Cellular graded responses and ventricular vulnerability to reentry by a premature stimulus in isolated canine ventricle

Masamichi Gotoh, Takumi Uchida, William J. Mandel, Michael C. Fishbein, Peng Sheng Chen, Hrayr S. Karagueuzian

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Background: The cellular mechanism by which a point strong premature stimulus (S2) induces reentry is unknown. We hypothesized that cellular graded responses induced by an S2 mediate and control tissue vulnerability to reentry. Methods and Results: Reentry is induced in normal canine ventricular epicardial slices (30x38x2 mm, n=30) by an S2 at intervals shorter than the effective refractory period. The S1 is applied at the edge and the S2 at the center of the tissue. The line connecting the S1-S2 sites is parallel to the long axis of the fiber orientation. Isochronal activation maps were constructed with 56 to 480 bipolar electrodes, and the activation pattern was visualized dynamically. Reentry induced by an S2 is mediated by the graded responses as follows: The induced graded responses propagate with decrement toward recovered cells. When the amplitude of the propagated depolarizing graded responses reaches threshold relative to the recovering cells, an action potential is initiated along the fiber 2 to 3 mm away from the cathode of the S2. The distally initiated activation wave front blocks near the S2 site because the same S2-induced graded response prolongs the refractory period. The 'broken' wave front then circulates around both sides of the block and reenters when the site of block recovers its excitability, completing the first figure-eight reentry cycle. Reentry cannot be induced when the S2 strength is >72±21 mA (upper limit of vulnerability) because these strong S2-induced graded responses convert the unidirectional block to bidirectional block by excess prolongation of the refractoriness. Conclusions: We conclude that the magnitude and the propagation of S2-induced cellular graded responses mediate and control vulnerability to reentry in the ventricular epicardium.

Original languageEnglish (US)
Pages (from-to)2141-2154
Number of pages14
Issue number8
StatePublished - Apr 15 1997


  • anisotropy
  • depolarizing
  • fibrillation
  • reentry
  • ventricles

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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