as the recording site was moved further from the stimulation site. The spatial gradient of APD was steeper in the transverse than in the longitudinal direction, causing a distortion in the repolarization sequence and the recovery of excitability near the center of the tissue. Premature stimuli applied to an area near the central stimulation site induced one-way block and circus movement of the wavefront, indicating reentry of excitation. We concluded that the activation sequence and anisotropic cellular geometry substantially affect APD, and that such a change contributes to the spatial inhomogeneity of refractoriness leading to reentrant arrhythmias. Circulation 76, No. 1, 226-236, 1987. THE PROPAGATION of excitation in cardiac muscle has generally been treated as though it occurred in a continuous structure. According to the continuous-medium theory, the time courses of transmembrane action potentials in cardiac tissue with homogenous membrane properties should be the same everywhere when the resting or take-off potential is the same. Contrary to this prediction, recent experiments by Spach et al.` demonstrated that the rate of rise of action potentials in atrial or ventricular muscles was greatly affected by the activation sequence. They explained these facts by assuming an electrotonic interaction between neighboring cells in tissue having anisotropic cellular geomFrom the Department of Circulation and Respiration, The Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. Address for correspondence: Toshiyuki Osaka, M. D., Department of Circulation and Respiration, The Research Institute of Environmental Medicine, Nagoya University, Furo-Cho, Chikusa-ku, Nagoya, Japan. Received Dec. 10. 1986; revision accepted March 13, 1987. etry, and proposed a concept of "discontinuous conduction." If the repolarization phase of an action potential were affected by similar electrotonic interaction during the propagation of excitation, a substantial change in action potential duration (APD) and refractoriness would be induced. However, little information is available on this issue.6'-" In the present study the effects of activation sequence on action potential configuration, especially in the repolarization phase, were examined in isolated canine ventricular muscle preparations. The influence of the resultant change in APD on the recovery of excitability from region to region was also investigated to evaluate possible roles for the genesis of reentrant arrhythmias.