title: Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1.
abstract: Studies on patients and large animal models suggest the importance of atrial fibrosis in the development of atrial fibrillation (AF). To investigate whether increased fibrosis is sufficient to produce a substrate for AF, we have studied cardiac electrophysiology (EP) and inducibility of atrial arrhythmias in MHC-TGFcys33ser transgenic mice (Tx), which have increased fibrosis in the atrium but not in the ventricles. In anesthetized mice, wild-type (Wt) and Tx did not show significant differences in surface ECG parameters. With transesophageal atrial pacing, no significant differences were observed in EP parameters, except for a significant decrease in corrected sinus node recovery time in Tx mice. Burst pacing induced AF in 14 of 29 Tx mice, whereas AF was not induced in Wt littermates (P<0.01). In Langendorff perfused hearts, atrial conduction was studied using a 16-electrode array. Epicardial conduction velocity was significantly decreased in the Tx RA compared with the Wt RA. In the Tx LA, conduction velocity was not significantly different from Wt, but conduction was more heterogeneous. Action potential characteristics recorded with intracellular microelectrodes did not reveal differences between Wt and Tx mice in either atrium. Thus, in this transgenic mouse model, selective atrial fibrosis is sufficient to increase AF inducibility.
authors.affiliation: Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Ind, USA.
authors.forename: Sander
authors.initials: S
authors.lastname: Verheule
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sato
authors.forename: Thomas
authors.initials: T
authors.lastname: Everett
authors.forename: Steven K
authors.initials: SK
authors.lastname: Engle
authors.forename: Dan
authors.initials: D
authors.lastname: Otten
authors.forename: Michael
authors.initials: M
authors.lastname: Rubart-von der Lohe
authors.forename: Hisako O
authors.initials: HO
authors.lastname: Nakajima
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Nakajima
authors.forename: Loren J
authors.initials: LJ
authors.lastname: Field
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Olgin
mesh_terms: D000200:Action Potentials; D019943:Amino Acid Substitution; D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D005355:Fibrosis; D020022:Genetic Predisposition to Disease; D006325:Heart Atria / Q000473:pathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1
chemical_list: C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1