The inward rectifier current inhibitor PA-6 terminates atrial fibrillation and does not cause ventricular arrhythmias in goat and dog models.

ABSTRACT:

Background and purpose

The density of the inward rectifier current (I_K1 ) increases in atrial fibrillation (AF), shortening effective refractory period and thus promoting atrial re-entry. The synthetic compound pentamidine analogue 6 (PA-6) is a selective and potent I_K1 inhibitor. We tested PA-6 for anti-AF efficacy and potential proarrhythmia, using established models in large animals.

Experimental approach

PA-6 was applied i.v. in anaesthetized goats with rapid pacing-induced AF and anaesthetized dogs with chronic atrio-ventricular (AV) block. Electrophysiological and pharmacological parameters were determined.

Key results

PA-6 (2.5 mg·kg^-1 ·10 min^-1 ) induced cardioversion to sinus rhythm (SR) in 5/6 goats and prolonged A

SUBMITTER: Ji Y 

PROVIDER: S-EPMC5513871 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature