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.

Alternans Resonance and Propagation Block during Supernormal Conduction in Cardiac Tissue with Decreased [K+]o

“…Conduction in cardiac fibers (length: 1 or 10 cm) was simulated using the LR-I model (22). As done previously (7,8,24), the maximum sodium current conductance and the slow inward current conductance were reduced to 8 and 0.04 mS/cm 2 , respectively. Tissue conductivity (lumped intracellular, extracellular, and junctional: 3.333 mS/cm) normalized by the surface/volume ratio (3636 cm À1 ) was 0.9167 mS, giving a control CV in the range of 40 cm/s.…”

“…Past studies demonstrate that not only APD restitution but also CV restitution determines the stability of conduction and arrhythmogenesis (5)(6)(7). The conjunction of both APD and CV restitution also governs the dynamics of head-tail AP interactions during reentry (8), the occurrence of conduction block during rapid pacing (9)(10)(11)(12), and the generation of spatially discordant alternans (13)(14)(15).…”

New drugs vs. old concepts: A fresh look at antiarrhythmics

“…Complex mechanisms take part in the genesis of arrhythmias. Reentry can lead to ion accumulation (in particular Na + and Ca 2+ ) (Munteanu et al, 2008) and, conversely, high intracellular Ca 2+ can initiate cardiac remodeling that creates a substrate for reentry. AP prolongation can initiate early afterdepolarisations (EADs), and aberrant spontaneous diastolic Ca 2+ release via leaky RyR2 activates I ti (through NCX) to trigger DAD and, subsequently, VA (typically in HF and CPVT).…”

The Transfer Functions of Cardiac Tissue during Stochastic Pacing

“…Simulations of conduction were conducted in a 1-cm-long fiber of 100 Luo-Rudy phase 1 model cells (19). To obtain CVs and APDs in the range of those observed in cultures of neonatal rat ventricular myocytes, the maximum sodium current conductance (g Na ) and the slow inward current conductance (g si ) were reduced to 8 and 0.04 mS/cm 2 , respectively, as done in previous studies (1,23). The fiber was discretized at the level corresponding to the size of a cell (100 mm) and the lumped myoplasmic and gap junctional intercellular conductance was set to 1.267 mS, as previously published (23,24).…”