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


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.
Hsieh
Yu-Cheng
YC
Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
Horng
Tzyy-Leng
TL
Lin
Shien-Fong
SF
Lin
Tung-Chao
TC
Ting
Chih-Tai
CT
Wu
Tsu-Juey
TJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D011817:Rabbits; D013015:Sotalol / Q000494:pharmacology*; D017180:Tachycardia, Ventricular / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D013015:Sotalol