Graded response and restitution hypotheses of ventricular vulnerability to fibrillation: Insights into the mechanism of initiation of fibrillation

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Abstract

According to the upper limit of vulnerability (ULV), failed defibrillation (DF) shocks reinitiate ventricular fibrillation (VF) by falling on the vulnerable period of one or more of the fibrillation wavefronts. The failed shock first induces reentry (stage I VF), which within few cycles degenerate to stage II VF. We developed 2 hypotheses of vulnerability that explain DF failure using isolated and intact in situ ventricles. Activation maps were constructed with high-resolution electrodes and action potential (AP) recorded with microelectrodes. According to the graded response (GR) hypothesis, reentry is formed when a critical shock strength induces a GR that transiently increases local refractoriness. The GR propagates and initiates distal regenerative activity that propagates around the site of block to reenter through it as it recovers. Ultrastrong shocks prevent reentry by converting unidirectional block to bidirectional block by excessive increase in refractoriness, a finding that supports the ULV hypothesis. In situ ventricle stimulus-induced termination of reentry and stage I VF (protective zone) could be explained by the GR hypothesis. The induced functional reentry with periods of 100 to 160 ms engages the steep (unstable) portion of the AP duration restitution curves (slope >1) that promotes meandering and breakup. This leads to transition from stage I to stage II VF (the restitution hypothesis). We conclude that the GR and restitution hypotheses provide an insight into the mechanism of ventricular vulnerability to fibrillation induced by a stimulus. These hypotheses provide a new paradigm for effective antifibrillatory strategies.

References (15)

  • CJ Wiggers et al.

    Studies of ventricular fibrillation caused by electric shock. II. Cinematographic and electrocardiographic observation of the natural process in the dog's heart

  • P-S Chen et al.

    Mechanism of ventricular vulnerability to single premature stimuli in open-chest dogs

    Circ Res

    (1988)
  • F Fenton et al.

    Vortex dynamics in three-dimensional continuous myocardium with fiber rotation: filament instability and fibrillation

    Chaos

    (1998)
  • A Karma

    Spiral breakup in model equations of action potential propagation in cardiac tissue

    Phys Rev Lett

    (1993)
  • JJ Lee et al.

    Reentrant wave fronts in Wiggers' stage II ventricular fibrillation: characteristics, and mechanisms of termination and spontaneous regeneration

    Circ Res

    (1996)
  • C Bonometti et al.

    Interaction between strong electrical stimulation and reentrant wavefronts in canine ventricular fibrillation

    Circ Res

    (1995)
  • T Ikeda et al.

    Meandering and Unstable reentrant wave fronts induced by acetylcholine in isolated canine right atrium

    Am J Physiol

    (1997)
There are more references available in the full text version of this article.

Supported in part by UC Tobacco Related Disease Research Program (6RT-0020), NIH SCOR grant (HL52319), the Cedars-Sinai ECHO Foundation, the Ralph M. Parsons Foundation, Los Angeles, CA, AHA National Center Grant-in-Aid 9750623N and 9956464N, and the Pauline and Harold Price Endowment.

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