Role of Repolarization Restitution in the Development of Coarse and Fine Atrial Fibrillation in the Isolated Canine Right Atria

Abstract

Introduction: Although the role of action potential duration restitution (APD-R) in the initiation and maintenance of ventricular fibrillation (VF) has been the subject of numerous investigations, its role in the generation of atrial fibrillation (AF) is less well studied. The cellular and ionic basis for coarse versus fine AF is not well delineated. Methods and Results: We measured APD-R during acetylcholine-mediated AF as well as during pacing (standard and dynamic protocols) in crista teriminalis, pectinate muscle, superior vena cava, and appendage of isolated canine arterially perfused right atria (n = 15). Transmembrane action potential (TAP), pseudo-ECG, and isometric tension development were simultaneously recorded. Acetylcholine flattened APD-R measured by both standard and dynamic protocols, but promoted induction of AF. AF was initially coarse, converting to fine within 3-15 minutes of AF. Coarse, but not fine AF was associated with dramatic fluctuations in tension development, reflecting wide variations in intracellular calcium activity ([Ca 2+ ] i ). During coarse AF, APD-R data displayed a cloud-like distribution pattern, with a wide range of maximum APD-R slope (from 1.21 to 0.35). A maximum APD-R slope >1 was observed only in crista terminalis (3/10). The APD-R relationship was relatively linear and flat during fine AF. Reduction of [Ca 2+ ] i was associated with fine AF whereas augmentation of [Ca 2+ ] i with coarse AF. Conclusions: Our data indicate that while APD-R may have a limited role in the maintenance of coarse AF, it is unlikely to contribute to the maintenance of fine AF and that [Ca 2+ ] i dynamics determine the degree to which AF is coarse or fine.

Atrial-selective inhibition of sodium-channel current by Wenxin Keli is effective in suppressing atrial fibrillation

“…3, 13 Wenxin Keli (5 g/L) prevented the induction of persistent AF in 100% of preparations tested (6/6 atria) (Fig. 6).…”

Mechanisms of Human Atrial Fibrillation Initiation

“…20 Our findings may differ for several reasons: (a) we examined AF in patients with clinical atrial remodeling versus a canine acetylcholine-AF model, and (b) we examined the mechanisms of AF initiation, rather than those that perpetuate AF. Interestingly, recent animal studies also support the role of steep APD restitution in AF initiation from rapid pacing.…”

Ranolazine Exerts Potent Effects on Atrial Electrical Properties and Abbreviates Atrial Fibrillation Duration in the Intact Porcine Heart

“…The median change across all three atrial sites was 45 (29-50) ms compared to control (P < 0.05, n = 6) at PCL of 400 ms and testing at twice the diastolic threshold. The drug also caused an increase in the ERP of the RV endocardium of 28 (24-34) ms (P < 0.01, n = 6) but this effect was of lesser magnitude than that observed in the atria (P = 0.03 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) ms at PCL of 300 ms was greater in the four animals in which the refractory period measurements were made at 2 different PCLs, but this finding did not reach statistical significance (P = 0.09). There was no significant change in the dispersion of ERP across the atrial sites before and after ranolazine.…”

“…This model was developed in light of the importance of the role of this neurotransmitter in AF in humans and extensive evidence regarding the putative clinically relevant mechanisms of AF involving not only atrial tissue but also ganglionic plexi and pulmonary veins. [7][8][9][10][11] …”