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the Cardiovascular Division, Department of Medicine, University of Pennsylvania and the Philadelphia VA Medical Center.
Correspondence to Lawrence H. Frame, MD, Cardiology Section (111C), Philadelphia VAMC, University and Woodland Aves, Philadelphia, PA 19104.
We hypothesized that drugs with rapid recovery kinetics from use-dependent sodium channel block could promote oscillatory termination of reentry by enhancing interval-dependent conduction. Mechanisms of termination were related to properties of the reentrant circuit. Nine adjustable reentrant preparations were used in which the canine atrial tricuspid ring was cut and then reconnected electronically by sensing activation on one side of the cut and pacing the other after an adjustable delay. The cycle length and diastolic interval during reentry were manipulated by changing this delay. Lidocaine (1.28x10-5 mol/L) significantly increased refractoriness (94±39 ms) and the slope of the conduction curve (-0.12±0.07) at the site of block during pacing. Lidocaine terminated sustained reentry by two mechanisms. Early termination resulted from increased cycle length oscillation and refractoriness (reproducible in each experiment) but only at short delays with short initial diastolic intervals. The range of delays showing this mechanism of termination was 100±48 ms. Increased cycle-length oscillation resulted from an increased slope of the conduction curve. In eight experiments, lidocaine terminated reentry by causing fixed block after 50 minutes of drug superfusion, which prevented reentry at all delays. Fixed block occurred at one of two vulnerable sites and was transiently reversed by acetylcholine. Termination due to refractory block occurred only when the initial diastolic interval was short, and termination due to fixed block developed when there was a susceptible region with a low safety factor for propagation. Fast recovery from sodium channel block promotes oscillatory termination by increasing the slope of the conduction curve.
Key Words: antiarrhythmic drug reentry use dependence lidocaine
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