Spatiotemporal Heterogeneity in the Induction of Ventricular Fibrillation by Rapid Pacing

Abstract

The mechanism by which rapid pacing induces ventricular fibrillation (VF) is unclear. We performed computerized epicardial mapping studies in 10 dogs, using 19-beat pacing trains. The pacing interval (PI) of the first train was 300 ms and then was progressively shortened until VF was induced. For each PI, we constructed restitution curves for the effective refractory period (ERP). When the PI was long, the activation cycle length (CL) was constant throughout the mapped region. However, as the PI shortened, there was an increase in the spatiotemporal complexity of the CL variations and an increase in the slope of the ERP restitution curve. In 5 dogs, we documented the initiation of VF by wavebreak at the site of long-short CL variations. Computer simulation studies using the Luo-Rudy I ventricular action potential model in simulated 2-dimensional tissue reproduced the experimental results when normal ERP and conduction velocity (CV) restitution properties were intact. By altering CV and ERP restitutions in this model, we found that CV restitution creates spatial CL variations, whereas ERP restitution underlies temporal, beat-to-beat variations in refractoriness during rapid pacing. Together, the interaction of CV and ERP restitutions produces spatiotemporal oscillations in cardiac activation that increase in amplitude as the PI decreases, ultimately causing wavebreak at the site of intrinsic heterogeneity. This initial wavebreak then leads to the formation of spiral waves and VF. These findings support a key role for both CV and ERP restitutions in the initiation of VF by rapid pacing.

Mechanisms for Discordant Alternans

“…However, at the high pacing rates at which discordant alternans is seen, DI typically is small, and effects of conduction velocity cannot be separated from effects of repolarization. In contrast, in a recent study 33 of the induction of ventricular brillation by rapid pacing in the dog and Luo-Rudy I ionic model, it was concluded that conduction velocity was important for producing spatial inhomogeneities of CL and DI. The results of our simulations show that both the sinus node and ectopic focus scenarios are valid ways of initiating discordant alternans in homogeneous tissue, and that conduction velocity restitution is crucial in the former, but not necessary in the latter.…”

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

“…To create a local gradient of [K ϩ ]o, the left marginal vein was cannulated with a custom-made polyethylene catheter and perfused separately with Tyrode's solution containing K ϩ concentrations of 4,6,8,10, and 12 mM. The concentration of Na ϩ was decreased proportionally to maintain constant osmolarity.…”

“…We conclude that spatial heterogeneity of the APD restitution, created with regional elevation of [K ϩ ]o, can lead to AP instability, 2:1 block, and reentry induction. restitution heterogeneity; regional perfusion; optical mapping THE STATIONARY AND DYNAMIC heterogeneities of electrophysiological properties of cardiac tissue play a key role in the induction and maintenance of cardiac arrhythmias (1,10,16,59). Cardiac tissue heterogeneities increase drastically when acute regional ischemia occurs.…”

A Tale of Two Fibrillations

“…Whereas steep APD restitution drives wave instability by making the waveback sensitive to small changes in diastolic interval, CV can drive wave instability by making the wavefront sensitive to small changes in diastolic interval, especially if structural and electrophysiological heterogeneities are present. Computer simulations 29 showed that without CV restitution, CV is essentially constant throughout the tissue during rapid pacing. Therefore, the arrival time of an impulse at a given distance from the pacing site has no way to vary between successive beats, assuming no change of the conduction pathway.…”