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(Circulation. 1997;95:2141-2154.)
© 1997 American Heart Association, Inc.

Articles

Cellular Graded Responses and Ventricular Vulnerability to Reentry by a Premature Stimulus in Isolated Canine Ventricle

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

From the Division of Cardiology, Department of Medicine, and the Division of Anatomic Pathology (M.C.F.), Department of Pathology, Burns and Allen Research Institute, Cedars-Sinai Medical Center and the University of California, Los Angeles. Dr Gotoh's present address is Nippon Medical School, Tokyo, Japan.

Correspondence to Hrayr S. Karagueuzian, PhD, Cedars-Sinai Research Institute, Davis Research Bldg, Room 6066, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail karagueuzian{at}.csmc.edu

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.

Key Words: depolarizing • anisotropy • fibrillation • reentry • ventricles

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