ELECTRICAL REMODELING IN ATRIAL-FIBRILLATION - TIME-COURSE AND MECHANISMS

Background Atrial fibrillation is self-perpetuating, suggestive that t he tachyarrhythmia causes electrophysiological changes that contribute to the progressive nature of the disease. In animal models, pacing-in duced rapid atrial rates result in sustained atrial fibrillation. This is mediated by shortening of refractory periods termed electrical rem odeling. The purpose of the present study was to characterize the time course of electrical remodeling and to define mechanisms of the pheno menon. Methods and Results Closed-chest dogs were anesthetized, pretre ated with atropine and propranolol. and subjected to 7 hours of atrial pacing at 800 bpm. The effective and absolute refractory periods (ARP and ERP) were measured during and after rapid pacing and transvenous endocardial biopsy specimens were examined using electron microscopy. Despite autonomic blockade and the absence of change in right atrial p ressure. persistent atrial tachycardia caused ARP and ERP to fall by > 10%. Electrical remodeling developed quickly, with more than half of t he phenemnon occurring during the first 30 minutes of high-rate pacing . Pretreatment with glibenclamide in doses sufficient to block the ATP -sensitive potassium current had no effect. Atrial electrical remodeli ng was blocked by verapamil and accentuated by hypercalcemia. Biopsy s pecimens from controls subjected to rapid pacing showed mitochondrial swelling consistent with calcium overload. Biopsies from verapamil-tre ated animals were normal. Conclusions Atrial electrical remodeling dev elops quickly, is progressive. and may be persistent. Shifts in autono mic tone, atrial stretch, or depletion of high-energy phosphates do no t contribute significantly to the phenomenon, Results of the study sug gest that atrial electrical remodeling is mediated by rate-induced int racellular calcium overload.