d,l-Sotalol at Therapeutic Concentrations Facilitates the Occurrence of Long-lasting Non-stationary Reentry During Ventricular Fibrillation in Isolated Rabbit Hearts

Abstract

Background: The effects of d,l-sotalol at therapeutic concentrations (<or=10 mg/L) on wavefront dynamics during ventricular fibrillation (VF) and electrophysiological heterogeneity remain unclear. Methods and results: By using an optical mapping system, epicardial activation patterns of VF were studied in 6 Langendorff-perfused rabbit hearts at baseline, during 10 mg/L d,l-sotalol infusion, and after washout. In an additional 4 hearts, action potential duration (APD), conduction velocity, and wavelength (WL) restitutions were determined. During d,l-sotalol infusion, VF was terminated in 3 of the 6 hearts. Only 1 heart developed transient ventricular tachycardia (VT). d,l-Sotalol reduced the number of phase singularities (ie, wavebreak) during VF (P<0.05), and it also increased the occurrence frequency (P<0.05) and lifespan (P<0.05) of epicardial reentry during VF. These reentries were non-stationary in nature and did not anchor on anatomical structures. Restitution data showed that d,l-sotalol flattened APD restitution. Furthermore, APD dispersion and spatial heterogeneity of restitutions were not enhanced by d,l-sotalol. Conclusions: d,l-Sotalol at therapeutic concentrations decreased wavebreak and facilitated the occurrence of long-lasting, non-stationary reentry during VF. However, VT rarely occurred. The related mechanisms include: (1) flattening of APD restitution without enhancement of spatial heterogeneity of electrophysiological properties, causing wavefront organization, and (2) WL prolongation, preventing steady anchoring of reentry.