| Intrinsic electrophysiological heterogeneity and the anisotropic muscular architecture of the ventricle conspire to form a substrate for cardiac arrhythmias. Using a computer model, we studied how these factors influence the activation and recovery processes of paced beats in the ventricle.; A section of the canine left ventricle was modeled as a three-dimensional bidomain adjoined by a blood cavity. Fenton-Karma membrane kinetics were varied transmurally to approximate the action potential duration (APD) profile observed in isolated wedges of left ventricular tissue. With uniform membrane properties, normal and premature simulated beats propagated smoothly through the tissue. However, rotational anisotropy and tissue boundaries gave rise to a complex pattern of APD caused by the misalignment of activation and recovery sequences. While the presence of intramural ionic heterogeneity did not affect the conduction of a normal epicardial beat, it establish a refractory wake that caused the subsequent premature beat to block in the midwall. Increasing electrotonic coupling across the wall reduced both APD dispersion and the extent of conduction block encountered by the premature wavefront. Although the transmural APD profile was nearly identical between epicardial and endocardial pacing, premature beats from the endocardium were not prone to block. Thus, our model shows that (1) electrophysiological heterogeneity contributes to conduction block by increasing the dispersion of refractoriness, (2) increased APD dispersion alone is an insufficient marker of functional block, and (3) decreased transmural conductivity acts to promote arrhythmia by increasing transmural APD gradients and thus the likelihood of conduction block.; To test the predictions of our computer model, we pace-mapped the canine left ventricle using 528 unipolar electrograms (UEGs) recorded simultaneously from epicardial and transmural sites. Maps of conduction velocity and activation-recovery interval (ARI) revealed (1) a tripolar pattern of ARI during normals beats that vanished in the premature beat, (2) reduced intramural conduction velocity during premature beats however, though block was not observed, and (3) while intramural ARI was longest in the midwall however, the profile was inverted following the early beat as expected from the enhanced sensitivity to diastolic interval displayed by M-cells. |
