Cellular mechanism of reentry induced by a strong electrical stimulus: Implications for fibrillation and defibrillation

Hrayr S. Karagueuzian, Peng Sheng Chen

Research output: Contribution to journalReview articlepeer-review

30 Scopus citations


The objective of this review article is to describe the graded response hypothesis of reentry induced by a strong single electrical stimulus in the normal canine ventricular myocardium. It is shown that the graded responses (subthreshold depolarization during phase 3 of the action potential) induced at a site distant (S2) from the regular S1-S1 pacing site, propagate slowly over short distances (∼5 mm) and initiate a regenerative action potentials in recovered cells near the S1 site. Activation wave then blocks near the S2 site (unidirectional block) but reenters when the S2 site recovers it excitability. Super strong S2 currents do not induce reentry (upper limit of vulnerability). Since similar activation sequence and properties are shown to exist in intact canine hearts during induction of ventricular fibrillation with a similar S2 stimulus, the graded response hypothesis may have relevance to vulnerability to fibrillation. Furthermore, since the upper limit of vulnerability is closely related to defibrillation threshold, the graded response hypothesis might also be relevant to defibrillation mechanism. Other proposed mechanisms of fibrillation and defibrillation (critical point hypothesis, the progressive depolarization hypothesis and the hypothesis of phase singularity of defibrillation failure) are also discussed in this review paper and compared to the graded response hypothesis.

Original languageEnglish (US)
Pages (from-to)251-262
Number of pages12
JournalCardiovascular research
Issue number2
StatePublished - 2001


  • Arrhythmia (mechanisms)
  • Defibrillation
  • Sudden death
  • Ventricular arrhythmias

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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