title: d-Sotalol terminates reentry by two mechanisms with different dependence on the duration of the excitable gap.
abstract: We used eight adjustable preparations in which the canine atrial tricuspid rings were cut and reconnected electronically by sensing activation on one side of the cut and pacing the other after an adjustable delay. A long delay resulted in a long cycle length (CL) and excitable gap (EG) during reentry. Decreasing delay decreased CL and EG. d-Sotalol (4 mg/l) significantly increased effective refractory period (ERP) and action potential duration with no effects on conduction time during constant 400-msec pacing. During reentry, d-sotalol increased action potential durations more than CLs, so it decreased diastolic intervals. It decreased EG by increasing ERP more than CL. Although d-sotalol increased action potential duration more at longer delays with longer CLs, showing reverse use-dependence, it terminated sustained tachycardias by increasing ERP only for the short delays when the initial EG was short. In 5 of 8 experiments, longer equilibration with d-sotalol produced fixed block at a vulnerable site, so reentry could not be induced at any delays. Fixed block could be transiently reversed by ACh and resolved after washout of d-sotalol. We conclude that d-sotalol terminated reentry by two mechanisms: 1) It terminated sustained reentry by increasing ERP when the initial EG was sufficiently short. 2) In some preparations, it caused fixed block at a vulnerable site, which prevented reentry regardless of the initial EG.
authors.affiliation: Cardiovascular Division, Department of Medicine, University of Pennsylvania, Philadelphia, USA.
authors.forename: H
authors.initials: H
authors.lastname: Fei
authors.forename: L H
authors.initials: LH
authors.lastname: Frame
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013015:Sotalol / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D013015:Sotalol