d,l-Sotalol at therapeutic concentrations facilitates the occurrence of long-lasting non-stationary reentry during ventricular fibrillation in isolated rabbit hearts

Yu-Cheng Hsieh, Tzyy-Leng Horng, Shien-Fong Lin, Tung-Chao Lin, Chih-Tai Ting, Tsu-Juey Wu
Circulation Journal: Official Journal of the Japanese Circulation Society 2009, 73 (1): 39-47

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.

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