Restitution of Action Potential Duration During Oscillatory Changes in Diastolic Intervals in the Swine Myocardium

Abstract

Cardiac electrical restitution is thought to importantly influence whether an electrical disturbance degenerates into a reentrant activation. We quantified restitution relationship using a previously developed feedback-based protocol that permits explicit control of diastolic intervals (DIs) that can be changed sequentially in time. An oscillatory DI sequence was used to quantify dependence of APDs on previous activation history. In four swine, endocardial tissue from the free wall of right ventricle was excised and superfused using Tyrodes solution . Pacing stimuli of 3 ms duration were delivered through a bipolar platinum-iridium electrode. Transmembrane potentials were recorded using glass microelectrodes filled with 3 mol KCl while the DIs changed in an oscillatory pattern. The APD vs DI relationship, i.e. restitution, showed a bimodal trajectory similar to hysterisis. The APD’s during increasing phase of DI were smaller than the APDs during decreasing phase of DI. We consider that the hysteresis in restitution shows direct evidence of the effects of memory on APD. The observation that the trajectories of APDs are different during increasing and decreasing phases of DI suggest that the role of restitution in activation instability is likely more complex than what is currently considered.