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

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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 ([Ca2+]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 [Ca2+]i was associated with fine AF whereas augmentation of [Ca2+]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 [Ca2+]i dynamics determine the degree to which AF is coarse or fine.