Differential effects of class I antiarrhythmic drugs on the guinea pig pulmonary vein myocardium: Inhibition of automatic activity correlates with blockade of a diastolic sodium current component

Inhibitory Effect of a Late Sodium Current Blocker, NCC-3902, on the Automaticity of the Guinea Pig Pulmonary Vein Myocardium

“…Flecainide, a class I antiarrhyth- mic used in the treatment of atrial fibrillation, was reported to have inhibitory activity on the pulmonary vein automaticity similar to the presently observed effects of NCC-3902, but with lower potency. 14) Flecainide significantly decreased the ventricular contractile force at 10 µM, which is the concentration with inhibitory effects on the pulmonary vein automaticity comparable to that of 1 µM NCC-3902. This indicates that the negative inotropic effect of flecainide cannot be ascribed to late I Na blockade, but may be the result of other effects such as blockade of peak I Na , I Ca,L , I Kr , and the ryanodine receptor.…”

“…One of the reasons for this may be insufficient inhibition of the arrhythmogenic trigger including those originating in the pulmonary vein myocardium. 5) Although some of the existing class I antiarrhythmics have inhibitory effects on late I Na , 14) their potency is limited and, on the other hand, they often show unwanted cardio-suppressive effects through inhibitory effects on other ionic mechanisms such as the Ltype Ca 2+ channel current. 22,23) The present study showed that NCC-3902, a selective late I Na blocker, inhibited spontaneous firing of action potentials in the pulmonary vein myocardium, the main trigger of atrial fibrillation.…”

“…All experiments with isolated guinea pig myocardium were performed with methods substantially the same as those in our previous studies. 7,8,13,14,[16][17][18][19] This study was approved by the Animal Care and User Committee of Toho University (21-55-362).…”

“…Agents with inhibitory effects on late I Na inhibited the pacemaker depolarization slope and automatic activity. 13,14) Flecainide and propafenone, drugs that are often used for the treatment of atrial fibrillation, also showed such effects. However, the potency of these drugs on late I Na was moderate, and to what extent the effect contributes to their therapeutic potential was unclear.…”