Sudden cardiac death is the leading cause of death in the industrialized world, with the majority of such tragedies being due to ventricular fibrillation. Ventricular fibrillation is a frenzied and irregular disturbance of the heart rhythm that quickly renders the heart incapable of sustaining life. Rotors, electrophysiological structures that emit rotating spiral waves, occur in several systems that all share with the heart the functional properties of excitability and refractoriness. These re-entrant waves, seen in numerical solutions of simplified models of cardiac tissue, may occur during ventricular tachycardias. It has been difficult to detect such forms of re-entry in fibrillating mammalian ventricles. Here we show that, in isolated perfused dog hearts, high spatial and temporal resolution mapping of optical transmembrane potentials can easily detect transiently erupting rotors during the early phase of ventricular fibrillation. This activity is characterized by a relatively high spatiotemporal cross-correlation. During this early fibrillatory interval, frequent wavefront collisions and wavebreak generation are also dominant features. Interestingly, this spatiotemporal pattern undergoes an evolution to a less highly spatially correlated mechanism that lacks the epicardial manifestations of rotors despite continued myocardial perfusion.

Abstract-Classical concepts of atrial fibrillation (AF) have been rooted in Moe's multiple-wavelet hypothesis and simple cellular-automaton computer model. Recent experimental work has raised questions about the multiple-wavelet mechanism, suggesting a discrete "driver region" underlying AF. We reexplored the theoretical basis for AF with a 2-dimensional computer model of a 5ϫ10-cm sheet of atrial cells with realistic ionic and coupling properties. Vagal actions were formulated based on patch-clamp studies of acetylcholine (ACh) effects. In control, a single extrastimulus resulted in a highly meandering unstable spiral wave. Simulated electrograms showed fibrillatory activity, with a dominant frequency (DF, 6.5 Hz) that correlated with the mean rate. Uniform ACh reduced core meander of the spiral wave by Ϸ70% (as measured by the standard deviation of spiral-wave tip position) and accelerated the DF to 17.0 Hz. Simulated vagally induced refractoriness heterogeneity caused wavefront breakup as accelerated reentrant activity in regions of short refractoriness impinged on regions unable to respond in a 1:1 fashion because of longer refractoriness. In 7 simulations spanning the range of conditions giving sustained AF, 5 were maintained by single dominant spiral waves. On average, 3.0Ϯ1.3 wavelets were present (range, 1 to 7). Most wavelets were short-lived and did not contribute to AF maintenance. In contrast to predictions of the multiple-wavelet hypothesis, but in agreement with recent experimental evidence, our model indicates that AF can result from relatively stable primary spiral-wave generators and is significantly organized. Our results suggest that vagal AF may arise from ACh-induced stabilization of the primary spiral-wave generator and disorganization of the heterogeneous tissue response.