Biphasic Restitution of Action Potential Duration and Complex Dynamics in Ventricular Myocardium

The purpose of this study was to determine whether biphasic restitution of action potential duration (APD) in ventricular muscle permits the development of complex dynamic behavior. Such behavior is expected because of the steep ascending slope of restitution and the presence of a maximum. Action potentials recorded from strips of epicardial muscle in which biphasic APD restitution occurred demonstrated a characteristic pattern of phase locking during progressive shortening of the pacing cycle length. 1:1 locking was replaced by irregular dynamics, which in turn was replaced by higher order periodic behavior (eg, 8:8 locking), then by 2:2 locking, and finally by 2:1 locking. Similar patterns of dynamic behavior were produced in a computer model by using a piecewise linear approximation of biphasic APD restitution. Features of APD restitution that were critical determinants of irregular dynamics included the slopes of the ascending and the nonmonotonic regions. These results suggest that rate-related alterations of APD and refractoriness may be affected significantly by small nonmonotonicities in APD restitution.