Age-associated changes in electrophysiologic remodeling: a potential contributor to initiation of atrial fibrillation.
OBJECTIVE
Although the incidence of atrial fibrillation (AF) increases with age, the cellular electrophysiological changes that render the atria of aged individuals more susceptible to AF remain poorly understood. We hypothesized that dispersion of atrial repolarization increases with aging, creating a substrate for initiation of AF.


METHODS
Four groups of dogs were studied: adult and old dogs in normal sinus rhythm (SR) and adult and old dogs with chronic AF (CAF) induced by rapid atrial pacing. In each dog, action potentials (AP) were recorded with microelectrodes from isolated endocardial preparations of four regions of right atrium and three regions of left atrium. Two indices of AP duration (APD) heterogeneity were obtained in each dog by calculating standard deviation (SD) and the coefficient of variation (COV=[SD/mean] x 100%).


RESULTS
In SR groups, APD averaged across all regions was significantly longer in old than in adult tissues. Both indices of APD heterogeneity were higher in old dogs in comparison to adult. At both ages, CAF was associated with significant APD shortening and a decrease in APD adaptation to rate. While CAF significantly increased both indices of APD heterogeneity in adult dogs, it significantly decreased them in old dogs.


CONCLUSIONS
The increase of spatial variability in repolarization in old atria may contribute to the initiation of AF in the aged. CAF-induced APD shortening and a decrease in APD adaptation appear to be important for the maintenance of sustained AF in both adult and old atria. The CAF-induced increase in dispersion of repolarization may be important for AF stabilization in adults, while previously reported fibrosis and slowed conduction of premature beats may be important in the old for both AF initiation during SR and subsequent stabilization of AF.
Anyukhovsky
Evgeny P
EP
Center for Molecular Therapeutics, Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Sosunov
Eugene A
EA
Chandra
Parag
P
Rosen
Tove S
TS
Boyden
Penelope A
PA
Danilo
Peter
P
Rosen
Michael R
MR
D000200:Action Potentials; D000375:Aging / Q000502:physiology*; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006325:Heart Atria; D008297:Male; D008839:Microelectrodes; D023421:Models, Animal