Acceleration of functional reentry by rapid pacing in anisotropic cardiac monolayers: Formation of multi-wave functional reentries

Objective: Attempts to cardiovert tachycardia by rapid point pacing can sometimes result in transient or stable increase of the heart rate (acceleration), changed ECG morphology, and/or fibrillation. The goal of this study was to investigate the effect of rapid pacing on the dynamics of functional reentry in monolayer cultures of cardiac cells. Methods: Fully confluent, uniformly anisotropic monolayers of neonatal rat ventricular myocytes were prepared using methods of microabrasion. Cells were paced by a point electrode at rest and during functional reentry, and membrane voltages were optically mapped. Results: Point pacing readily induced single loop anisotropic functional reentry with monomorphic optical pseudo-ECG (pECG) and average rotation period of 193 ± 52 ms (n = 71 monolayers). Attempts to cardiovert reentry by rapid pacing at rates 10-50% faster than the reentry rate were successful in 57/71 monolayers. In 14/71 monolayers, the number of rotating waves was stably increased by 1 to 4, yielding a 10-70% acceleration of pECG rate and change to a different monomorphic or polymorphic pECG. The resulting multi-wave functional reentries were classified based on the number and direction of their rotating waves. The higher the number of waves in the multi-wave reentry, the more accelerated was the rate of cell firing in the monolayer. Importantly, stable acceleration was only inducible in monolayers with relatively deep and broad conduction velocity restitution relationships. Reapplication of point pacing further accelerated, decelerated, or eventually terminated the reentrant activity. Conclusions: These results suggest that stable multiplication of rotating waves in conjunction with a deep and broad conduction velocity restitution relationship is a possible mechanism for stable acceleration of functional reentry by rapid pacing.