Effects of flecainide and quinidine on human atrial action potentials : role of rate-dependence and comparison with guinea pig, rabbit, and dog tissues

摘要: Flecainide and other class IC antiarrhythmic drugs are effective in the prevention termination of atrial fibrillation, but mechanism this action is unknown. To gain insights into potential cellular mechanisms, we evaluated response human potentials to equimolar therapeutic concentrations flecainide quinidine compared that guinea pig, rabbit, dog atria. Both compounds reduced Vmax more as activation rate increased, was potent than had slower kinetics. The rate-dependence reduction similar for all species, tissue sensitive tested. In contrast changes Vmax, drug-induced alterations duration showed opposite two drugs. Quinidine increased 95% repolarization (APD95) atria by 33 +/- 7% (mean SD) at a cycle length 1,000 msec, effect decreased, 12 4% (p less 0.001) 300 msec. APD95 (by 6 3%) much its faster pacing, 27 12% msec 35 8% shortest 1:1 length. rate-dependent APD qualitatively quantitatively different among species. Human greatest frequency-dependent drug effects on repolarization, followed from dogs rabbits. Guinea pig least (and statistically nonsignificant) APD. Drug-induced refractoriness paralleled those We conclude that: 1) both increase with rate-dependence, 2) enhanced rapid rates typical 3) animal tissues may differ importantly their sensitivity salutary fibrillation be due enhancement characteristic arrhythmia.