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

Abstract

Background The cellular mechanism by which a point strong premature stimulus (S 2 ) induces reentry is unknown. We hypothesized that cellular graded responses induced by an S 2 mediate and control tissue vulnerability to reentry. Methods and Results Reentry is induced in normal canine ventricular epicardial slices (30×38×2 mm, n=30) by an S 2 at intervals shorter than the effective refractory period. The S 1 is applied at the edge and the S 2 at the center of the tissue. The line connecting the S 1 -S 2 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 S 2 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 S 2 . The distally initiated activation wave front blocks near the S 2 site because the same S 2 -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 S 2 strength is >72±21 mA (upper limit of vulnerability) because these strong S 2 -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 S 2 -induced cellular graded responses mediate and control vulnerability to reentry in the ventricular epicardium.