Spatiotemporal heterogeneity in the induction of ventricular fibrillation by rapid pacing importance of cardiac restitution properties

The mechanism by which rapid pacing induces ventricular fibrillation (VF) i s unclear. We performed computerized epicardial mapping studies in 10 dogs, using 19-beat pacing trains. The pacing interval (PI) of the first train w as 300 ms and then was progressively shortened until VF was induced. For ea ch PI, we constructed restitution curves for the effective refractory perio d (ERP). When the PI was long, the activation cycle length (CL) was constan t throughout the mapped region. However, as the PI shortened, there was an increase in the spatiotemporal complexity of the CL variations and an incre ase 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. Com puter 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 i ntact. By altering CV and ERP restitutions in this model, we found that CV restitution creates spatial CL variations, whereas ERP restitution underlie s temporal, beat-to-beat variations in refractoriness during rapid pacing. Together, the interaction of CV and ERP restitutions produces spatiotempora l oscillations in cardiac activation that increase in amplitude as the PI d ecreases, ultimately causing wavebreak at the site of intrinsic heterogenei ty. 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 t he initiation of VF by rapid pacing.