Analysis of Damped Oscillations during Reentry: A New Approach to Evaluate Cardiac Restitution

Abstract

Reentry is a mechanism underlying numerous cardiac arrhythmias. During reentry, head-tail interactions of the action potential can cause cycle length (CL) oscillations and affect the stability of reentry. We developed a method based on a difference-delay equation to determine the slopes of the action potential duration and conduction velocity restitution functions, known to be major determinants of reentrant arrhythmogenesis, from the spatial period P and the decay length D of damped CL oscillations. Using this approach, we analyzed CL oscillations after the induction of reentry and the resetting of reentry with electrical stimuli in rings of cultured neonatal rat ventricular myocytes grown on microelectrode arrays and in corresponding simulations with the Luo-Rudy model. In the experiments, P was larger and D was smaller after resetting impulses compared to the induction of reentry, indicating that reentry became more stable. Both restitution slopes were smaller. Consistent with the experimental findings, resetting of simulated reentry caused oscillations with gradually increasing P, decreasing D, and decreasing restitution slopes. However, these parameters remained constant when ion concentrations were clamped, revealing that intracellular ion accumulation stabilizes reentry. Thus, the analysis of CL oscillations during reentry opens new perspectives to gain quantitative insight into action potential restitution.