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.

Figure 1

A, effect of 10 mg/L d,l-sotalol on VF/VT transition and VF termination with respect to elapsed time in all 6 hearts of protocol I. B, effect of 10 mg/L d,l-sotalol on the mean DF of pseudo-ECG in protocol I. “n” indicates the number of hearts studied.

Figure 2

An example showing effects of d,l-sotalol on pseudo-ECG and DF in VF (data from heart #1). A through E, pseudo-ECG of VF at baseline (A), 10 mg/L d,l-sotalol infusion (B), VF termination (C), VF inducibility test (D), and washout period (E). A′ to E′, DF for corresponding pseudo-ECG tracings in A through E. See text for details.

Figure 3

Effects of d,l-sotalol on wavefront characteristics during different time points of VF in protocol I. A, average number of PSs in each phase map. B, runs of epicardial reentry observed in each recording time window. C, life span (in rotations) of epicardial reentry. D, percentage of recording time containing at least one epicardial reentry. “n” indicates the number of hearts studied. “Rs” indicates runs of reentry analyzed. See text for details.

Figure 4

Examples of non-stationary reentry during VF with 10 mg/L d,l-sotalol infusion. A through C, a drifting reentry recorded 7 minutes after the onset of d,l-sotalol infusion (data from heart #1). This run of reentry had a life span of 36 rotations, lasting from 578 to 2250 ms. Aa, mapped area. LAD indicates left anterior descending coronary artery. Ab–Ak: these phase maps show that this reentry first drifted to the border of mapped area (Ae), again into the RV (Af), and finally to the interventricular septum (Ag to Ak). Black circles indicate the core of reentry. Arrowheads indicate PSs. Al shows the trajectory of core, demonstrating a meandering nature. B, local optical tracings recorded from sites x and y (see panel Ab). C, the simultaneous pseudo-ECG and corresponding DF of 18.7 Hz. D, another 5 examples of the trajectory of core of non-stationary reentry (one from hearts #2–6, respectively). LS indicates the life span of reentry. Red colored trajectory indicates counterclockwise rotation. Blue colored trajectory indicates clockwise rotation.

Figure 5

A, effects of d,l-sotalol on APD, CT⁻¹ and WL restitutions. Data were obtained from heart #3 of protocol II. B, effects of d,l-sotalol on the maximum slope of APDR. Data were obtained from site b of heart #4 of protocol II. See text for details.