Intravenous administration of NIP-142 (3 mg/kg) terminated vagally induced atrial fibrillation in 5 of 6 dogs and anatomically induced atrial flutter in all 6 dogs.
Does the novel Class III antiarrhythmic agent NIP-142 terminate and prevent reinitiation of atrial fibrillation and flutter in a canine model?
The novel Class III antiarrhythmic agent NIP-142 effectively terminates and prevents reinitiation of atrial fibrillation and flutter in canine models by prolonging atrial refractoriness.
The effects of a new benzopyran derivative, NIP-142, on atrial fibrillation (AF) and flutter (AFL) and on electrophysiological variables were studied in the dog. NIP-142 (3mg/kg) was administered intravenously to pentobarbital-anesthetized beagles during vagally-induced AF and during AFL induced after placement of an intercaval crush. Isolated canine atrial tissues were studied using standard microelectrode technique. NIP-142 terminated AF in 5 of 6 dogs after an increase in fibrillation cycle length (CL) and prevented reinitiation of AF in all 6 dogs. NIP-142 terminated AFL in all 6 dogs without any appreciable change in flutter CL, and prevented reinitiation of AFL in all 6 dogs. NIP-142 prolonged atrial effective refractory periods (11+/-5%, 3+/-3%, 12+/-3%, and 10+/-5% from the baseline value at basic CLs of 150, 200, 300, and 350ms, respectively) without changes in intraatrial conduction time. The prolongation of the atrial effective refractory period was greater in the presence of vagal stimulation. NIP-142 decreased action potential phase-1 notch and increased phase-2 plateau height without making any changes in the action potential duration, although it did reverse carbachol-induced shortening of the action potential duration. In conclusion, NIP-142 is effective in treating AFL and vagally-induced AF by prolonging atrial refractoriness.
Nagasawa et al. (Tue,) conducted a other in Atrial fibrillation and atrial flutter (induced) (n=33). NIP-142 vs. Baseline was evaluated on Termination of vagally induced atrial fibrillation. Intravenous administration of NIP-142 (3 mg/kg) terminated vagally induced atrial fibrillation in 5 of 6 dogs and anatomically induced atrial flutter in all 6 dogs.