Assessment of local atrial repolarization in a porcine acetylcholine model of atrial flutter and fibrillation

Abstract

Objectives - Progressive electrical alternans followed by conduction block and fibrillatory conduction have been suggested to precede disorganization of atrial flutter (Afl) to atrial fibrillation (AF). The purpose of the present study was to investigate patterns of local repolarization in the high and low right atrium to determine the site with pronounced propensity to action potential disorganization during Afl and AF. Methods - Combination pacing/recording contact monophasic action potential (MAP) catheters were utilized to evaluate repolarization from the upper and low atrial endocardium in 16 pigs. To induce sustained atrial flutter (Afl) or fibrillation (AF), programmed atrial stimulation was carried out prior to and during intravenous acetylcholine (ACh) infusion at a dosage rate of 2.7 mg/min. Atrial repolarization was measured at 30, 50, and 90% of total MAP duration. Results - Two main types of atrial MAPs were distinguished: MAPs originated from high atrial regions showing a prominent notch and longer duration and MAPs recorded from the lower atrium displaying a much slower slope of phase I repolarization and shorter duration. Control stimulation did not elicit any significant atrial tachyarrhythmias. After ACh all animals developed reproducibly induced sustained and non-sustained whole Afl or AF during programmed stimulation. A total of 40 sustained arrhythmia episodes were selected for evaluation: fourteen episodes of primary AF and 26 episodes of Afl. Whole Afl and AF in all animals were associated with MAPs of almost regular morphology in lower parts of atrium and disorganized activation in higher atrial regions. ACh significantly reduced (P < 0.001) both high and low atrial effective refractory periods as well as MAP duration determined at 30, 50, and 90% repolarization. Conclusions - ACh facilitated the induction of Afl more than AF in this experimental model. MAPs recorded from high atrial regions revealed discordant repolarization during Afl or AF, whereas low atrial MAPs maintained their baseline regular morphology. These findings may help expand knowledge about mechanisms underlying instability and perpetuation of these arrhythmias.