Chronic rapid atrial pacing (RAP) leads to changes that perpetuate atrial fibrillation (AF). Chronic atrial dilatation due to mitral regurgitation (MR) also increases AF inducibility, but it is not clear whether the underlying mechanism is similar. Therefore, we have investigated atrial electrophysiology in a canine MR model (mitral valve avulsion, 1 mo) using high-resolution optical mapping and compared it with control dogs and with the canine RAP model (6 -8 wk of atrial pacing at 600 beats/min, atrioventricular block, and ventricular pacing at 100 beats/min). At followup, optical action potentials were recorded using a 16 ϫ 16 photodiode array from 2 ϫ 2-cm left atrial (LA) and right atrial (RA) areas in perfused preparations, with pacing electrodes around the field of view to study direction dependency of conduction. Action potential duration at 80% repolarization (APD 80) was not different between control and MR but was reduced in RAP atria. Conduction velocities during normal pacing were not different between groups. However, the MR LA showed increased conduction heterogeneity during pacing at short cycle lengths and during premature extrastimuli, which frequently caused pronounced regional conduction slowing. Conduction in the MR LA during extrastimulation also displayed a marked dependence on propagation direction. These phenomena were not observed in the MR RA and in control and RAP atria. Thus both models form distinctly different AF substrates; in RAP dogs, the decrease in APD80 may stabilize reentry. In MR dogs, regional LA conduction slowing and increased directional dependency, allowing unidirectional conduction block and preferential paths of conduction, may account for increased AF inducibility. atrial conduction; optical mapping ATRIAL FIBRILLATION (AF) is a frequently occurring arrhythmia, present in ϳ5% of people over 65 yr old (5). Among the risk factors predisposing to AF are congestive heart failure (CHF), hypertension, and mitral valve disease, including both stenosis and insufficiency (reviewed in Ref. 5). In general, atrial dilatation is associated with an increased occurrence of AF (17,28).Prevailing theory suggests that inducibility of sustained AF requires either a shortening of refractoriness, increased dispersion of refractoriness, or conduction slowing (1). Other factors that have been implicated in the stabilization of AF include increased conduction heterogeneity and anisotropy (23). The presence of one or more of these proarrhythmic factors would thus represent a "substrate for AF," contributing to increased AF stability. Various animal models of AF have been developed to study AF substrate. Parasympathetic stimulation (either with direct vagal nerve stimulation or circulating cholinergic agents) results in shortening of atrial refractoriness and sustained AF (10, 16). Prolonged rapid atrial pacing (RAP) leads to shortening of refractoriness and sustained AF (18,30). In a dog model of CHF due to rapid ventricular pacing, no changes in refractoriness were found, but increased con...