Interdependence of modulated dispersion and tissue structure in the mechanism of unidirectional block

We previously showed that a premature stimulus can significantly alter vuln erability to arrhythmias by modulating spatial gradients of ventricular rep olarization (ie, modulated dispersion). However, it is not clear if such ch anges in arrhythmia vulnerability can be attributed to the formation of an electrophysiological substrate for unidirectional block and what the potent ial role is of tissue structure in this process. Therefore, the main object ive of the present study was to examine the concomitant effect repolarizati on gradients and tissue structure have on unidirectional block. Optical act ion potentials were recorded from 128 ventricular sites (1 cm(2)) in 8 Lang endorff-perfused guinea pig hearts. Propagation was confined to the epicard ial surface using an endocardial cryoablation procedure, and a 12-mm barrie r with a 1.5-mm isthmus was etched with a laser onto the epicardium. A prem ature stimulus (S2) was delivered over a range of S1S2 coupling intervals t o modulate repolarization gradients in a predictable fashion. When a second premature stimulus (S3) was delivered from the center of the isthmus, the occurrence and orientation of unidirectional block were highly dependent on repolarization gradients created by the S2 beat. In this model, a local re polarization gradient of 3.2 ms/mm was required for unidirectional block at this isthmus, In addition, the formation of unidirectional block was criti cally dependent on the presence of the source-sink mismatch imposed by the isthmus. These results may explain how the interplay between spatial hetero geneities of repolarization and tissue structure form a substrate for unidi rectional block and reentry.