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

Ji Min Cao, Zhilin Qu, Young Hoon Kim, Tsu Juey Wu, Alan Garfinkel, James N. Weiss, Hrayr S. Karagueuzian, Peng Sheng Chen

Research output: Contribution to journalArticle

190 Scopus citations


The mechanism by which rapid pacini; 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.

Original languageEnglish (US)
Pages (from-to)1318-1331
Number of pages14
JournalCirculation research
Issue number11
StatePublished - Jun 11 1999
Externally publishedYes



  • Anatomical obstacles
  • Bifurcation
  • Chaos
  • Restitution curve
  • Wavebreak

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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